Análise de macrófagos M1 e M2 em modelo experimental de leishmaniose cutânea submetido à terapia fotodinâmica associada ao ácido 5-aminolevulínico

Detalhes bibliográficos
Autor(a) principal: SILVA, Mona Lisa Fabiana
Data de Publicação: 2015
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFTM
Texto Completo: http://bdtd.uftm.edu.br/handle/tede/266
Resumo: Introdução: A leishmaniose é uma doença infecciosa causada por parasitas do gênero Leishmania. Sua forma cutânea é causada pela L. major no velho mundo e pela Leishmania braziliensis nas Américas. Devido a sua localização, a Terapia Fotodinâmica pode representar uma abordagem terapêutica interessante. Os macrófagos são as células hospedeiras da Leishmania no homem e podem ser classificados como macrófagos M1 ou M2 dependendo do padrão de citocinas secretado. Neste estudo, avaliamos o perfil de macrófagos do tipo1 e tipo 2, a efetividade da Terapia Fotodinâmica (TFD) utilizando ao ácido aminolevulínico (ALA) no tratamento da leishmaniose cutânea (LC) e os níveis de Heme oxigenase 1 (HO-1) em modelo experimental de leishmaniose tratado com ALA-TFD. Métodos: Camundongos BALB/c machos com quatro semanas foram infectados nas patas com 1x106 formas amastigotas de Leishmania braziliensis, após 4 semanas os camundongos foram tratados com ALA, LUZ ou com ALA-TFD. Foi avaliada ex vivo a expressão dos marcadores mRNA interleucina (IL)-10 e Arginase-1 para identificação de macrófagos M2, TNF-α e iNOS para M1 e HO-1 no local da infecção. Resultados: O número de parasitas diminuiu significativamente nos grupos com TFD quando comparado aos demais. Os Níveis de iNOS foram maiores, não significativamente, no grupo TFD. Não houve diferença na expressão dos demais produtos testados. Conclusão: A morte do parasita não parece ser mediada pela modulação de macrófagos M1 ou M2 neste modelo experimental de leishmaniose tratado com ALA-PDT. A terapia reduz significativamente a carga parasitária in vivo sem a eliminação completa do parasita. O aumento de iNOS sugere a sua participação nos mecanismo microbicidas ativados por ALAPDT.
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spelling Análise de macrófagos M1 e M2 em modelo experimental de leishmaniose cutânea submetido à terapia fotodinâmica associada ao ácido 5-aminolevulínicoAnalysis of macrophage types M1 and M2 in an experimental model of cutaneous leishmaniasis treated with photodynamic therapy associated with 5-aminolevulinic acidTerapia FotodinâmicaALA-TFDLeishmania braziliensisácido 5- aminolevulinicoMacrófagosPhotodynamic therapyALA-PDTLeishmania braziliensis5-aminolevulinic acidMacrophagesParasitologiaIntrodução: A leishmaniose é uma doença infecciosa causada por parasitas do gênero Leishmania. Sua forma cutânea é causada pela L. major no velho mundo e pela Leishmania braziliensis nas Américas. Devido a sua localização, a Terapia Fotodinâmica pode representar uma abordagem terapêutica interessante. Os macrófagos são as células hospedeiras da Leishmania no homem e podem ser classificados como macrófagos M1 ou M2 dependendo do padrão de citocinas secretado. Neste estudo, avaliamos o perfil de macrófagos do tipo1 e tipo 2, a efetividade da Terapia Fotodinâmica (TFD) utilizando ao ácido aminolevulínico (ALA) no tratamento da leishmaniose cutânea (LC) e os níveis de Heme oxigenase 1 (HO-1) em modelo experimental de leishmaniose tratado com ALA-TFD. Métodos: Camundongos BALB/c machos com quatro semanas foram infectados nas patas com 1x106 formas amastigotas de Leishmania braziliensis, após 4 semanas os camundongos foram tratados com ALA, LUZ ou com ALA-TFD. Foi avaliada ex vivo a expressão dos marcadores mRNA interleucina (IL)-10 e Arginase-1 para identificação de macrófagos M2, TNF-α e iNOS para M1 e HO-1 no local da infecção. Resultados: O número de parasitas diminuiu significativamente nos grupos com TFD quando comparado aos demais. Os Níveis de iNOS foram maiores, não significativamente, no grupo TFD. Não houve diferença na expressão dos demais produtos testados. Conclusão: A morte do parasita não parece ser mediada pela modulação de macrófagos M1 ou M2 neste modelo experimental de leishmaniose tratado com ALA-PDT. A terapia reduz significativamente a carga parasitária in vivo sem a eliminação completa do parasita. O aumento de iNOS sugere a sua participação nos mecanismo microbicidas ativados por ALAPDT.Introduction: Leishmaniasis is an infectious disease caused by parasites of the genus Leishmania. Cutaneous leishmaniasis (CL) is caused by L. major in the old world and by L. braziliensis in the Americas. Considering the targeted organs, photodynamic therapy (PDT) may constitute a valuable therapeutic intervention. Macrophages are the host cells of Leishmania in mamals and may be classified into type M1 or M2 depending on the pattern of activation. In this study, we evaluated the profile of macrophage and the effectiveness of PDT for the treatment of experimental CL. Methods: BALB/c mice were infected in the foot pad with 1 x 106 amastigotes of L. braziliensis and treated with aminolevulinic acid (ALA), visible light, or ALA-PDT. The ex vivo mRNA expression levels of interleukin-10 and arginase-1, and TNF-α and induced nitric oxide synthase (iNOS) was quantitated for the identification of M2 and M1 macrophages, respectively. Results: The parasite load decreased significantly in the groups treated with PDT compared with the other groups. The iNOS levels were higher in the group treated with PDT, but the difference was not significant. Moreover, no significant difference was observed in the expression of the other markers evaluated. Conclusion: Parasite death does not appear to be mediated by the modulation of M1 or M2 macrophages in this experimental model of leishmaniasis treated with ALA-PDT. PDT significantly decreased the parasite load in vivo but did not eliminate parasitism. The increase in the iNOS levels suggests it might participate in the antimicrobial mechanisms triggered by ALA-PDT.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESFundação de Amparo a Pesquisa do Estado de Minas Gerais - FAPEMIGUniversidade Federal do Triângulo MineiroInstituto de Ciências da Saúde - ICS::Curso de MedicinaBrasilUFTMCurso de Pós-Graduação em Ciências Fisiológicas - Parasitologia, Imunologia e MicrobiologiaRODRIGUES JUNIOR, Virmondes45813493620http://lattes.cnpq.br/8909243237236516PAULINO, Tony de Paiva92251048634http://lattes.cnpq.br/3179978364259887SILVA, Mona Lisa Fabiana2016-07-14T17:25:41Z2015-06-29info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfSILVA, Mona Lisa Fabiana. Análise de macrófagos M1 e M2 em modelo experimental de leishmaniose cutânea submetido à terapia fotodinâmica associada ao ácido 5-aminolevulínico. 2015. 43f. Dissertação (Mestrado em Ciências Fisiológicas) - Curso de Pós-Graduação em Ciências Fisiológicas, Universidade Federal do Triângulo Mineiro, Uberaba, 2015.http://bdtd.uftm.edu.br/handle/tede/266porABEBE, T. et al. Local increase of arginase activity in lesions of patients with cutaneous leishmaniasis in ethiopia. PLoS Neglected Tropical Diseases, v. 6, n. 6, p. 1–10, 2012. ACKROYD, R. et al. The history of photodetection and photodynamic therapy. Photochemistry and photobiology, v. 74, n. 5, p. 656–669, 2001. AGOSTINIS, P. et al. Photodynamic Therapy of Cancer : An Update. American Cancer Society, v. 61, p. 250–281, 2011. AGOSTINIS, P. et al. Photodynamic Therapy of Cancer: an Update. v. 61, n. 4, p. 250–281, 2012. AKILOV, O. E. et al. Parasiticidal effect of ??-aminolevulinic acid-based photodynamic therapy for cutaneous leishmaniasis is indirect and mediated through the killing of the host cells. Experimental Dermatology, v. 16, n. 8, p. 651–660, 2007. ALVES, J. M. P. et al. Identification and phylogenetic analysis of heme synthesis genes in trypanosomatids and their bacterial endosymbionts. PLoS ONE, v. 6, n. 8, 2011. ASILIAN, A.; DAVAMI, M. Comparison between the efficacy of photodynamic therapy and topical paromomycin in the treatment of Old World cutaneous leishmaniasis: A placebocontrolled, randomized clinical trial. Clinical and Experimental Dermatology, v. 31, n. 5, p. 634–637, 2006. AULER, H., BANZER, G. Untersuchungen Uber die Rolle der Porphyrine bei geschwulstkranken Menschen und Tieren. Cancer Research Clinical Oncology, v. 53, n. 65, p. 65–68, 1942. AWASTHI, A.; KUMAR, M. R.; SAHA, B. Immune Response to Leishmania infecction. Indian J. Med. Res., v. 119, n. June, p. 238–258, 2004. BABIOR, B. M. Phagocytes and oxidative stress. American Journal of Medicine, v. 109, n. 1, p. 33–44, 2000. BABIOR, B. M.; KIPNES, R. S.; CUMVU, J. T. The production by leukocytes of superoxide, a potencial bactericidal agent. v. 52, n. March, p. 741–744, 1973. BARRAL, A et al. Transforming growth factor beta as a virulence mechanism for Leishmania braziliensis. Proceedings of the National Academy of Sciences of the United States of America, v. 90, n. 8, p. 3442–3446, 1993. BASANO, S. D. A.; CAMARGO, L. M. A. Leishmaniose tegumentar americana: histórico, epidemiologia e perspectivas de controle. Revista Brasileira de Epidemiologia, v. 7, n. 3, p. 328–337, 2004. BEGNAMI, M. D. F. S. et al. Análise imuno-histoquímica das sintases do óxido nítrico em adenocarcinomas gástricos. Jornal Brasileiro de Patologia e Medicina Laboratorial, v. 40, n. 5, p. 351–357, 2004. BELKAID, Y.; PICCIRILLO, C. A; MENDEZ, S. CD4+ CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature, v. 420, n. September, p. 633–637, 2002. BERMAN, J. D. Human leishmaniasis: clinical, diagnostic, and chemotherapeutic developments in the last 10 years. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, v. 24, n. 4, p. 684–703, 1997. BIEDERMANN, T.; RÖCKEN, M.; CARBALLIDO, J. M. TH1 and TH2 lymphocyte development and regulation of TH cell-mediated immune responses of the skin. The journal of investigative dermatology. Symposium proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research, v. 9, n. 1, p. 5– 14, 2004. BOGDAN, C.; RÖLLINGHOFF, M.; DIEFENBACH, A. The role of nitric oxide in innate immunity. Immunological reviews, v. 173, n. 1, p. 17–26, 2000a. BOGDAN, C.; RÖLLINGHOFF, M.; DIEFENBACH, A. Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity. Current Opinion in Immunology, v. 12, n. 1, p. 64–76, 2000b. BONNETT, R. Photosensitizers of the porphyrin and phthalocyanine series for photodynamic therapy. Chemical Society reviews, v. 24, n. 1, p. 19–33, 1995. BRASIL. Ministério da Saúde. Manual de Vigilância da Leishmaniose Tegumentar Americana / Ministério da Saúde, Secretaria de Vigilância em Saúde, Departamento de Vigilância Epidemiológica. – 2. ed. – Brasília : Editora do Ministério da Saúde, p.187, 2007. BRASIL. Ministério da Saúde. Manual de Vigilância da Leishmaniose Tegumentar Americana / Ministério da Saúde, Secretaria de Vigilância em Saúde, Departamento de Vigilância Epidemiológica. – 2. ed. – Brasília : Editora do Ministério da Saúde, p.180, 2010. BREUSING, N. et al. Light-induced cytotoxicity after aminolevulinic acid treatment is mediated by heme and not by iron. Journal of Photochemistry and Photobiology B: Biology, v. 99, n. 1, p. 36–43, 2010. BRITO, M. E. F. et al. Species diversity of Leishmania (Viannia) parasites circulating in an endemic area for cutaneous leishmaniasis located in the Atlantic rainforest region of northeastern Brazil. Tropical Medicine and International Health, v. 14, n. 10, p. 1278– 1286, 2009. C. FALCÃO, S. et al. The presence of Tregs does not preclude immunity to reinfection with Leishmania braziliensis. International Journal for Parasitology, v. 42, n. 8, p. 771–780, 2012. CAMPOS-NETO, A. What about Th1 / Th2 in cutaneous leishmaniasis vaccine discovery ? Brazilian Journal Of Medical And Biological Research, v. 38, p. 979–984, 2005. CASTANO, A.; MROZ, P.; HAMBLIN, M. Photodynamic therapy and anti-tumour immunity. Nature Reviews Cancer, v. 6, n. 7, p. 535–545, 2006. CEDERBAUM, S. D. et al. Arginases I and II: Do their functions overlap? Molecular Genetics and Metabolism, v. 81, n. SUPPL., p. 38–44, 2004. CORREA, M. A. D., LOPEZ, M. R. Alternative macrophage activation: the diversity of one cell involved in innate immunity in response to it’s environmental complexity. Immunology, v. 26, n. 2, p. 73–86, 2007. COSTA, D. L. et al. Tr-1-Like CD4+CD25-CD127-/lowFOXP3- Cells Are the Main Source of Interleukin 10 in Patients With Cutaneous Leishmaniasis Due to Leishmania braziliensis. Journal of Infectious Diseases, v. 211, n. 5, p. 708–718, 2014. COSTA, J. M. L. et al. Clinical Modalites, Diagnosis e Therapeutic Aproach of the Tegumentary Leishmaniasis in Brazil. Gazeta Medica da Bahia, v. 79, n. V, p. 70–83, 2009. COUPER, K. N.; BLOUNT, D. G.; RILEY, E. M. IL-10: the master regulator of immunity to infection. Journal of immunology, v. 180, n. 9, p. 5771–5777, 2008. CROFT, S. L.; SUNDAR, S.; FAIRLAMB, A. H. Drug Resistance in Leishmaniasis. Society, v. 19, n. 1, p. 111–126, 2006. CRUZ, E. DE M. Inibição da arginase de Leishmania por frações do extrato etanólico de Cecropia pachystachya. FUNDAÇÃO OSWALDO CRUZ CENTRO DE PESQUISAS GONÇALO MONIZ, 2011. DA SILVA, M. F. L. et al. Leishmania amazonensis arginase compartmentalization in the glycosome is important for parasite infectivity. PLoS ONE, v. 7, n. 3, 2012. DANIELL, M. D., HILL, J. S. A history of photodynamic therapy. Australian and New Zealand Journal of Surgery, v. 61, n. 5, p. 340–348, 1991. DESJARDINS, M.; DESCOTEAUX, A. Inhibition of phagolysosomal biogenesis by the Leishmania lipophosphoglycan. The Journal of experimental medicine, v. 185, n. 12, p. 2061–2068, 1997. DESJEUX, P. Leishmaniasis: Public Health Aspects and Control. Clinics in Dermatology, v. 14, n. 5, p. 417–423, 1996. DOMINGOS, P. L. B. et al. OX40+ T lymphocytes and IFN-γ are associated with American tegumentary leishmaniasis pathogenesis. Anais brasileiros de dermatologia, v. 87, n. 6, p. 851–5, 2012. DUPASQUIER, M. et al. The dermal microenvironment induces the expression of the alternative activation marker CD301/mMGL in mononuclear phagocytes, independent of IL- 4/IL-13 signaling. Journal of leukocyte biology, v. 80, n. 4, p. 838–849, 2006. DUSSE, L. M. S. A.; VIEIRA, L. M.; CARVALHO, M. G. Revisão sobre óxido nítrico; Nitric oxide revision. J. bras. patol. med. lab, v. 39, n. 4, p. 343–350, 2003. EL-ON, J.; BRADLEY, D. J.; FREEMAN, J. C. Leishmania donovani: action of excreted factor on hydrolytic enzyme activity of macrophages from mice with genetically different resistance to infection. Experimental parasitology, v. 49, n. 2, p. 167–174, 1980. ENGWERDA, C. R.; ATO, M.; KAYE, P. M. Macrophages, pathology and parasite persistence in experimental visceral leishmaniasis. Trends in Parasitology, v. 20, n. 11, p. 524–530, 2004. ENK, C. D. et al. [Cutaneous leishmaniasis]. Hautarzt, v. 54, n. 6, p. 506–512, 2003. FARAH, F. S.; SAMRA, S. A; NUWAYRI-SALTI, N. The role of the macrophage in cutaneous leishmaniasis. Immunology, v. 29, n. 4, p. 755–764, 1975. FERREIRA, A. et al. A central role for free heme in the pathogenesis of severe malaria: The missing link? Journal of Molecular Medicine, v. 86, n. 10, p. 1097–1111, 2008. FOOTE, C. S. Mechanisms of Photosensitized Oxidation. Sciences-New York, v. 162, n. 3857, p. 963–970, 1968. FORATTINI, O. P. Nota sobre o encontro de Leishmania em roedores silvestres de zona endêmica de leishmaniose no Estado de São Paulo, Brasil. Revista paulista de Medicina, v. 53, n. 2, p. 155, 1958. FRANK, J. et al. Inhibition of heme oxygenase-1 increases responsiveness of melanoma cells to ALA-based photodynamic therapy. International Journal of Oncology, v. 31, n. 6, p. 1539–1545, 2007. FRIES, D. S., FAIRLAMB, A. H. Antiprotozoal agents. 6th. ed. New York: [s.n.]. FURUSAWA, G. P.; BORGES, M. F. Colaboração Para O Conhecimento Do Histórico Da Leishmaniose Tegumentar Americana No Brasil: Possíveis Casos Entre Escravos Na Vila De Vassouras-Rj, Nos Anos 1820 a 1880. Revista de Patologia Tropical, v. 43, n. 1, p. 7–25, 2014. FURUYAMA, K.; KANEKO, K.; VARGAS, P. D. Heme as a magnificent molecule with multiple missions: heme determines its own fate and governs cellular homeostasis. The Tohoku journal of experimental medicine, v. 213, n. 1, p. 1–16, 2007. GARDLO, K. et al. Treatment of cutaneous leishmaniasis by photodynamic therapy. Journal of the American Academy of Dermatology, v. 48, n. 6, p. 893–896, 2003. GARDLO, K. et al. Photodynamische therapie bei kutaner leishmaniose: Eine viel versprechende neue therapiemodalit. Hautarzt, v. 55, n. 4, p. 381–383, 2004. GHAFFARIFAR, F. et al. Photodynamic therapy as a new treatment of cutaneous leishmaniasis. Eastern Mediterranean health journal = La revue de santé de la Méditerranée orientale = al-Majallah al-ṣiḥḥīyah li-sharq al-mutawassiṭ, v. 12, n. 6, p. 902–8, 2006. GOBERT, A. P. et al. L-arginine availability modulates local nitric oxide production and parasite killing in experimental trypanosomiasis. Infection and Immunity, v. 68, n. 8, p. 4653–4657, 2000. GONTIJO, B.; DE CARVALHO, M. D. L. R. Leishmaniose tegumentar Americana. Revista da Sociedade Brasileira de Medicina Tropical, v. 36, n. 1, p. 71–80, 2003. GONTIJO, C. M. F.; MELO, M. N. Leishmaniose visceral no Brasil: quadro atual, desafios e perspectivas. Revista Brasileira de Epidemiologia, v. 7, n. 3, p. 338–349, 2004. GORDON, S.; MARTINEZ, F. O. Alternative activation of macrophages: Mechanism and functions. Immunity, v. 32, n. 5, p. 593–604, 2010. GORMAN, A. et al. In vitro demonstration of the heavy-atom effect for photodynamic therapy. Journal of the American Chemical Society, v. 126, n. 34, p. 10619–10631, 2004. GREEN, S. J., MELTZER, M. S., HIBBS JR, J. B., NACY, C. A. Activated macrophages destroy intracelular Leishmania major amastigotes by L-arginine-dependent killing mechanism. The journal of immunology, v. 144, n. 1, p. 278–283, 1990. GREVELINK, S. A; LEMER, E. A. Leishmaniasis. Jounal of the american academy of dermatology, v. 34, n. 2, p. 257–272, 1996. GRODY, W. W. et al. Differential expression of the two human arginase genes in hyperargininemia. Enzymatic, pathologic, and molecular analysis. Journal of Clinical Investigation, v. 83, n. 2, p. 602–609, 1989. GURUVAYOORAPPAN, C. Tumor versus tumor-associated macrophages: how hot is the link? Integrative cancer therapies, v. 7, n. 2, p. 90–95, 2008. HANDMAN, E. Leishmaniasis : Current Status of Vaccine Development Leishmaniasis : Current Status of Vaccine Development. Clinical Microbiology Reviews, v. 14, n. 2, p. 229– 243, 2001. HANDMAN, E.; BULLEN, D. V. R. Interaction of Leishmania with the host macrophage. Trends in Parasitology, v. 18, n. 8, p. 332–334, 2002. HEINZEL, FP, SCHOENHAUT, DS, RERKO, R. M, ROSSER, L., GATELY, M. K. Recombinant Interleukin 12 Cures Mice Infected with Leishmania major. The Journal of experimental medicine, v. 177, n. 5, p. 1505–1509, 1993. HESSE, M. et al. Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of L-arginine metabolism. Journal of immunology, v. 167, n. 11, p. 6533–6544, 2001. HRYHORENKO, E. A et al. Antigen specific and nonspecific modulation of the immune response by aminolevulinic acid based photodynamic therapy. Immunopharmacology, v. 40, n. 3, p. 231–240, 1998. IBANEZ SIMPLICIO, F.; MAIONCHI, F.; HIOKA, N. Terapia fotodinâmica: Aspectos farmacológicos, aplicações e avanços recentes no desenvolvimento de medicamentos. Quimica Nova, v. 25, n. 5, p. 801–807, 2002. ISSA, M. C. A.; MANELA-AZULAY, M. Photodynamic therapy: a review of the literature and image documentation. Anais brasileiros de dermatologia, v. 85, n. 4, p. 501–511, 2010. JACOBINA, R. R.; GELMAN, E. A. Juliano Moreira and the Gazeta Medica da Bahia. Historia, ciencias, saude--Manguinhos, v. 15, n. 4, p. 1077–1097, 2008. JENKINSON, C. P.; GRODY, W. W.; CEDERBAUM, S. D. Comparative properties of arginases. Comparative Biochemistry and Physiology - B Biochemistry and Molecular Biology, v. 114, n. 1, p. 107–132, 1996. JORI, G. Tumour photosensitizers: Approaches to enhance the selectivity and efficiency of photodynamic therapy. Journal of Photochemistry and Photobiology B: Biology, v. 36, n. 2, p. 87–93, 1996. KAYE, P.; SCOTT, P. Leishmaniasis: complexity at the host-pathogen interface. Nature reviews. Microbiology, v. 9, n. 8, p. 604–615, 2011. KENNEDY, J. Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. Journal of Photochemistry and Photobiology B: Biology, v. 6, p. 143–148, 1990. KESSEL, D. et al. Modes of photodynamic vs. sonodynamic cytotoxicity. Journal of photochemistry and photobiology. B, Biology, v. 28, n. 3, p. 219–221, 1995. KHARKWAL, G. B. et al. Photodynamic Therapy for Infections: Clinical Applications. v. 43, n. 7, p. 755–767, 2012. KIM, C. H. et al. Synergistic effects of 5-aminolevulinic acid based photodynamic therapy and celecoxib via oxidative stress in human cholangiocarcinoma cells. International Journal of Nanomedicine, v. 8, p. 2173–2186, 2013. KOPF, M., BROMBACHER, F. KOHLER, G., KIENZLE, G.; WIDMANN, K., LEFRANG, K.; HUMBORG, C., LEDERMANN, B., SOLBACH, W. IL-4-deficient Balb/c Mice Resist Infection with Leishmania major. Immunological reviews, v. 184, n. 3, p. 1127–1136, 1996. KOŘENÝ, L.; LUKEŠ, J.; OBORNÍK, M. Evolution of the haem synthetic pathway in kinetoplastid flagellates: An essential pathway that is not essential after all? International Journal for Parasitology, v. 40, n. 2, p. 149–156, 2010. LAUNOIS, P., LOUIS, J. A., MILON, G. The fate and persistence of Leishmania major in mice of different genetic backgrounds: an example of exploitation of the immune system by intracellular parasites. Parasitology, v. 115, p. 25–32, 1997. LEE, T.-S.; TSAI, H.-L.; CHAU, L.-Y. Induction of heme oxygenase-1 expression in murine macrophages is essential for the anti-inflammatory effect of low dose 15-deoxy-Delta 12,14- prostaglandin J2. The Journal of biological chemistry, v. 278, n. 21, p. 19325–19330, 2003. LETTERIO, J. J.; ROBERTS, A B. Regulation of immune responses by TGF-beta. Annual review of immunology, v. 16, n. 1, p. 137–161, 1998. LIEW, F. Y. et al. Tumour necrosis factor (TNF alpha) in leishmaniasis. I. TNF alpha mediates host protection against cutaneous leishmaniasis. Immunology, v. 69, n. 4, p. 570– 573, 1990. LIEW, F. Y.; WEI, X. Q.; PROUDFOOT, L. Cytokines and nitric oxide as effector molecules against parasitic infections. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, v. 352, n. 1359, p. 1311–1315, 1997. LIMA, M. S. D. C. et al. Identificação de espécies de Leishmania isoladas de casos humanos em Mato Grosso do Sul por meio da reação em cadeia da polimerase. Revista da Sociedade Brasileira de Medicina Tropical, v. 42, n. 3, p. 303–308, 2009. LIU, D.; UZONNA, J. E. The early interaction of Leishmania with macrophages and dendritic cells and its influence on the host immune response. Frontiers in Cellular and Infection Microbiology, v. 2, n. June, p. 1–8, 2012. LU, J. et al. Discrete functions of M2a and M2c macrophage subsets determine their relative efficacy in treating chronic kidney disease. Kidney international, v. 84, n. 4, p. 745–55, 2013. LUZ, N. F. Papel da proteína heme oxigenase 1 na infecção de macrófagos por Leishmania chagasi. [s.l.] Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz, 2011. LUZ, N. F. et al. Heme oxygenase-1 promotes the persistence of Leishmania chagasi infection. Journal of immunology (Baltimore, Md. : 1950), v. 188, n. 9, p. 4460–7, 2012. MARCONDES, C. B. et al. A survey of visceral leishmaniasis in dogs from Santa Maria and neighbouring municipalities, State of Rio Grande do Sul. Revista da Sociedade Brasileira de Medicina Tropical, v. 36, n. 4, p. 499–501, 2003. MARQUES, S. A. Leishmaniose tegumentar americana: apresentação clínica pseudolinfomatosa. v. 12, n. 4, p. 168–170, 2007. MARTINEZ, F. O.; GORDON, S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000prime reports, v. 6, n. March, p. 13, 2014. MAUËL, J.; RANSIJN, A; BUCHMÜLLER-ROUILLER, Y. Killing of Leishmania parasites in activated murine macrophages is based on an L-arginine-dependent process that produces nitrogen derivatives. Journal of leukocyte biology, v. 49, n. 1, p. 73–82, 1991. MEIRA, A. R. Splendore : facets of life of the Toxoplasma discoverer. Scientia, v. 20, p. 9– 12, 2010. MINODIER, P. et al. Leishmaniasis treatment. Archives of pediatrics, v. 17, n. 6, p. 838– 839, 2010. MOAN, J., PENG, Q. An outline of the hundred year history of PDT. Anticancer Research, v. 23, p. 3561–3600, 2003. MODOLELL, M. et al. Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis. PLoS Neglected Tropical Diseases, v. 3, n. 7, 2009. MONTENEGRO, D. Utilization of Pentamidine for Mucosal Leishmaniasis Treatment. Revista da Sociedade Brasileira de Medicina Tropical, v. 30, n. 6, p. 529–530, 1997. MOORE, J. V; WEST, C. M.; WHITEHURST, C. The biology of photodynamic therapy. Physics in medicine and biology, v. 42, n. 5, p. 913–935, 1997. MUNDER, M.; EICHMANN, K.; MODOLELL, M. Alternative metabolic states in murine macrophages reflected by the nitric oxide synthase/arginase balance: competitive regulation by CD4+ T cells correlates with Th1/Th2 phenotype. Journal of immunology (Baltimore, Md. : 1950), v. 160, n. 11, p. 5347–5354, 1998. MURBACK, N. D. N. et al. Leishmaniose tegumentar americana: Estudo clínico, epidemiológico e laboratorial realizado no Hospital Universitário de Campo Grande, Mato Grosso do Sul, Brasil. Anais Brasileiros de Dermatologia, v. 86, n. 1, p. 55–63, 2011. MURRAY, H. W. et al. Advances in leishmaniasis. Lancet, v. 366, n. 9496, p. 1561–1577, 2005. NOËL, W. et al. Alternatively activated macrophages during parasite infections. Trends in Parasitology, v. 20, n. 3, p. 126–133, 2004. NOVAIS, F. O. et al. Neutrophils and macrophages cooperate in host resistance against Leishmania braziliensis infection. Journal of immunology (Baltimore, Md. : 1950), v. 183, n. 12, p. 8088–8098, 2009. NOWIS, D. et al. Direct tumor damage mechanisms of photodynamic therapy. Acta Biochimica Polonica, v. 52, n. 2, p. 339–352, 2005. O’CONNOR, A. E.; GALLAGHER, W. M.; BYRNE, A. T. Porphyrin and nonporphyrin photosensitizers in oncology: Preclinical and clinical advances in photodynamic therapy. Photochemistry and Photobiology, v. 85, n. 5, p. 1053–1074, 2009. OTTERBEIN, L. E. et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nature medicine, v. 6, n. 4, p. 422–428, 2000. PANEK, H.; O’BRIAN, M. R. A whole genome view of prokaryotic haem biosynthesis. Microbiology, v. 148, n. 8, p. 2273–2282, 2002. PAULINO, T. P. et al. Use of visible light-based photodynamic therapy to bacterial photoinactivation. Biochemistry and Molecular Biology Education, v. 33, n. 1, p. 46–49, 2005. PELOI, L. S. et al. Photodynamic therapy for American cutaneous leishmaniasis: The efficacy of methylene blue in hamsters experimentally infected with Leishmania (Leishmania) amazonensis. Experimental Parasitology, v. 128, n. 4, p. 353–356, 2011. PIANTADOSI, C. A. et al. Heme oxygenase-1 couples activation of mitochondrial biogenesis to anti-inflammatory cytokine expression. Journal of Biological Chemistry, v. 286, n. 18, p. 16374–16385, 2011. PICCIRILLO, C. A. Regulatory T cells in health and disease. Cytokine, v. 43, n. 3, p. 395– 401, 2008. POOLE, R. K.; HUGHES, M. N. New functions for the ancient globin family: Bacterial responses to nitric oxide and nitrosative stress. Molecular Microbiology, v. 36, n. 4, p. 775– 783, 2000. PUSHPAN, S. K. et al. Porphyrins in photodynamic therapy - a search for ideal photosensitizers. Current medicinal chemistry. Anti-cancer agents, v. 2, n. 2, p. 187–207, 2002. RAFFERTY, S. et al. Giardia lamblia encodes a functional flavohemoglobin. Biochemical and Biophysical Research Communications, v. 399, n. 3, p. 347–351, 2010. RIBEIRO, J. N. et al. Avaliação da atividade fotodin??mica de porfirinas para uso em terapia fotodinâmica através da fotoxidação de triptofano. Ecletica Quimica, v. 32, n. 1, p. 7–14, 2007. RIITTER, U., FRISCHKNECHT, F., VANZANDBERGEN, G. Are neutrophils important host cells fo leishmania parisites? Trends in Parasitology, v. 25, n. 11, p. 505–510, 2009. ROBERTS, M. T. M. Current understandings on the immunology of leishmaniasis and recent developments in prevention and treatment. British Medical Bulletin, v. 75-76, n. 1, p. 115– 130, 2005. ROBERTSON, C. A.; EVANS, D. H.; ABRAHAMSE, H. Photodynamic therapy (PDT): A short review on cellular mechanisms and cancer research applications for PDT. Journal of Photochemistry and Photobiology B: Biology, v. 96, n. 1, p. 1–8, 2009. RYTER, S. W.; ALAM, J.; CHOI, A. M. K. Heme Oxygenase-1 / Carbon Monoxide : From Basic Science to Therapeutic Applications. Physiol Rev, v. 86, p. 583–650, 2006. SABAT, R. et al. Biology of interleukin-10. Cytokine and Growth Factor Reviews, v. 21, n. 5, p. 331–344, 2010. SACKS, D.; NOBEN-TRAUTH, N. The immunology of susceptibility and resistance to Leishmania major in mice. Nature reviews. Immunology, v. 2, n. 11, p. 845–858, 2002. SAH, J. F. et al. Genetic rescue of Leishmania deficiency in porphyrin biosynthesis creates mutants suitable for analysis of cellular events in uroporphyria and for photodynamic therapy. Journal of Biological Chemistry, v. 277, n. 17, p. 14902–14909, 2002. SAMPAIO, S. A. P., RIVITTI, E. A. Dermatologia. 3th. ed. São Paulo: Artes Médicas, p.1197-1225, 2007. SHARMAN, W.; ALLEN, C.; VAN LIER JE. Photodynamic therapeutics: basic principles and clinical applications. Drug discovery today, v. 4, n. 11, p. 507–517, 1999. SHIO, M. T.; OLIVIER, M. Editorial: Leishmania survival mechanisms: the role of host phosphatases. Journal of leukocyte biology, v. 88, n. 1, p. 1–3, 2010. SOHL, S. et al. Photodynamic treatment of cutaneous leishmaniasis. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG, v. 5, n. 2, p. 128–130, 2007. SOJKA, D. K.; HUANG, Y. H.; FOWELL, D. J. Mechanisms of regulatory T-cell suppression - A diverse arsenal for a moving target. Immunology, v. 124, n. 1, p. 13–22, 2008. SONG, D. et al. Phodynamic therapy using methylene blue to treat cutaneous leishmaniasis. Photomedicine and laser surgery, p. 711–715, 2011. SOTO, J. et al. Miltefosine for new world cutaneous leishmaniasis. Clinical infectious diseases, v. 38, n. 9, p. 1266–1272, 2004. SOUZA, W. D. et al. Doenças neglicenciadas, Rio de Janeiro: Acadêmia Brasileira de Ciências, p.1-58, 2010. STENGER, B. S. et al. Tissue Expression of Inducible Nitric Oxide Synthase Is Closely Associated with Resistance to Leishmania Major. Journal experimental medicine, v. 180, p.783-793, 1994. STERNBERG, E. D.; DOLPHIN, D.; BRÜCKNER, C. Porphyrin-based photosensitizers for use in photodynamic therapy. Tetrahedron, v. 54, n. 17, p. 4151–4202, 1998. STOCKER, R. et al. Bilirubin is an antioxidant of possible physiological importance. Science (New York, N.Y.), v. 235, n. 4792, p. 1043–1046, 1987. TOJAL DA SILVA, A. C. et al. Species diversity causing human cutaneous leishmaniasis in Rio Branco, state of Acre, Brazil. Tropical Medicine and International Health, v. 11, n. 9, p. 1388–1398, 2006. TOREZAN, L.; NIWA, A. B. M.; NETO, C. F. Terapia fotodinâmica em dermatologia: Princípios básicos e aplicações. Anais Brasileiros de Dermatologia, v. 84, n. 5, p. 445–459, 2009. TRIESSCHEIJN, M. et al. Photodynamic therapy in oncology. The oncologist, v. 11, n. 9, p. 1034–1044, 2006. TRINCHIERI, G.; GEROSA, F. Immunoregulation by interleukin-12. Journal of leukocyte biology, v. 59, n. 4, p. 505–511, 1996. VAN ZANDBERGEN, G. et al. Leishmania promastigotes release a granulocyte chemotactic factor and induce interleukin-8 release but inhibit gamma interferon-inducible protein 10 production by neutrophil granulocytes. Infection and Immunity, v. 70, n. 8, p. 4177–4184, 2002. VERRECK, F. A W. et al. Human IL-23-producing type 1 macrophages promote but IL-10- producing type 2 macrophages subvert immunity to (myco)bacteria. Proceedings of the National Academy of Sciences of the United States of America, v. 101, n. 13, p. 4560– 4565, 2004. VON STEBUT, E. et al. Interleukin 1alpha promotes Th1 differentiation and inhibits disease progression in Leishmania major-susceptible BALB/c mice. The Journal of experimental medicine, v. 198, n. 2, p. 191–199, 2003. VON TAPPEINER, H., JESIONEK, A. Therapeutische versuche mit fluoreszierenden stoffen. Munchiner Med Wochenschr, v. 50, n. 47, p. 2042–2044, 1903. WACHOWSKA, M. et al. Aminolevulinic acid (ala) as a prodrug in photodynamic therapy of cancer. Molecules, v. 16, n. 5, p. 4140–4164, 2011. WALTERS, L. L. Leishmania differenciation in natural and unnatural sand fly host. Journal of Eukariotic microbiology, v. 40, n. 2, p. 196–206, 1993. WANG, Z. E. et al. CD4+ effector cells default to the Th2 pathway in interferon gammadeficient mice infected with Leishmania major. The Journal of experimental medicine, v. 179, n. 4, p. 1367–1371, 1994. WORTMANN, G. et al. A randomized, double-blind study of the efficacy of a 10- or 20-day course of sodium stibogluconate for treatment of cutaneous leishmaniasis in United States military personnel. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, v. 35, n. 3, p. 261–267, 2002. ZHANG, Y. et al. Hypoxia reduces the expression of heme oxygenase-2 in various types of human cell lines: A possible strategy for the maintenance of intracellular heme level. FEBS Journal, v. 273, n. 14, p. 3136–3147, 2006. ZIZZO, G. et al. Efficient clearance of early apoptotic cells by human macrophages requires M2c polarization and MerTK induction. Journal of immunology, v. 189, n. 7, p. 3508–20, 2012.http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFTMinstname:Universidade Federal do Triangulo Mineiro (UFTM)instacron:UFTM2019-06-26T19:21:44Zoai:bdtd.uftm.edu.br:tede/266Biblioteca Digital de Teses e Dissertaçõeshttp://bdtd.uftm.edu.br/PUBhttp://bdtd.uftm.edu.br/oai/requestbdtd@uftm.edu.br||bdtd@uftm.edu.bropendoar:2019-06-26T19:21:44Biblioteca Digital de Teses e Dissertações da UFTM - Universidade Federal do Triangulo Mineiro (UFTM)false
dc.title.none.fl_str_mv Análise de macrófagos M1 e M2 em modelo experimental de leishmaniose cutânea submetido à terapia fotodinâmica associada ao ácido 5-aminolevulínico
Analysis of macrophage types M1 and M2 in an experimental model of cutaneous leishmaniasis treated with photodynamic therapy associated with 5-aminolevulinic acid
title Análise de macrófagos M1 e M2 em modelo experimental de leishmaniose cutânea submetido à terapia fotodinâmica associada ao ácido 5-aminolevulínico
spellingShingle Análise de macrófagos M1 e M2 em modelo experimental de leishmaniose cutânea submetido à terapia fotodinâmica associada ao ácido 5-aminolevulínico
SILVA, Mona Lisa Fabiana
Terapia Fotodinâmica
ALA-TFD
Leishmania braziliensis
ácido 5- aminolevulinico
Macrófagos
Photodynamic therapy
ALA-PDT
Leishmania braziliensis
5-aminolevulinic acid
Macrophages
Parasitologia
title_short Análise de macrófagos M1 e M2 em modelo experimental de leishmaniose cutânea submetido à terapia fotodinâmica associada ao ácido 5-aminolevulínico
title_full Análise de macrófagos M1 e M2 em modelo experimental de leishmaniose cutânea submetido à terapia fotodinâmica associada ao ácido 5-aminolevulínico
title_fullStr Análise de macrófagos M1 e M2 em modelo experimental de leishmaniose cutânea submetido à terapia fotodinâmica associada ao ácido 5-aminolevulínico
title_full_unstemmed Análise de macrófagos M1 e M2 em modelo experimental de leishmaniose cutânea submetido à terapia fotodinâmica associada ao ácido 5-aminolevulínico
title_sort Análise de macrófagos M1 e M2 em modelo experimental de leishmaniose cutânea submetido à terapia fotodinâmica associada ao ácido 5-aminolevulínico
author SILVA, Mona Lisa Fabiana
author_facet SILVA, Mona Lisa Fabiana
author_role author
dc.contributor.none.fl_str_mv RODRIGUES JUNIOR, Virmondes
45813493620
http://lattes.cnpq.br/8909243237236516
PAULINO, Tony de Paiva
92251048634
http://lattes.cnpq.br/3179978364259887
dc.contributor.author.fl_str_mv SILVA, Mona Lisa Fabiana
dc.subject.por.fl_str_mv Terapia Fotodinâmica
ALA-TFD
Leishmania braziliensis
ácido 5- aminolevulinico
Macrófagos
Photodynamic therapy
ALA-PDT
Leishmania braziliensis
5-aminolevulinic acid
Macrophages
Parasitologia
topic Terapia Fotodinâmica
ALA-TFD
Leishmania braziliensis
ácido 5- aminolevulinico
Macrófagos
Photodynamic therapy
ALA-PDT
Leishmania braziliensis
5-aminolevulinic acid
Macrophages
Parasitologia
description Introdução: A leishmaniose é uma doença infecciosa causada por parasitas do gênero Leishmania. Sua forma cutânea é causada pela L. major no velho mundo e pela Leishmania braziliensis nas Américas. Devido a sua localização, a Terapia Fotodinâmica pode representar uma abordagem terapêutica interessante. Os macrófagos são as células hospedeiras da Leishmania no homem e podem ser classificados como macrófagos M1 ou M2 dependendo do padrão de citocinas secretado. Neste estudo, avaliamos o perfil de macrófagos do tipo1 e tipo 2, a efetividade da Terapia Fotodinâmica (TFD) utilizando ao ácido aminolevulínico (ALA) no tratamento da leishmaniose cutânea (LC) e os níveis de Heme oxigenase 1 (HO-1) em modelo experimental de leishmaniose tratado com ALA-TFD. Métodos: Camundongos BALB/c machos com quatro semanas foram infectados nas patas com 1x106 formas amastigotas de Leishmania braziliensis, após 4 semanas os camundongos foram tratados com ALA, LUZ ou com ALA-TFD. Foi avaliada ex vivo a expressão dos marcadores mRNA interleucina (IL)-10 e Arginase-1 para identificação de macrófagos M2, TNF-α e iNOS para M1 e HO-1 no local da infecção. Resultados: O número de parasitas diminuiu significativamente nos grupos com TFD quando comparado aos demais. Os Níveis de iNOS foram maiores, não significativamente, no grupo TFD. Não houve diferença na expressão dos demais produtos testados. Conclusão: A morte do parasita não parece ser mediada pela modulação de macrófagos M1 ou M2 neste modelo experimental de leishmaniose tratado com ALA-PDT. A terapia reduz significativamente a carga parasitária in vivo sem a eliminação completa do parasita. O aumento de iNOS sugere a sua participação nos mecanismo microbicidas ativados por ALAPDT.
publishDate 2015
dc.date.none.fl_str_mv 2015-06-29
2016-07-14T17:25:41Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv SILVA, Mona Lisa Fabiana. Análise de macrófagos M1 e M2 em modelo experimental de leishmaniose cutânea submetido à terapia fotodinâmica associada ao ácido 5-aminolevulínico. 2015. 43f. Dissertação (Mestrado em Ciências Fisiológicas) - Curso de Pós-Graduação em Ciências Fisiológicas, Universidade Federal do Triângulo Mineiro, Uberaba, 2015.
http://bdtd.uftm.edu.br/handle/tede/266
identifier_str_mv SILVA, Mona Lisa Fabiana. Análise de macrófagos M1 e M2 em modelo experimental de leishmaniose cutânea submetido à terapia fotodinâmica associada ao ácido 5-aminolevulínico. 2015. 43f. Dissertação (Mestrado em Ciências Fisiológicas) - Curso de Pós-Graduação em Ciências Fisiológicas, Universidade Federal do Triângulo Mineiro, Uberaba, 2015.
url http://bdtd.uftm.edu.br/handle/tede/266
dc.language.iso.fl_str_mv por
language por
dc.relation.none.fl_str_mv ABEBE, T. et al. Local increase of arginase activity in lesions of patients with cutaneous leishmaniasis in ethiopia. PLoS Neglected Tropical Diseases, v. 6, n. 6, p. 1–10, 2012. ACKROYD, R. et al. The history of photodetection and photodynamic therapy. Photochemistry and photobiology, v. 74, n. 5, p. 656–669, 2001. AGOSTINIS, P. et al. Photodynamic Therapy of Cancer : An Update. American Cancer Society, v. 61, p. 250–281, 2011. AGOSTINIS, P. et al. Photodynamic Therapy of Cancer: an Update. v. 61, n. 4, p. 250–281, 2012. AKILOV, O. E. et al. Parasiticidal effect of ??-aminolevulinic acid-based photodynamic therapy for cutaneous leishmaniasis is indirect and mediated through the killing of the host cells. Experimental Dermatology, v. 16, n. 8, p. 651–660, 2007. ALVES, J. M. P. et al. Identification and phylogenetic analysis of heme synthesis genes in trypanosomatids and their bacterial endosymbionts. PLoS ONE, v. 6, n. 8, 2011. ASILIAN, A.; DAVAMI, M. Comparison between the efficacy of photodynamic therapy and topical paromomycin in the treatment of Old World cutaneous leishmaniasis: A placebocontrolled, randomized clinical trial. Clinical and Experimental Dermatology, v. 31, n. 5, p. 634–637, 2006. AULER, H., BANZER, G. Untersuchungen Uber die Rolle der Porphyrine bei geschwulstkranken Menschen und Tieren. Cancer Research Clinical Oncology, v. 53, n. 65, p. 65–68, 1942. AWASTHI, A.; KUMAR, M. R.; SAHA, B. Immune Response to Leishmania infecction. Indian J. Med. Res., v. 119, n. June, p. 238–258, 2004. BABIOR, B. M. Phagocytes and oxidative stress. American Journal of Medicine, v. 109, n. 1, p. 33–44, 2000. BABIOR, B. M.; KIPNES, R. S.; CUMVU, J. T. The production by leukocytes of superoxide, a potencial bactericidal agent. v. 52, n. March, p. 741–744, 1973. BARRAL, A et al. Transforming growth factor beta as a virulence mechanism for Leishmania braziliensis. Proceedings of the National Academy of Sciences of the United States of America, v. 90, n. 8, p. 3442–3446, 1993. BASANO, S. D. A.; CAMARGO, L. M. A. Leishmaniose tegumentar americana: histórico, epidemiologia e perspectivas de controle. Revista Brasileira de Epidemiologia, v. 7, n. 3, p. 328–337, 2004. BEGNAMI, M. D. F. S. et al. Análise imuno-histoquímica das sintases do óxido nítrico em adenocarcinomas gástricos. Jornal Brasileiro de Patologia e Medicina Laboratorial, v. 40, n. 5, p. 351–357, 2004. BELKAID, Y.; PICCIRILLO, C. A; MENDEZ, S. CD4+ CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature, v. 420, n. September, p. 633–637, 2002. BERMAN, J. D. Human leishmaniasis: clinical, diagnostic, and chemotherapeutic developments in the last 10 years. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, v. 24, n. 4, p. 684–703, 1997. BIEDERMANN, T.; RÖCKEN, M.; CARBALLIDO, J. M. TH1 and TH2 lymphocyte development and regulation of TH cell-mediated immune responses of the skin. The journal of investigative dermatology. Symposium proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research, v. 9, n. 1, p. 5– 14, 2004. BOGDAN, C.; RÖLLINGHOFF, M.; DIEFENBACH, A. The role of nitric oxide in innate immunity. Immunological reviews, v. 173, n. 1, p. 17–26, 2000a. BOGDAN, C.; RÖLLINGHOFF, M.; DIEFENBACH, A. Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity. Current Opinion in Immunology, v. 12, n. 1, p. 64–76, 2000b. BONNETT, R. Photosensitizers of the porphyrin and phthalocyanine series for photodynamic therapy. Chemical Society reviews, v. 24, n. 1, p. 19–33, 1995. BRASIL. Ministério da Saúde. Manual de Vigilância da Leishmaniose Tegumentar Americana / Ministério da Saúde, Secretaria de Vigilância em Saúde, Departamento de Vigilância Epidemiológica. – 2. ed. – Brasília : Editora do Ministério da Saúde, p.187, 2007. BRASIL. Ministério da Saúde. Manual de Vigilância da Leishmaniose Tegumentar Americana / Ministério da Saúde, Secretaria de Vigilância em Saúde, Departamento de Vigilância Epidemiológica. – 2. ed. – Brasília : Editora do Ministério da Saúde, p.180, 2010. BREUSING, N. et al. Light-induced cytotoxicity after aminolevulinic acid treatment is mediated by heme and not by iron. Journal of Photochemistry and Photobiology B: Biology, v. 99, n. 1, p. 36–43, 2010. BRITO, M. E. F. et al. Species diversity of Leishmania (Viannia) parasites circulating in an endemic area for cutaneous leishmaniasis located in the Atlantic rainforest region of northeastern Brazil. Tropical Medicine and International Health, v. 14, n. 10, p. 1278– 1286, 2009. C. FALCÃO, S. et al. The presence of Tregs does not preclude immunity to reinfection with Leishmania braziliensis. International Journal for Parasitology, v. 42, n. 8, p. 771–780, 2012. CAMPOS-NETO, A. What about Th1 / Th2 in cutaneous leishmaniasis vaccine discovery ? Brazilian Journal Of Medical And Biological Research, v. 38, p. 979–984, 2005. CASTANO, A.; MROZ, P.; HAMBLIN, M. Photodynamic therapy and anti-tumour immunity. Nature Reviews Cancer, v. 6, n. 7, p. 535–545, 2006. CEDERBAUM, S. D. et al. Arginases I and II: Do their functions overlap? Molecular Genetics and Metabolism, v. 81, n. SUPPL., p. 38–44, 2004. CORREA, M. A. D., LOPEZ, M. R. Alternative macrophage activation: the diversity of one cell involved in innate immunity in response to it’s environmental complexity. Immunology, v. 26, n. 2, p. 73–86, 2007. COSTA, D. L. et al. Tr-1-Like CD4+CD25-CD127-/lowFOXP3- Cells Are the Main Source of Interleukin 10 in Patients With Cutaneous Leishmaniasis Due to Leishmania braziliensis. Journal of Infectious Diseases, v. 211, n. 5, p. 708–718, 2014. COSTA, J. M. L. et al. Clinical Modalites, Diagnosis e Therapeutic Aproach of the Tegumentary Leishmaniasis in Brazil. Gazeta Medica da Bahia, v. 79, n. V, p. 70–83, 2009. COUPER, K. N.; BLOUNT, D. G.; RILEY, E. M. IL-10: the master regulator of immunity to infection. Journal of immunology, v. 180, n. 9, p. 5771–5777, 2008. CROFT, S. L.; SUNDAR, S.; FAIRLAMB, A. H. Drug Resistance in Leishmaniasis. Society, v. 19, n. 1, p. 111–126, 2006. CRUZ, E. DE M. Inibição da arginase de Leishmania por frações do extrato etanólico de Cecropia pachystachya. FUNDAÇÃO OSWALDO CRUZ CENTRO DE PESQUISAS GONÇALO MONIZ, 2011. DA SILVA, M. F. L. et al. Leishmania amazonensis arginase compartmentalization in the glycosome is important for parasite infectivity. PLoS ONE, v. 7, n. 3, 2012. DANIELL, M. D., HILL, J. S. A history of photodynamic therapy. Australian and New Zealand Journal of Surgery, v. 61, n. 5, p. 340–348, 1991. DESJARDINS, M.; DESCOTEAUX, A. Inhibition of phagolysosomal biogenesis by the Leishmania lipophosphoglycan. The Journal of experimental medicine, v. 185, n. 12, p. 2061–2068, 1997. DESJEUX, P. Leishmaniasis: Public Health Aspects and Control. Clinics in Dermatology, v. 14, n. 5, p. 417–423, 1996. DOMINGOS, P. L. B. et al. OX40+ T lymphocytes and IFN-γ are associated with American tegumentary leishmaniasis pathogenesis. Anais brasileiros de dermatologia, v. 87, n. 6, p. 851–5, 2012. DUPASQUIER, M. et al. The dermal microenvironment induces the expression of the alternative activation marker CD301/mMGL in mononuclear phagocytes, independent of IL- 4/IL-13 signaling. Journal of leukocyte biology, v. 80, n. 4, p. 838–849, 2006. DUSSE, L. M. S. A.; VIEIRA, L. M.; CARVALHO, M. G. Revisão sobre óxido nítrico; Nitric oxide revision. J. bras. patol. med. lab, v. 39, n. 4, p. 343–350, 2003. EL-ON, J.; BRADLEY, D. J.; FREEMAN, J. C. Leishmania donovani: action of excreted factor on hydrolytic enzyme activity of macrophages from mice with genetically different resistance to infection. Experimental parasitology, v. 49, n. 2, p. 167–174, 1980. ENGWERDA, C. R.; ATO, M.; KAYE, P. M. Macrophages, pathology and parasite persistence in experimental visceral leishmaniasis. Trends in Parasitology, v. 20, n. 11, p. 524–530, 2004. ENK, C. D. et al. [Cutaneous leishmaniasis]. Hautarzt, v. 54, n. 6, p. 506–512, 2003. FARAH, F. S.; SAMRA, S. A; NUWAYRI-SALTI, N. The role of the macrophage in cutaneous leishmaniasis. Immunology, v. 29, n. 4, p. 755–764, 1975. FERREIRA, A. et al. A central role for free heme in the pathogenesis of severe malaria: The missing link? Journal of Molecular Medicine, v. 86, n. 10, p. 1097–1111, 2008. FOOTE, C. S. Mechanisms of Photosensitized Oxidation. Sciences-New York, v. 162, n. 3857, p. 963–970, 1968. FORATTINI, O. P. Nota sobre o encontro de Leishmania em roedores silvestres de zona endêmica de leishmaniose no Estado de São Paulo, Brasil. Revista paulista de Medicina, v. 53, n. 2, p. 155, 1958. FRANK, J. et al. Inhibition of heme oxygenase-1 increases responsiveness of melanoma cells to ALA-based photodynamic therapy. International Journal of Oncology, v. 31, n. 6, p. 1539–1545, 2007. FRIES, D. S., FAIRLAMB, A. H. Antiprotozoal agents. 6th. ed. New York: [s.n.]. FURUSAWA, G. P.; BORGES, M. F. Colaboração Para O Conhecimento Do Histórico Da Leishmaniose Tegumentar Americana No Brasil: Possíveis Casos Entre Escravos Na Vila De Vassouras-Rj, Nos Anos 1820 a 1880. Revista de Patologia Tropical, v. 43, n. 1, p. 7–25, 2014. FURUYAMA, K.; KANEKO, K.; VARGAS, P. D. Heme as a magnificent molecule with multiple missions: heme determines its own fate and governs cellular homeostasis. The Tohoku journal of experimental medicine, v. 213, n. 1, p. 1–16, 2007. GARDLO, K. et al. Treatment of cutaneous leishmaniasis by photodynamic therapy. Journal of the American Academy of Dermatology, v. 48, n. 6, p. 893–896, 2003. GARDLO, K. et al. Photodynamische therapie bei kutaner leishmaniose: Eine viel versprechende neue therapiemodalit. Hautarzt, v. 55, n. 4, p. 381–383, 2004. GHAFFARIFAR, F. et al. Photodynamic therapy as a new treatment of cutaneous leishmaniasis. Eastern Mediterranean health journal = La revue de santé de la Méditerranée orientale = al-Majallah al-ṣiḥḥīyah li-sharq al-mutawassiṭ, v. 12, n. 6, p. 902–8, 2006. GOBERT, A. P. et al. L-arginine availability modulates local nitric oxide production and parasite killing in experimental trypanosomiasis. Infection and Immunity, v. 68, n. 8, p. 4653–4657, 2000. GONTIJO, B.; DE CARVALHO, M. D. L. R. Leishmaniose tegumentar Americana. Revista da Sociedade Brasileira de Medicina Tropical, v. 36, n. 1, p. 71–80, 2003. GONTIJO, C. M. F.; MELO, M. N. Leishmaniose visceral no Brasil: quadro atual, desafios e perspectivas. Revista Brasileira de Epidemiologia, v. 7, n. 3, p. 338–349, 2004. GORDON, S.; MARTINEZ, F. O. Alternative activation of macrophages: Mechanism and functions. Immunity, v. 32, n. 5, p. 593–604, 2010. GORMAN, A. et al. In vitro demonstration of the heavy-atom effect for photodynamic therapy. Journal of the American Chemical Society, v. 126, n. 34, p. 10619–10631, 2004. GREEN, S. J., MELTZER, M. S., HIBBS JR, J. B., NACY, C. A. Activated macrophages destroy intracelular Leishmania major amastigotes by L-arginine-dependent killing mechanism. The journal of immunology, v. 144, n. 1, p. 278–283, 1990. GREVELINK, S. A; LEMER, E. A. Leishmaniasis. Jounal of the american academy of dermatology, v. 34, n. 2, p. 257–272, 1996. GRODY, W. W. et al. Differential expression of the two human arginase genes in hyperargininemia. Enzymatic, pathologic, and molecular analysis. Journal of Clinical Investigation, v. 83, n. 2, p. 602–609, 1989. GURUVAYOORAPPAN, C. Tumor versus tumor-associated macrophages: how hot is the link? Integrative cancer therapies, v. 7, n. 2, p. 90–95, 2008. HANDMAN, E. Leishmaniasis : Current Status of Vaccine Development Leishmaniasis : Current Status of Vaccine Development. Clinical Microbiology Reviews, v. 14, n. 2, p. 229– 243, 2001. HANDMAN, E.; BULLEN, D. V. R. Interaction of Leishmania with the host macrophage. Trends in Parasitology, v. 18, n. 8, p. 332–334, 2002. HEINZEL, FP, SCHOENHAUT, DS, RERKO, R. M, ROSSER, L., GATELY, M. K. Recombinant Interleukin 12 Cures Mice Infected with Leishmania major. The Journal of experimental medicine, v. 177, n. 5, p. 1505–1509, 1993. HESSE, M. et al. Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of L-arginine metabolism. Journal of immunology, v. 167, n. 11, p. 6533–6544, 2001. HRYHORENKO, E. A et al. Antigen specific and nonspecific modulation of the immune response by aminolevulinic acid based photodynamic therapy. Immunopharmacology, v. 40, n. 3, p. 231–240, 1998. IBANEZ SIMPLICIO, F.; MAIONCHI, F.; HIOKA, N. Terapia fotodinâmica: Aspectos farmacológicos, aplicações e avanços recentes no desenvolvimento de medicamentos. Quimica Nova, v. 25, n. 5, p. 801–807, 2002. ISSA, M. C. A.; MANELA-AZULAY, M. Photodynamic therapy: a review of the literature and image documentation. Anais brasileiros de dermatologia, v. 85, n. 4, p. 501–511, 2010. JACOBINA, R. R.; GELMAN, E. A. Juliano Moreira and the Gazeta Medica da Bahia. Historia, ciencias, saude--Manguinhos, v. 15, n. 4, p. 1077–1097, 2008. JENKINSON, C. P.; GRODY, W. W.; CEDERBAUM, S. D. Comparative properties of arginases. Comparative Biochemistry and Physiology - B Biochemistry and Molecular Biology, v. 114, n. 1, p. 107–132, 1996. JORI, G. Tumour photosensitizers: Approaches to enhance the selectivity and efficiency of photodynamic therapy. Journal of Photochemistry and Photobiology B: Biology, v. 36, n. 2, p. 87–93, 1996. KAYE, P.; SCOTT, P. Leishmaniasis: complexity at the host-pathogen interface. Nature reviews. Microbiology, v. 9, n. 8, p. 604–615, 2011. KENNEDY, J. Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. Journal of Photochemistry and Photobiology B: Biology, v. 6, p. 143–148, 1990. KESSEL, D. et al. Modes of photodynamic vs. sonodynamic cytotoxicity. Journal of photochemistry and photobiology. B, Biology, v. 28, n. 3, p. 219–221, 1995. KHARKWAL, G. B. et al. Photodynamic Therapy for Infections: Clinical Applications. v. 43, n. 7, p. 755–767, 2012. KIM, C. H. et al. Synergistic effects of 5-aminolevulinic acid based photodynamic therapy and celecoxib via oxidative stress in human cholangiocarcinoma cells. International Journal of Nanomedicine, v. 8, p. 2173–2186, 2013. KOPF, M., BROMBACHER, F. KOHLER, G., KIENZLE, G.; WIDMANN, K., LEFRANG, K.; HUMBORG, C., LEDERMANN, B., SOLBACH, W. IL-4-deficient Balb/c Mice Resist Infection with Leishmania major. Immunological reviews, v. 184, n. 3, p. 1127–1136, 1996. KOŘENÝ, L.; LUKEŠ, J.; OBORNÍK, M. Evolution of the haem synthetic pathway in kinetoplastid flagellates: An essential pathway that is not essential after all? International Journal for Parasitology, v. 40, n. 2, p. 149–156, 2010. LAUNOIS, P., LOUIS, J. A., MILON, G. The fate and persistence of Leishmania major in mice of different genetic backgrounds: an example of exploitation of the immune system by intracellular parasites. Parasitology, v. 115, p. 25–32, 1997. LEE, T.-S.; TSAI, H.-L.; CHAU, L.-Y. Induction of heme oxygenase-1 expression in murine macrophages is essential for the anti-inflammatory effect of low dose 15-deoxy-Delta 12,14- prostaglandin J2. The Journal of biological chemistry, v. 278, n. 21, p. 19325–19330, 2003. LETTERIO, J. J.; ROBERTS, A B. Regulation of immune responses by TGF-beta. Annual review of immunology, v. 16, n. 1, p. 137–161, 1998. LIEW, F. Y. et al. Tumour necrosis factor (TNF alpha) in leishmaniasis. I. TNF alpha mediates host protection against cutaneous leishmaniasis. Immunology, v. 69, n. 4, p. 570– 573, 1990. LIEW, F. Y.; WEI, X. Q.; PROUDFOOT, L. Cytokines and nitric oxide as effector molecules against parasitic infections. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, v. 352, n. 1359, p. 1311–1315, 1997. LIMA, M. S. D. C. et al. Identificação de espécies de Leishmania isoladas de casos humanos em Mato Grosso do Sul por meio da reação em cadeia da polimerase. Revista da Sociedade Brasileira de Medicina Tropical, v. 42, n. 3, p. 303–308, 2009. LIU, D.; UZONNA, J. E. The early interaction of Leishmania with macrophages and dendritic cells and its influence on the host immune response. Frontiers in Cellular and Infection Microbiology, v. 2, n. June, p. 1–8, 2012. LU, J. et al. Discrete functions of M2a and M2c macrophage subsets determine their relative efficacy in treating chronic kidney disease. Kidney international, v. 84, n. 4, p. 745–55, 2013. LUZ, N. F. Papel da proteína heme oxigenase 1 na infecção de macrófagos por Leishmania chagasi. [s.l.] Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz, 2011. LUZ, N. F. et al. Heme oxygenase-1 promotes the persistence of Leishmania chagasi infection. Journal of immunology (Baltimore, Md. : 1950), v. 188, n. 9, p. 4460–7, 2012. MARCONDES, C. B. et al. A survey of visceral leishmaniasis in dogs from Santa Maria and neighbouring municipalities, State of Rio Grande do Sul. Revista da Sociedade Brasileira de Medicina Tropical, v. 36, n. 4, p. 499–501, 2003. MARQUES, S. A. Leishmaniose tegumentar americana: apresentação clínica pseudolinfomatosa. v. 12, n. 4, p. 168–170, 2007. MARTINEZ, F. O.; GORDON, S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000prime reports, v. 6, n. March, p. 13, 2014. MAUËL, J.; RANSIJN, A; BUCHMÜLLER-ROUILLER, Y. Killing of Leishmania parasites in activated murine macrophages is based on an L-arginine-dependent process that produces nitrogen derivatives. Journal of leukocyte biology, v. 49, n. 1, p. 73–82, 1991. MEIRA, A. R. Splendore : facets of life of the Toxoplasma discoverer. Scientia, v. 20, p. 9– 12, 2010. MINODIER, P. et al. Leishmaniasis treatment. Archives of pediatrics, v. 17, n. 6, p. 838– 839, 2010. MOAN, J., PENG, Q. An outline of the hundred year history of PDT. Anticancer Research, v. 23, p. 3561–3600, 2003. MODOLELL, M. et al. Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis. PLoS Neglected Tropical Diseases, v. 3, n. 7, 2009. MONTENEGRO, D. Utilization of Pentamidine for Mucosal Leishmaniasis Treatment. Revista da Sociedade Brasileira de Medicina Tropical, v. 30, n. 6, p. 529–530, 1997. MOORE, J. V; WEST, C. M.; WHITEHURST, C. The biology of photodynamic therapy. Physics in medicine and biology, v. 42, n. 5, p. 913–935, 1997. MUNDER, M.; EICHMANN, K.; MODOLELL, M. Alternative metabolic states in murine macrophages reflected by the nitric oxide synthase/arginase balance: competitive regulation by CD4+ T cells correlates with Th1/Th2 phenotype. Journal of immunology (Baltimore, Md. : 1950), v. 160, n. 11, p. 5347–5354, 1998. MURBACK, N. D. N. et al. Leishmaniose tegumentar americana: Estudo clínico, epidemiológico e laboratorial realizado no Hospital Universitário de Campo Grande, Mato Grosso do Sul, Brasil. Anais Brasileiros de Dermatologia, v. 86, n. 1, p. 55–63, 2011. MURRAY, H. W. et al. Advances in leishmaniasis. Lancet, v. 366, n. 9496, p. 1561–1577, 2005. NOËL, W. et al. Alternatively activated macrophages during parasite infections. Trends in Parasitology, v. 20, n. 3, p. 126–133, 2004. NOVAIS, F. O. et al. Neutrophils and macrophages cooperate in host resistance against Leishmania braziliensis infection. Journal of immunology (Baltimore, Md. : 1950), v. 183, n. 12, p. 8088–8098, 2009. NOWIS, D. et al. Direct tumor damage mechanisms of photodynamic therapy. Acta Biochimica Polonica, v. 52, n. 2, p. 339–352, 2005. O’CONNOR, A. E.; GALLAGHER, W. M.; BYRNE, A. T. Porphyrin and nonporphyrin photosensitizers in oncology: Preclinical and clinical advances in photodynamic therapy. Photochemistry and Photobiology, v. 85, n. 5, p. 1053–1074, 2009. OTTERBEIN, L. E. et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nature medicine, v. 6, n. 4, p. 422–428, 2000. PANEK, H.; O’BRIAN, M. R. A whole genome view of prokaryotic haem biosynthesis. Microbiology, v. 148, n. 8, p. 2273–2282, 2002. PAULINO, T. P. et al. Use of visible light-based photodynamic therapy to bacterial photoinactivation. Biochemistry and Molecular Biology Education, v. 33, n. 1, p. 46–49, 2005. PELOI, L. S. et al. Photodynamic therapy for American cutaneous leishmaniasis: The efficacy of methylene blue in hamsters experimentally infected with Leishmania (Leishmania) amazonensis. Experimental Parasitology, v. 128, n. 4, p. 353–356, 2011. PIANTADOSI, C. A. et al. Heme oxygenase-1 couples activation of mitochondrial biogenesis to anti-inflammatory cytokine expression. Journal of Biological Chemistry, v. 286, n. 18, p. 16374–16385, 2011. PICCIRILLO, C. A. Regulatory T cells in health and disease. Cytokine, v. 43, n. 3, p. 395– 401, 2008. POOLE, R. K.; HUGHES, M. N. New functions for the ancient globin family: Bacterial responses to nitric oxide and nitrosative stress. Molecular Microbiology, v. 36, n. 4, p. 775– 783, 2000. PUSHPAN, S. K. et al. Porphyrins in photodynamic therapy - a search for ideal photosensitizers. Current medicinal chemistry. Anti-cancer agents, v. 2, n. 2, p. 187–207, 2002. RAFFERTY, S. et al. Giardia lamblia encodes a functional flavohemoglobin. Biochemical and Biophysical Research Communications, v. 399, n. 3, p. 347–351, 2010. RIBEIRO, J. N. et al. Avaliação da atividade fotodin??mica de porfirinas para uso em terapia fotodinâmica através da fotoxidação de triptofano. Ecletica Quimica, v. 32, n. 1, p. 7–14, 2007. RIITTER, U., FRISCHKNECHT, F., VANZANDBERGEN, G. Are neutrophils important host cells fo leishmania parisites? Trends in Parasitology, v. 25, n. 11, p. 505–510, 2009. ROBERTS, M. T. M. Current understandings on the immunology of leishmaniasis and recent developments in prevention and treatment. British Medical Bulletin, v. 75-76, n. 1, p. 115– 130, 2005. ROBERTSON, C. A.; EVANS, D. H.; ABRAHAMSE, H. Photodynamic therapy (PDT): A short review on cellular mechanisms and cancer research applications for PDT. Journal of Photochemistry and Photobiology B: Biology, v. 96, n. 1, p. 1–8, 2009. RYTER, S. W.; ALAM, J.; CHOI, A. M. K. Heme Oxygenase-1 / Carbon Monoxide : From Basic Science to Therapeutic Applications. Physiol Rev, v. 86, p. 583–650, 2006. SABAT, R. et al. Biology of interleukin-10. Cytokine and Growth Factor Reviews, v. 21, n. 5, p. 331–344, 2010. SACKS, D.; NOBEN-TRAUTH, N. The immunology of susceptibility and resistance to Leishmania major in mice. Nature reviews. Immunology, v. 2, n. 11, p. 845–858, 2002. SAH, J. F. et al. Genetic rescue of Leishmania deficiency in porphyrin biosynthesis creates mutants suitable for analysis of cellular events in uroporphyria and for photodynamic therapy. Journal of Biological Chemistry, v. 277, n. 17, p. 14902–14909, 2002. SAMPAIO, S. A. P., RIVITTI, E. A. Dermatologia. 3th. ed. São Paulo: Artes Médicas, p.1197-1225, 2007. SHARMAN, W.; ALLEN, C.; VAN LIER JE. Photodynamic therapeutics: basic principles and clinical applications. Drug discovery today, v. 4, n. 11, p. 507–517, 1999. SHIO, M. T.; OLIVIER, M. Editorial: Leishmania survival mechanisms: the role of host phosphatases. Journal of leukocyte biology, v. 88, n. 1, p. 1–3, 2010. SOHL, S. et al. Photodynamic treatment of cutaneous leishmaniasis. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG, v. 5, n. 2, p. 128–130, 2007. SOJKA, D. K.; HUANG, Y. H.; FOWELL, D. J. Mechanisms of regulatory T-cell suppression - A diverse arsenal for a moving target. Immunology, v. 124, n. 1, p. 13–22, 2008. SONG, D. et al. Phodynamic therapy using methylene blue to treat cutaneous leishmaniasis. Photomedicine and laser surgery, p. 711–715, 2011. SOTO, J. et al. Miltefosine for new world cutaneous leishmaniasis. Clinical infectious diseases, v. 38, n. 9, p. 1266–1272, 2004. SOUZA, W. D. et al. Doenças neglicenciadas, Rio de Janeiro: Acadêmia Brasileira de Ciências, p.1-58, 2010. STENGER, B. S. et al. Tissue Expression of Inducible Nitric Oxide Synthase Is Closely Associated with Resistance to Leishmania Major. Journal experimental medicine, v. 180, p.783-793, 1994. STERNBERG, E. D.; DOLPHIN, D.; BRÜCKNER, C. Porphyrin-based photosensitizers for use in photodynamic therapy. Tetrahedron, v. 54, n. 17, p. 4151–4202, 1998. STOCKER, R. et al. Bilirubin is an antioxidant of possible physiological importance. Science (New York, N.Y.), v. 235, n. 4792, p. 1043–1046, 1987. TOJAL DA SILVA, A. C. et al. Species diversity causing human cutaneous leishmaniasis in Rio Branco, state of Acre, Brazil. Tropical Medicine and International Health, v. 11, n. 9, p. 1388–1398, 2006. TOREZAN, L.; NIWA, A. B. M.; NETO, C. F. Terapia fotodinâmica em dermatologia: Princípios básicos e aplicações. Anais Brasileiros de Dermatologia, v. 84, n. 5, p. 445–459, 2009. TRIESSCHEIJN, M. et al. Photodynamic therapy in oncology. The oncologist, v. 11, n. 9, p. 1034–1044, 2006. TRINCHIERI, G.; GEROSA, F. Immunoregulation by interleukin-12. Journal of leukocyte biology, v. 59, n. 4, p. 505–511, 1996. VAN ZANDBERGEN, G. et al. Leishmania promastigotes release a granulocyte chemotactic factor and induce interleukin-8 release but inhibit gamma interferon-inducible protein 10 production by neutrophil granulocytes. Infection and Immunity, v. 70, n. 8, p. 4177–4184, 2002. VERRECK, F. A W. et al. Human IL-23-producing type 1 macrophages promote but IL-10- producing type 2 macrophages subvert immunity to (myco)bacteria. Proceedings of the National Academy of Sciences of the United States of America, v. 101, n. 13, p. 4560– 4565, 2004. VON STEBUT, E. et al. Interleukin 1alpha promotes Th1 differentiation and inhibits disease progression in Leishmania major-susceptible BALB/c mice. The Journal of experimental medicine, v. 198, n. 2, p. 191–199, 2003. VON TAPPEINER, H., JESIONEK, A. Therapeutische versuche mit fluoreszierenden stoffen. Munchiner Med Wochenschr, v. 50, n. 47, p. 2042–2044, 1903. WACHOWSKA, M. et al. Aminolevulinic acid (ala) as a prodrug in photodynamic therapy of cancer. Molecules, v. 16, n. 5, p. 4140–4164, 2011. WALTERS, L. L. Leishmania differenciation in natural and unnatural sand fly host. Journal of Eukariotic microbiology, v. 40, n. 2, p. 196–206, 1993. WANG, Z. E. et al. CD4+ effector cells default to the Th2 pathway in interferon gammadeficient mice infected with Leishmania major. The Journal of experimental medicine, v. 179, n. 4, p. 1367–1371, 1994. WORTMANN, G. et al. A randomized, double-blind study of the efficacy of a 10- or 20-day course of sodium stibogluconate for treatment of cutaneous leishmaniasis in United States military personnel. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, v. 35, n. 3, p. 261–267, 2002. ZHANG, Y. et al. Hypoxia reduces the expression of heme oxygenase-2 in various types of human cell lines: A possible strategy for the maintenance of intracellular heme level. FEBS Journal, v. 273, n. 14, p. 3136–3147, 2006. ZIZZO, G. et al. Efficient clearance of early apoptotic cells by human macrophages requires M2c polarization and MerTK induction. Journal of immunology, v. 189, n. 7, p. 3508–20, 2012.
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Curso de Pós-Graduação em Ciências Fisiológicas - Parasitologia, Imunologia e Microbiologia
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collection Biblioteca Digital de Teses e Dissertações da UFTM
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da UFTM - Universidade Federal do Triangulo Mineiro (UFTM)
repository.mail.fl_str_mv bdtd@uftm.edu.br||bdtd@uftm.edu.br
_version_ 1797221126612451328