Avaliação do sistema purinérgico na pitiose experimental em coelhos tratados com imunoterápico
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/3834 |
Resumo: | Pythiosis is a disease caused by the oomycete Pythium insidiosum that affects horses, cattle, sheep, cats and humans, and occurs in tropical, subtropical and temperate regions. In horses the lesions are characterized by ulcerative eosinophilic granulomas. Most drugs are ineffective against this pathogen and immunotherapy has shown promise in the regression of the disease, even without the complete elucidation of the immune mechanisms involved. The purinergic system via adenine nucleotides (ATP and ADP) and its derivated nucleoside (adenosine), plays an important role in modulating the immune and inflammatory responses. Once released by cells, nucleotides interact with specific receptors and their extracellular concentrations are controlled by a group of ecto-enzymes, among which are ENTPDase (ecto-nucleoside triphosphate diphosphohydrolase) and ADA (adenosine deaminase). Taking into account the importance of immunotherapy in the treatment of pythiosis and a possible involvement of purinergic signaling in the immune response, the activities of E-NTPDase and E-ADA were evaluated in lymphocytes of rabbits with experimental pythiosis. For disease induction, zoospores were inoculated, subcutaneously, in the lateral region of the torax of each rabbit. These animals were evaluated weekly and the nodular area (cm2) developed was determined after 28 days of inoculation. Animals with experimental pythiosis, confirmed by enzyme immunoassay and the development of characteristic lesions, were treated with immunotherapy, whereas the ratio between the enzymatic activity in lymphopcytes and the consequent triggered immune response was investigated. Animals that did not develop lesions and those from the control group showed the same pattern of ectoenzymatic activity. E-NTPDase activity in lymphocytes of rabbits with experimental pythiosis was significantly higher (p<0,001) in relation to ATP hydrolysis (about 100%) and may be related to decreased (p<0,05) serum ATP (54,04%), when compared to the control group. After immunotherapeutic treatment, the activity of E-NTPDase showed similar values to those observed on the day of inoculation. Moreover, rabbits with experimental pythiosis showed a significant decrease (p<0,01) in the activity of E-ADA (82,36%), and this would lead to a significant increase in the extracellular concentration of adenosine (2,51 times), in relation to the control group (p<0,01). After immunotherapy, this group of animals showed a significant increase in the activity of E-ADA (78,62%) (p<0,01). Through this study, it can be observed that an increased activity of E-ADA, during pythiosis, leads to extracellular regulation of ATP and adenosine concentration. As a result, low levels of extracellular ATP could activate P2Y receptors, while high levels of extracellular adenosine may activate A2A and/or A2B receptors, triggering a TH2 response, responsible for the tissue damage generated by infection. After immunotherapy, it can be observed an inversion in the behaviour of the enzymatic activities, stimulating a TH1 response in the host. The switch from a TH2 response, responsible for the injuries that occur on pythiosis, to a TH1 response, is the most accepted hypothesis to explain the healing properties of immunotherapy. Thus, it is suggested the involvement of purinergic system in the pattern of immune response that occurs during pythiosis and after immunotherapy. |
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Avaliação do sistema purinérgico na pitiose experimental em coelhos tratados com imunoterápicoEvaluation of the purinergic system in rabbits with experimental pythiosis treated by immunotherapyPythium insidiosumPitioseATPAdenosinaSistema purinérgicoLTH1Resposta imunológicaImunoterapiaPythium insidiosumPythiosisATPAdenosinePurinergic systemLTH1Immune responseImmunotherapyCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAPythiosis is a disease caused by the oomycete Pythium insidiosum that affects horses, cattle, sheep, cats and humans, and occurs in tropical, subtropical and temperate regions. In horses the lesions are characterized by ulcerative eosinophilic granulomas. Most drugs are ineffective against this pathogen and immunotherapy has shown promise in the regression of the disease, even without the complete elucidation of the immune mechanisms involved. The purinergic system via adenine nucleotides (ATP and ADP) and its derivated nucleoside (adenosine), plays an important role in modulating the immune and inflammatory responses. Once released by cells, nucleotides interact with specific receptors and their extracellular concentrations are controlled by a group of ecto-enzymes, among which are ENTPDase (ecto-nucleoside triphosphate diphosphohydrolase) and ADA (adenosine deaminase). Taking into account the importance of immunotherapy in the treatment of pythiosis and a possible involvement of purinergic signaling in the immune response, the activities of E-NTPDase and E-ADA were evaluated in lymphocytes of rabbits with experimental pythiosis. For disease induction, zoospores were inoculated, subcutaneously, in the lateral region of the torax of each rabbit. These animals were evaluated weekly and the nodular area (cm2) developed was determined after 28 days of inoculation. Animals with experimental pythiosis, confirmed by enzyme immunoassay and the development of characteristic lesions, were treated with immunotherapy, whereas the ratio between the enzymatic activity in lymphopcytes and the consequent triggered immune response was investigated. Animals that did not develop lesions and those from the control group showed the same pattern of ectoenzymatic activity. E-NTPDase activity in lymphocytes of rabbits with experimental pythiosis was significantly higher (p<0,001) in relation to ATP hydrolysis (about 100%) and may be related to decreased (p<0,05) serum ATP (54,04%), when compared to the control group. After immunotherapeutic treatment, the activity of E-NTPDase showed similar values to those observed on the day of inoculation. Moreover, rabbits with experimental pythiosis showed a significant decrease (p<0,01) in the activity of E-ADA (82,36%), and this would lead to a significant increase in the extracellular concentration of adenosine (2,51 times), in relation to the control group (p<0,01). After immunotherapy, this group of animals showed a significant increase in the activity of E-ADA (78,62%) (p<0,01). Through this study, it can be observed that an increased activity of E-ADA, during pythiosis, leads to extracellular regulation of ATP and adenosine concentration. As a result, low levels of extracellular ATP could activate P2Y receptors, while high levels of extracellular adenosine may activate A2A and/or A2B receptors, triggering a TH2 response, responsible for the tissue damage generated by infection. After immunotherapy, it can be observed an inversion in the behaviour of the enzymatic activities, stimulating a TH1 response in the host. The switch from a TH2 response, responsible for the injuries that occur on pythiosis, to a TH1 response, is the most accepted hypothesis to explain the healing properties of immunotherapy. Thus, it is suggested the involvement of purinergic system in the pattern of immune response that occurs during pythiosis and after immunotherapy.A pitiose é uma doença causada pelo oomiceto Pythium insidiosum que acomete equinos, bovinos, ovinos, felinos e seres humanos, e ocorre em regiões tropicais, subtropicais e temperadas. Em equinos as lesões são caracterizadas por granulomas eosinofílicos ulcerados. A maioria das drogas antifúngicas é ineficaz contra este patógeno e a imunoterapia tem se mostrado promissora na regressão da doença, mesmo sem a elucidação completa dos mecanismos imunes envolvidos. O sistema purinérgico, através dos nucleotídeos de adenina (ATP e ADP) e seu derivado nucleosídeo (adenosina), desempenha um importante papel na modulação da resposta imune e inflamatória. Uma vez liberados pelas células, os nucleotídeos interagem com receptores específicos e suas concentrações extracelulares são controladas por um grupo de ecto-enzimas, entre as quais estão a E-NTPDase (Ecto-Nucleosídeo Trifosfato Difosfoidrolase) e ADA (adenosina desaminase). Levando-se em conta a importância da imunoterapia no tratamento da pitiose e uma possível participação da sinalização purinérgica na resposta imune, foram avaliadas as atividades das ecto-enzimas NTPDase e ADA em linfócitos de coelhos com pitiose experimental. Para a indução da doença, zoósporos foram inoculados por via subcutânea, na região lateral do tórax, de cada coelho. Os coelhos inoculados foram avaliados semanalmente e a área nodular (cm2) desenvolvida foi determinada após 28 dias da inoculação. Os animais com pitiose experimental, confirmada por teste imunoenzimático e pelo desenvolvimento de lesão característica, foram tratados com imunoterápico, sendo que a relação entre as atividades enzimáticas nos linfócitos e o tipo de resposta imune foi investigada. Os animais que não desenvolveram lesão e os animais do grupo controle mostraram o mesmo padrão de atividade das ectoenzimas. A atividade da E-NTPDase nos linfócitos dos coelhos com pitiose experimental mostrou-se significativamente maior (p<0,001) em relação à hidrólise de ATP (em cerca de 100%), podendo estar relacionada à diminuição (p<0,05) da concentração sérica de ATP (54,04%), quando comparado ao grupo controle. Após o tratamento com o imunoterápico, a atividade da E-NTPDase apresentou valores semelhantes aqueles observados no dia da inoculação. Por outro lado, os coelhos com pitiose experimental apresentaram uma diminuição significativa (p<0,01) na atividade da E-ADA (82,36%), o que levaria a um importante aumento na concentração extracelular de adenosina (2,51 vezes) em relação ao grupo controle (p<0,01). Após a imunoterapia, este grupo de animais apresentou um aumento significativo na atividade da E-ADA (78,62%) (p<0,01). Através deste estudo, podese observar que a atividade aumentada da E-NTPDase e a atividade diminuída da E-ADA, durante a pitiose, levam à regulação da concentração do ATP e da adenosina no meio extracelular. Em conseqüência, baixos níveis extracelulares de ATP poderiam ativar receptores P2Y, enquanto, altos níveis de adenosina poderiam ativar receptores A2A e/ou A2B desencadeando uma resposta TH2, responsável pelos danos teciduais gerados na infecção. Com a imunoterapia, pode-se observar uma inversão no comportamento das atividades enzimáticas, estimulando uma resposta TH1 no hospedeiro. A mudança de uma resposta TH2, responsável pelas lesões que ocorrem na pitiose, para um padrão de resposta TH1, é hipótese mais aceita para explicar as propriedades curativas da imunoterapia. Dessa forma, sugere-se a participação do sistema purinérgico no padrão de resposta imune que ocorre durante a pitiose e após a imunoterapia.Universidade Federal de Santa MariaBRFarmacologiaUFSMPrograma de Pós-Graduação em FarmacologiaSanturio, Janio Moraishttp://lattes.cnpq.br/6316012260769979Moreira, Cleci Menezeshttp://lattes.cnpq.br/5805841991374556Ferreiro, Laertehttp://lattes.cnpq.br/9848497567060083Alves, Sydney Hartzhttp://lattes.cnpq.br/0330782478769631Loreto, Érico Silva dehttp://lattes.cnpq.br/5475233864057995Bach, Barbara Charlotte2013-08-202013-08-202012-12-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfapplication/pdfBACH, Barbara Charlotte. Evaluation of the purinergic system in rabbits with experimental pythiosis treated by immunotherapy. 2012. 80 f. Tese (Doutorado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2012.http://repositorio.ufsm.br/handle/1/3834porinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2023-05-16T19:58:15Zoai:repositorio.ufsm.br:1/3834Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2023-05-16T19:58:15Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Avaliação do sistema purinérgico na pitiose experimental em coelhos tratados com imunoterápico Evaluation of the purinergic system in rabbits with experimental pythiosis treated by immunotherapy |
title |
Avaliação do sistema purinérgico na pitiose experimental em coelhos tratados com imunoterápico |
spellingShingle |
Avaliação do sistema purinérgico na pitiose experimental em coelhos tratados com imunoterápico Bach, Barbara Charlotte Pythium insidiosum Pitiose ATP Adenosina Sistema purinérgico LTH1 Resposta imunológica Imunoterapia Pythium insidiosum Pythiosis ATP Adenosine Purinergic system LTH1 Immune response Immunotherapy CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Avaliação do sistema purinérgico na pitiose experimental em coelhos tratados com imunoterápico |
title_full |
Avaliação do sistema purinérgico na pitiose experimental em coelhos tratados com imunoterápico |
title_fullStr |
Avaliação do sistema purinérgico na pitiose experimental em coelhos tratados com imunoterápico |
title_full_unstemmed |
Avaliação do sistema purinérgico na pitiose experimental em coelhos tratados com imunoterápico |
title_sort |
Avaliação do sistema purinérgico na pitiose experimental em coelhos tratados com imunoterápico |
author |
Bach, Barbara Charlotte |
author_facet |
Bach, Barbara Charlotte |
author_role |
author |
dc.contributor.none.fl_str_mv |
Santurio, Janio Morais http://lattes.cnpq.br/6316012260769979 Moreira, Cleci Menezes http://lattes.cnpq.br/5805841991374556 Ferreiro, Laerte http://lattes.cnpq.br/9848497567060083 Alves, Sydney Hartz http://lattes.cnpq.br/0330782478769631 Loreto, Érico Silva de http://lattes.cnpq.br/5475233864057995 |
dc.contributor.author.fl_str_mv |
Bach, Barbara Charlotte |
dc.subject.por.fl_str_mv |
Pythium insidiosum Pitiose ATP Adenosina Sistema purinérgico LTH1 Resposta imunológica Imunoterapia Pythium insidiosum Pythiosis ATP Adenosine Purinergic system LTH1 Immune response Immunotherapy CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
topic |
Pythium insidiosum Pitiose ATP Adenosina Sistema purinérgico LTH1 Resposta imunológica Imunoterapia Pythium insidiosum Pythiosis ATP Adenosine Purinergic system LTH1 Immune response Immunotherapy CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Pythiosis is a disease caused by the oomycete Pythium insidiosum that affects horses, cattle, sheep, cats and humans, and occurs in tropical, subtropical and temperate regions. In horses the lesions are characterized by ulcerative eosinophilic granulomas. Most drugs are ineffective against this pathogen and immunotherapy has shown promise in the regression of the disease, even without the complete elucidation of the immune mechanisms involved. The purinergic system via adenine nucleotides (ATP and ADP) and its derivated nucleoside (adenosine), plays an important role in modulating the immune and inflammatory responses. Once released by cells, nucleotides interact with specific receptors and their extracellular concentrations are controlled by a group of ecto-enzymes, among which are ENTPDase (ecto-nucleoside triphosphate diphosphohydrolase) and ADA (adenosine deaminase). Taking into account the importance of immunotherapy in the treatment of pythiosis and a possible involvement of purinergic signaling in the immune response, the activities of E-NTPDase and E-ADA were evaluated in lymphocytes of rabbits with experimental pythiosis. For disease induction, zoospores were inoculated, subcutaneously, in the lateral region of the torax of each rabbit. These animals were evaluated weekly and the nodular area (cm2) developed was determined after 28 days of inoculation. Animals with experimental pythiosis, confirmed by enzyme immunoassay and the development of characteristic lesions, were treated with immunotherapy, whereas the ratio between the enzymatic activity in lymphopcytes and the consequent triggered immune response was investigated. Animals that did not develop lesions and those from the control group showed the same pattern of ectoenzymatic activity. E-NTPDase activity in lymphocytes of rabbits with experimental pythiosis was significantly higher (p<0,001) in relation to ATP hydrolysis (about 100%) and may be related to decreased (p<0,05) serum ATP (54,04%), when compared to the control group. After immunotherapeutic treatment, the activity of E-NTPDase showed similar values to those observed on the day of inoculation. Moreover, rabbits with experimental pythiosis showed a significant decrease (p<0,01) in the activity of E-ADA (82,36%), and this would lead to a significant increase in the extracellular concentration of adenosine (2,51 times), in relation to the control group (p<0,01). After immunotherapy, this group of animals showed a significant increase in the activity of E-ADA (78,62%) (p<0,01). Through this study, it can be observed that an increased activity of E-ADA, during pythiosis, leads to extracellular regulation of ATP and adenosine concentration. As a result, low levels of extracellular ATP could activate P2Y receptors, while high levels of extracellular adenosine may activate A2A and/or A2B receptors, triggering a TH2 response, responsible for the tissue damage generated by infection. After immunotherapy, it can be observed an inversion in the behaviour of the enzymatic activities, stimulating a TH1 response in the host. The switch from a TH2 response, responsible for the injuries that occur on pythiosis, to a TH1 response, is the most accepted hypothesis to explain the healing properties of immunotherapy. Thus, it is suggested the involvement of purinergic system in the pattern of immune response that occurs during pythiosis and after immunotherapy. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-12-19 2013-08-20 2013-08-20 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
BACH, Barbara Charlotte. Evaluation of the purinergic system in rabbits with experimental pythiosis treated by immunotherapy. 2012. 80 f. Tese (Doutorado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2012. http://repositorio.ufsm.br/handle/1/3834 |
identifier_str_mv |
BACH, Barbara Charlotte. Evaluation of the purinergic system in rabbits with experimental pythiosis treated by immunotherapy. 2012. 80 f. Tese (Doutorado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
url |
http://repositorio.ufsm.br/handle/1/3834 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Farmacologia UFSM Programa de Pós-Graduação em Farmacologia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Farmacologia UFSM Programa de Pós-Graduação em Farmacologia |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1805922075718713344 |