VEGF Promotes Malaria-Associated Acute Lung Injury in Mice

Detalhes bibliográficos
Autor(a) principal: Epiphanio, Sabrina [UNIFESP]
Data de Publicação: 2010
Outros Autores: Campos, Marta G., Pamplona, Ana, Carapau, Daniel, Pena, Ana C., Ataide, Ricardo, Monteiro, Carla A. A., Felix, Nuno, Costa-Silva, Artur, Marinho, Claudio R. F., Dias, Sergio, Mota, Maria M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://dx.doi.org/10.1371/journal.ppat.1000916
http://repositorio.unifesp.br/handle/11600/32494
Resumo: The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. the most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. in addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. the similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies.
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spelling VEGF Promotes Malaria-Associated Acute Lung Injury in MiceThe spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. the most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. in addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. the similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies.Univ Lisbon, Unidade Malaria, Inst Mol Med, P-1699 Lisbon, PortugalUniv Tecn Lisboa, Fac Vet Med Lisbon, P-1100 Lisbon, PortugalInst Gulbenkian Ciencias, Oeiras, PortugalFac Med Lisbon, Lisbon, PortugalUniv São Paulo, Dept Parasitol, São Paulo, BrazilCtr Reg Oncol Lisboa, Angiogenesis Lab, Ctr Invest Patobiol Mol, Inst Portugue Oncol Francisco Gentil, Lisbon, PortugalUniversidade Federal de São Paulo, ICAQF, Departamento de Ciências Biológicas, Diadema, BrasilWeb of ScienceFundacao para a Ciencia e a Tecnologia (FCT)European Science FoundationGemi FundFundacao para a Ciencia e a Tecnologia (FCT): POCTI/SAU-IMI/57946/2004Fundacao para a Ciencia e a Tecnologia (FCT): SFRH/BPD/31598/2006Fundacao para a Ciencia e a Tecnologia (FCT): SFRH/BD/10034/2002European Science Foundation: EURYI 2004Public Library ScienceUniv LisbonUniv Tecn LisboaInst Gulbenkian CienciasFac Med LisbonUniversidade de São Paulo (USP)Ctr Reg Oncol LisboaUniversidade Federal de São Paulo (UNIFESP)Epiphanio, Sabrina [UNIFESP]Campos, Marta G.Pamplona, AnaCarapau, DanielPena, Ana C.Ataide, RicardoMonteiro, Carla A. A.Felix, NunoCosta-Silva, ArturMarinho, Claudio R. F.Dias, SergioMota, Maria M.2016-01-24T13:59:37Z2016-01-24T13:59:37Z2010-05-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion10application/pdfhttp://dx.doi.org/10.1371/journal.ppat.1000916Plos Pathogens. San Francisco: Public Library Science, v. 6, n. 5, 10 p., 2010.10.1371/journal.ppat.1000916WOS000278759900035.pdf1553-7366http://repositorio.unifesp.br/handle/11600/32494WOS:000278759900035engPlos Pathogensinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-07T08:53:21Zoai:repositorio.unifesp.br/:11600/32494Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-07T08:53:21Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv VEGF Promotes Malaria-Associated Acute Lung Injury in Mice
title VEGF Promotes Malaria-Associated Acute Lung Injury in Mice
spellingShingle VEGF Promotes Malaria-Associated Acute Lung Injury in Mice
Epiphanio, Sabrina [UNIFESP]
title_short VEGF Promotes Malaria-Associated Acute Lung Injury in Mice
title_full VEGF Promotes Malaria-Associated Acute Lung Injury in Mice
title_fullStr VEGF Promotes Malaria-Associated Acute Lung Injury in Mice
title_full_unstemmed VEGF Promotes Malaria-Associated Acute Lung Injury in Mice
title_sort VEGF Promotes Malaria-Associated Acute Lung Injury in Mice
author Epiphanio, Sabrina [UNIFESP]
author_facet Epiphanio, Sabrina [UNIFESP]
Campos, Marta G.
Pamplona, Ana
Carapau, Daniel
Pena, Ana C.
Ataide, Ricardo
Monteiro, Carla A. A.
Felix, Nuno
Costa-Silva, Artur
Marinho, Claudio R. F.
Dias, Sergio
Mota, Maria M.
author_role author
author2 Campos, Marta G.
Pamplona, Ana
Carapau, Daniel
Pena, Ana C.
Ataide, Ricardo
Monteiro, Carla A. A.
Felix, Nuno
Costa-Silva, Artur
Marinho, Claudio R. F.
Dias, Sergio
Mota, Maria M.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Univ Lisbon
Univ Tecn Lisboa
Inst Gulbenkian Ciencias
Fac Med Lisbon
Universidade de São Paulo (USP)
Ctr Reg Oncol Lisboa
Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Epiphanio, Sabrina [UNIFESP]
Campos, Marta G.
Pamplona, Ana
Carapau, Daniel
Pena, Ana C.
Ataide, Ricardo
Monteiro, Carla A. A.
Felix, Nuno
Costa-Silva, Artur
Marinho, Claudio R. F.
Dias, Sergio
Mota, Maria M.
description The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. the most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. in addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. the similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies.
publishDate 2010
dc.date.none.fl_str_mv 2010-05-01
2016-01-24T13:59:37Z
2016-01-24T13:59:37Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1371/journal.ppat.1000916
Plos Pathogens. San Francisco: Public Library Science, v. 6, n. 5, 10 p., 2010.
10.1371/journal.ppat.1000916
WOS000278759900035.pdf
1553-7366
http://repositorio.unifesp.br/handle/11600/32494
WOS:000278759900035
url http://dx.doi.org/10.1371/journal.ppat.1000916
http://repositorio.unifesp.br/handle/11600/32494
identifier_str_mv Plos Pathogens. San Francisco: Public Library Science, v. 6, n. 5, 10 p., 2010.
10.1371/journal.ppat.1000916
WOS000278759900035.pdf
1553-7366
WOS:000278759900035
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Plos Pathogens
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 10
application/pdf
dc.publisher.none.fl_str_mv Public Library Science
publisher.none.fl_str_mv Public Library Science
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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