VEGF Promotes Malaria-Associated Acute Lung Injury in Mice
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/32494 http://dx.doi.org/10.1371/journal.ppat.1000916 |
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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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.Univ LisbonUniv Tecn LisboaInst Gulbenkian CienciasFac Med LisbonUniversidade de São Paulo (USP)Ctr Reg Oncol LisboaUniversidade Federal de São Paulo (UNIFESP)2016-01-24T13:59:37Z2016-01-24T13:59:37Z2010-05-01Plos Pathogens. San Francisco: Public Library Science, v. 6, n. 5, 10 p., 2010.1553-7366http://repositorio.unifesp.br/handle/11600/32494http://dx.doi.org/10.1371/journal.ppat.1000916WOS000278759900035.pdf10.1371/journal.ppat.1000916WOS:000278759900035The 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.Fundacao para a Ciencia e a Tecnologia (FCT)European Science FoundationGemi FundUniv 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, BrasilFundacao 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 2004Web of Science10engPublic Library SciencePlos PathogensVEGF Promotes Malaria-Associated Acute Lung Injury in Miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000278759900035.pdfapplication/pdf2876591${dspace.ui.url}/bitstream/11600/32494/1/WOS000278759900035.pdf934a7110695b37677df768369a4ade1eMD51open accessTEXTWOS000278759900035.pdf.txtWOS000278759900035.pdf.txtExtracted texttext/plain54090${dspace.ui.url}/bitstream/11600/32494/9/WOS000278759900035.pdf.txta65eda8232adf92554c9ae4a8ca660aeMD59open accessTHUMBNAILWOS000278759900035.pdf.jpgWOS000278759900035.pdf.jpgIM Thumbnailimage/jpeg7957${dspace.ui.url}/bitstream/11600/32494/11/WOS000278759900035.pdf.jpg7e9a0f2b203cee894c4a1e19bb660fd3MD511open access11600/324942023-06-05 19:24:52.112open accessoai:repositorio.unifesp.br:11600/32494Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-06-05T22:24:52Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.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.institution.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.issued.fl_str_mv |
2010-05-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T13:59:37Z |
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2016-01-24T13:59:37Z |
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dc.identifier.citation.fl_str_mv |
Plos Pathogens. San Francisco: Public Library Science, v. 6, n. 5, 10 p., 2010. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/32494 http://dx.doi.org/10.1371/journal.ppat.1000916 |
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1553-7366 |
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WOS000278759900035.pdf |
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10.1371/journal.ppat.1000916 |
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WOS:000278759900035 |
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Plos Pathogens. San Francisco: Public Library Science, v. 6, n. 5, 10 p., 2010. 1553-7366 WOS000278759900035.pdf 10.1371/journal.ppat.1000916 WOS:000278759900035 |
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