VEGF Promotes Malaria-Associated Acute Lung Injury in Mice

VEGF Promotes Malaria-Associated Acute Lung Injury in Mice

Autor Epiphanio, Sabrina Autor UNIFESP Google Scholar
Campos, Marta G. Google Scholar
Pamplona, Ana Google Scholar
Carapau, Daniel Google Scholar
Pena, Ana C. Google Scholar
Ataide, Ricardo Google Scholar
Monteiro, Carla A. A. Google Scholar
Felix, Nuno Google Scholar
Costa-Silva, Artur Google Scholar
Marinho, Claudio R. F. Google Scholar
Dias, Sergio Google Scholar
Mota, Maria M. Google Scholar
Instituição 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)
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.
Idioma Inglês
Financiador Fundacao para a Ciencia e a Tecnologia (FCT)
European Science Foundation
Gemi Fund
Número do financiamento Fundacao para a Ciencia e a Tecnologia (FCT): POCTI/SAU-IMI/57946/2004
Fundacao para a Ciencia e a Tecnologia (FCT): SFRH/BPD/31598/2006
Fundacao para a Ciencia e a Tecnologia (FCT): SFRH/BD/10034/2002
European Science Foundation: EURYI 2004
Data 2010-05-01
Publicado em Plos Pathogens. San Francisco: Public Library Science, v. 6, n. 5, 10 p., 2010.
ISSN 1553-7366 (Sherpa/Romeo, fator de impacto)
Editor Public Library Science
Extensão 10
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000278759900035

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