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Please use this identifier to cite or link to this item: http://hdl.handle.net/10451/7050

Título: VEGF promotes malaria-associated acute lung injury in mice
Autor: Epiphanio, Sabrina
Campos, Marta G.
Pamplona, Ana
Carapau, Daniel
Pena, Ana C.
Ataíde, Ricardo
Monteiro, Carla A. A.
Félix, Nuno
Costa-Silva, Artur
Marinho, Claudio R. F.
Dias, Sérgio
Mota, Maria M.
Palavras-chave: Malaria
Acute lung injury
Spectrum analysis
Mice
Issue Date: 2010
Editora: Public Library of Science
Citação: PLoS Pathog 6(5):e1000916
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.
Descrição: © 2010 Epiphanio et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Arbitragem científica: yes
URI: http://dx.doi.org/10.1371/journal.ppat.1000916
http://hdl.handle.net/10451/7050
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000916
ISSN: 1553-7366
Appears in Collections:IMM - Artigos em Revistas Internacionais

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