VEGF Promotes Malaria-Associated Acute Lung Injury in Mice

PLoS Pathogens

Claudio R. F. Marinho¹  Sérgio Dias¹  Ricardo Ataíde²  Marta G. Campos²  Daniel Carapau²  Maria M. Mota³  Carla A. A. Monteiro⁴  Artur Costa-Silva⁴  Sabrina Epiphanio⁴  Ana C. Pena⁴  Nuno Félix⁴  Ana Pamplona⁴ 

[1] Faculdade de Medicina Veterinária de Lisboa, Universidade Técnica de Lisboa, Portugal;Instituto Gulbenkian de Ciência, Oeiras, Portugal;Serviço de Anatomia Patológica, Hospital de Santa Maria e Faculdade de Medicina de Lisboa, Portugal;Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, Portugal

关键词: Plasmodium;    Respiratory infections;    Malaria;    Cerebral malaria;    Parasitic diseases;    Vascular permeability;    Edema;    Hemorrhage;   

DOI  :  10.1371/journal.ppat.1000916

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY