Pathogenic CD8+ T Cells Cause Increased Levels of VEGF-A in Experimental Malaria-Associated Acute Respiratory Distress Syndrome, but Therapeutic VEGFR Inhibition Is Not Effective

摘要: Malaria is a severe disease and kills over 400,000 people each year. Malarial complications are the main cause of death include cerebral malaria malaria-associated acute respiratory distress syndrome (MA-ARDS). Despite antimalarial treatment, lethality rates MA-ARDS still between 20 80%. Patients develop pulmonary edema with hemorrhages leukocyte extravasation in lungs. The vascular endothelial growth factor-A (VEGF-A) placental factor (PlGF) permeability factors may be involved disruption alveolar-capillary membrane, leading to alveolar edema. We demonstrated increased VEGF-A PlGF levels lungs mice experimental MA-ARDS. Depletion pathogenic CD8+ T cells blocked abolished increase PlGF. However, neutralization VEGF receptor-2 (VEGFR-2) monoclonal antibody clone DC101 did not decrease pathology. broader spectrum receptor tyrosine kinase inhibitor sunitinib even lung These data suggest that but rather consequence pathology therapeutic inhibition receptors effective contra-indicated.