Mark R. GillrieGowdahalli KrishnegowdaKristine LeeAndre G. BuretStephen M. RobbinsS. LooareesuwanD. Channe GowdaMay HoUniversity of CalgaryPenn State College of MedicineMahidol UniversityDepartment of Microbiology and Infectious Diseases2018-08-242018-08-242007-11-01Blood. Vol.110, No.9 (2007), 3426-343500064971000649712-s2.0-36148932964https://repository.li.mahidol.ac.th/handle/20.500.14594/24094Pulmonary complication in severe Plasmodium falciparum malaria is manifested as a prolonged impairment of gas transfer or the more severe acute respiratory distress syndrome (ARDS). In either clinical presentation, vascular permeability is a major component of the pathologic process. In this report, we examined the effect of clinical P falciparum isolates on barrier function of primary dermal and lung microvascular endothelium in vitro. We showed that parasite sonicates but not intact infected erythrocytes disrupted endothelial barrier function in a Src-family kinase-dependent manner. The abnormalities were manifested both as discontinuous immunofluorescence staining of the junctional proteins ZO-1, claudin 5, and VE-cadherin and the formation of interendothelial gaps in monolayers. These changes were associated with a loss in total protein content of claudin 5 and redistribution of ZO-1 from the cytoskeleton to the membrane andthe cytosolicandnuclear fractions. There was minimal evidence of a proinflammatory response or direct cellular cytotoxicity or cell death. The active component in sonicates appeared to be a merozoite-associated protein. Increased permeability was also induced by P falciparum glycophosphatidylinositols (GPIs) and food vacuoles. These results demonstrate that parasite components can alter endothelial barrier function and thus contribute to the pathogenesis of severe falciparum malaria. © 2007 by The American Society of Hematology.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyImmunology and MicrobiologyMedicineArticleSCOPUS10.1182/blood-2007-04-084582