{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gillrie MR"],"funding":["NIAID NIH HHS"],"pagination":["3426-35"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2200906"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["110(9)"],"pubmed_abstract":["Pulmonary 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 and the cytosolic and nuclear 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."],"journal":["Blood"],"pubmed_title":["Src-family kinase dependent disruption of endothelial barrier function by Plasmodium falciparum merozoite proteins."],"pmcid":["PMC2200906"],"funding_grant_id":["AI 41139","R01 AI041139"],"pubmed_authors":["Gowda DC","Ho M","Gillrie MR","Looareesuwan S","Lee K","Buret AG","Krishnegowda G","Robbins SM"],"additional_accession":[]},"is_claimable":false,"name":"Src-family kinase dependent disruption of endothelial barrier function by Plasmodium falciparum merozoite proteins.","description":"Pulmonary 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 and the cytosolic and nuclear 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.","dates":{"release":"2007-01-01T00:00:00Z","publication":"2007 Nov","modification":"2025-04-22T12:54:42.981Z","creation":"2019-03-27T02:43:47Z"},"accession":"S-EPMC2200906","cross_references":{"pubmed":["17693580"],"doi":["10.1182/blood-2007-04-084582"]}}