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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3426-3435. Prepublished online as a Blood First Edition Paper on August 10, 2007; DOI 10.1182/blood-2007-04-084582. This Article Full Text Full Text (PDF) Supplemental Methods, Table, and Figures All Versions of this Article: blood-2007-04-084582v1 110/9/3426    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gillrie, M. R. Articles by Ho, M. Search for Related Content PubMed PubMed Citation Articles by Gillrie, M. R. Articles by Ho, M. Related Collections Red Cells Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Src-family kinase–dependent disruption of endothelial barrier function by Plasmodium falciparum merozoite proteins Mark R. Gillrie1, Gowdahalli Krishnegowda2, Kristine Lee1, Andre G. Buret3, Stephen M. Robbins4, S. Looareesuwan5, D. Channe Gowda2, and May Ho1 1 Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, AB; 2 Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey; 3 Department of Biological Sciences, University of Calgary, Calgary, AB; 4 Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB; and 5 Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Larson, S. Schomberg, W. Schroeder, and T. C. Carpenter Endothelial EphA receptor stimulation increases lung vascular permeability Am J Physiol Lung Cell Mol Physiol, September 1, 2008; 295(3): L431 - L439. [Abstract] [Full Text] [PDF]

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