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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 12, 2007 Accepted August 8, 2007 Src family kinase-dependent disruption of endothelial barrier function by Plasmodium falciparum merozoite proteins Mark R. Gillrie, Gowdahalli Krishnegowda, Kristine Lee, Andre G. Buret, Stephen M. Robbins, S. Looareesuwan, D. Channe Gowda, and May Ho* Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA, United States Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada Faculty of Tropical Medicine, Mahdiol University, Bangkok, Thailand * Corresponding author; email: mho{at}ucalgary.ca. Pulmonary complication in severe P. 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 pathological 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 re-distribution of ZO-1 from the cytoskeleton to the membrane, cytosolic and nuclear fractions. There was minimal evidence of a pro-inflammatory 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 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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