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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2350-2355. Prepublished online as a Blood First Edition Paper on November 2, 2004; DOI 10.1182/blood-2004-05-1963. This Article Full Text (PDF) All Versions of this Article: 2004-05-1963v1 105/6/2350    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Liu, D. Articles by Davis III, A. E Search for Related Content PubMed PubMed Citation Articles by Liu, D. Articles by Davis III, A. E Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 25, 2004 Accepted October 25, 2004 C1 inhibitor prevents gram negative bacterial lipopolysaccharide-induced vascular permeability Dongxu Liu, Dong Zhang, Jennifer Scafidi, Xiao Wu, Cort C Cramer, and Alvin E Davis III* CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA, USA Children's Hospital, Boston, MA, USA * Corresponding author; email: aldavis{at}cbr.med.harvard.edu. Gram negative bacterial endotoxemia may lead to the pathological increase of vascular permeability with systemic vascular collapse, a vascular leak syndrome, multiple organ failure (MOF), and/or shock. Previous studies demonstrated that C1 inhibitor (C1INH) protects mice from LPS-induced lethal septic shock via a direct interaction with lipopolysaccharide (LPS). Here, we report that C1INH blocked the LPS-induced increase in transendothelial flux through an endothelial monolayer. In addition, LPS-mediated detachment of cultured endothelial cells was prevented with C1INH. C1INH also inhibited LPS-induced endothelial cell apoptosis as demonstrated by suppression of DNA fragmentation and annexin V expression. As illustrated by laser scanning confocal microscopy, C1INH completely blocked the binding of FITC-LPS to human umbilical vein endothelial cells (HUVEC). C1INH protected from localized LPS-induced increased plasma leakage in C57BL/6J mice and in C1INH deficient mice. Local vascular permeability in response to LPS was increased to a greater extent in C1INH deficient mice in comparison with wild type littermate controls and was reversed by treatment with C1INH. Systemic administration of LPS to mice resulted in increased vascular permeability, which was reduced by C1INH. Therefore, these studies demonstrate that C1INH, in addition to its role in suppression of LPS-mediated macrophage activation, may play an important role in the prevention of LPS-mediated increased vascular permeability, endothelial cell injury, and multiple organ failure. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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