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Prepublished online as a Blood First Edition Paper on April 24, 2003; DOI 10.1182/blood-2002-12-3880. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3880v1 102/4/1499    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 Sturn, D. H. Articles by Wiedermann, C. J. Search for Related Content PubMed PubMed Citation Articles by Sturn, D. H. Articles by Wiedermann, C. J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Phagocytes Cell Adhesion and Motility Gene Expression Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 August 2003, Vol. 102, No. 4, pp. 1499-1505 PHAGOCYTES Expression and function of the endothelial protein C receptor in human neutrophils Daniel H. Sturn, Nicole C. Kaneider, Clemens Feistritzer, Angela Djanani, Kenji Fukudome, and Christian J. Wiedermann From the Division of General Internal Medicine, Department of Internal Medicine, University of Innsbruck, Austria; and the Department of Immunology, Saga Medical School, Nabeshima, Japan. Activation of protein C by thrombin bound to thrombomodulin is enhanced by endothelial protein C receptor. This pathway may inhibit inflammation. We investigated effects of protein C and activated protein C on neutrophils as well as whether an endothelial protein C receptor is involved in mediating protein C effects. Neutrophils were from venous blood of healthy donors. Cell migration, respiratory burst, phagocytic activity, and apoptosis were studied by micropore filter assays and fluorometry. Receptor expression was investigated by reverse transcriptase–polymerase chain reaction (PCR) for mRNA, sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography of immunoprecipitated receptor protein, and fluorescence-activated cell-sorter scanner (FACS) analysis using the anti–endothelial protein C receptor antibody RCR-252. Neither protein C nor activated protein C induced migration, yet both of them inhibited neutrophil chemotaxis triggered by interleukin-8, formyl-Met-Leu-Phe, antithrombin, or C5a. A protein C activation–blocking antibody against endothelial protein C receptor diminished inhibitory effects of protein C or activated protein C on migration. No effect of either protein C preparation was seen in neutrophil's respiratory burst, bacterial phagocytosis, or apoptosis assays. Endothelial protein C receptor immunoreactivity was confirmed on neutrophils by FACS. De novo synthesis is suggested by endothelial protein C receptor mRNA expression as demonstrated by reverse transcriptase PCR and immunoprecipitation SDS-PAGE analyses. Data suggest that an endothelial protein C receptor is expressed by human neutrophils whose active site ligation with either protein C or activated protein C arrests directed cell migration. Inhibitory effects of these components of the protein C pathway on neutrophil function may play a role in the protein C–based treatment of severe sepsis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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