SEARCH:   Advanced

Blood, 1 March 2007, Vol. 109, No. 5, pp. 1984-1991. Prepublished online as a Blood First Edition Paper on October 17, 2006; DOI 10.1182/blood-2006-07-037945. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-07-037945v1 109/5/1984    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 Lay, A. J. Articles by Castellino, F. J. Search for Related Content PubMed PubMed Citation Articles by Lay, A. J. Articles by Castellino, F. J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Acute inflammation is exacerbated in mice genetically predisposed to a severe protein C deficiency Angelina J. Lay1, Deborah Donahue1, Meng-Ju Tsai1, and Francis J. Castellino1 1 W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN The anticoagulant, activated protein C (aPC), possesses antithrombotic, profibrinolytic, anti-inflammatory, and antiapoptotic properties, and the level of this protein is an important marker of acute inflammatory responses. Although infusion of aPC improves survival in a subset of patients with severe sepsis, evidence as to how aPC decreases mortality in these cases is limited. Because a total deficiency of PC shows complete neonatal lethality, no animal model currently exists to address the mechanistic relationships between very low endogenous aPC levels and inflammatory diseases. Here, we show for the first time that novel genetic dosing of PC strongly correlates with survival outcomes following endotoxin (LPS) challenge in mice. The data provide evidence that very low endogenous levels of PC predispose mice to early-onset disseminated intravascular coagulation, thrombocytopenia, hypotension, organ damage, and reduced survival after LPS challenge. Furthermore, evidence of an exacerbated inflammatory response is observed in very low PC mice but is greatly reduced in wild-type cohorts. Reconstitution of low-PC mice with recombinant human aPC improves hypotension and extends survival after LPS challenge. This study directly links host endogenous levels of PC with various coagulation, inflammation, and hemodynamic end points following a severe acute inflammatory challenge. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Schouten, W. J. Wiersinga, M. Levi, and T. van der Poll Inflammation, endothelium, and coagulation in sepsis J. Leukoc. Biol., March 1, 2008; 83(3): 536 - 545. [Abstract] [Full Text] [PDF] M. A. Kowalska, S. A. Mahmud, M. P. Lambert, M. Poncz, and A. Slungaard Endogenous platelet factor 4 stimulates activated protein C generation in vivo and improves survival after thrombin or lipopolysaccharide challenge Blood, September 15, 2007; 110(6): 1903 - 1905. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020