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Blood, 15 September 2007, Vol. 110, No. 6, pp. 1903-1905. Prepublished online as a Blood First Edition Paper on May 31, 2007; DOI 10.1182/blood-2007-03-081901. This Article Full Text (PDF) All Versions of this Article: blood-2007-03-081901v1 110/6/1903    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 Kowalska, M. A. Articles by Slungaard, A. Search for Related Content PubMed PubMed Citation Articles by Kowalska, M. A. Articles by Slungaard, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 27, 2007 Accepted May 24, 2007 Endogenous platelet factor 4 stimulates activated protein C generation in vivo and improves survival after thrombin or lipopolysaccharide challenge M. Anna Kowalska*, Shawn A. Mahmud, Michele P. Lambert, Mortimer Poncz, and Arne Slungaard Center for Medical Biology, Polish Academy of Science, Lodz, Poland Dept of Hematology, Oncology and Transplantation Medicine, University of Minnesota, Minneapolis, MN, United States Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, PA, United States Dept of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, United States * Corresponding author; email: kowalska{at}email.chop.edu. Pharmacologic infusion of activated protein C (APC) improves survival in severe sepsis, and platelet factor 4 (PF4) accelerates APC generation in a primate thrombin-infusion model. We now tested whether endogenous platelet PF4 content affects APC generation. Mice completely deficient in PF4 (mPF4-/-) had impaired APC generation and survival after thrombin infusion, similar to the impairment seen in heterozygote protein C-deficient (PC+/-) mice. Transgenic mice overexpressing human PF4 (hPF4+) had increased plasma APC generation. Overexpression of platelet PF4 compensated for the defect seen in PC+/- mice. In both a thrombin and a lipopolysaccharide (LPS) survival model, hPF4+ and PC+/-/hPF4+ mice had improved survival. Further, infusion of hPF4+ platelets improved survival of wildtype mice after an LPS challenge. These studies suggest that endogenous PF4 release may have biological consequences for APC generation and survival in clinical sepsis. Infusions of PF4-rich platelets may be an effective strategy to improve outcome in this setting. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. P. Lambert, Y. Wang, K. H. Bdeir, Y. Nguyen, M. A. Kowalska, and M. Poncz Platelet factor 4 regulates megakaryopoiesis through low-density lipoprotein receptor-related protein 1 (LRP1) on megakaryocytes Blood, September 10, 2009; 114(11): 2290 - 2298. [Abstract] [Full Text] [PDF] R. J. S. Preston, S. Tran, J. A. Johnson, F. N. Ainle, S. Harmon, B. White, O. P. Smith, P. V. Jenkins, B. Dahlback, and J. S. O'Donnell Platelet Factor 4 Impairs the Anticoagulant Activity of Activated Protein C J. Biol. Chem., February 27, 2009; 284(9): 5869 - 5875. [Abstract] [Full Text] [PDF]

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