NDLI: Endogenous platelet factor 4 stimulates activated protein C generation in vivo and improves survival after thrombin or lipopolysaccharide challenge

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Endogenous platelet factor 4 stimulates activated protein C generation in vivo and improves survival after thrombin or lipopolysaccharide challenge

Content Provider	Scilit
Author	Kowalska, M. Anna Mahmud, Shawn Lambert, Michele P. Poncz, Mortimer Slungaard, Arne
Copyright Year	2007
Description	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 wild-type mice after an LPS challenge. These studies suggest that endogenous PF4 release may have biologic 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.
Related Links	http://www.bloodjournal.org/content/bloodjournal/110/6/1903.full.pdf
Ending Page	1905
Page Count	3
Starting Page	1903
DOI	10.1182/blood-2007-03-081901
Journal	Blood
Issue Number	6
Volume Number	110
Language	English
Publisher	American Society of Hematology
Publisher Date	2007-09-15
Access Restriction	Open
Subject Keyword	Research and Experimental Medicine Lipopolysaccharide Sepsis Thrombin Platelet Factor Endogenous Platelet Primate Pf4 Improved Survival Apc Journal: Blood (Vol- 90, Issue- 6)
Content Type	Text
Resource Type	Article

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