期刊
BLOOD
卷 110, 期 6, 页码 1903-1905出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-03-081901
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资金
- NHLBI NIH HHS [P01 HL040387, HL084006, K23 HL092164, R01 HL084006, HL40387] Funding Source: Medline
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.
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