LIPOPOLYSACCHARIDE-STIMULATED LEUKOCYTES CONTRIBUTE TO PLATELET AGGREGATIVE DYSFUNCTION, WHICH IS ATTENUATED BY CATALASE IN RATS

作者:Dong Huei Ping; Chunag I Chun; Wang Dean Chuan; Huang Li Ju; Lee Chu I; Tsai Jen Hsiang; Yang Rei Cheng*
来源:The Kaohsiung Journal of Medical Sciences, 2010, 26(11): 584-592.
DOI:10.1016/S1607-551X(10)70090-5

摘要

Endotoxemia causes several hematological dysfunctions, including platelet degranulation or disseminated intravascular coagulation, which lead to thrombotic and hemorrhagic events. Here, we tested the hypothesis that bacterial lipopolysaccharide (LPS)-stimulated leukocytes contribute to platelet aggregative dysfunction, and this function is attenuated by antioxidants. Plateletrich plasma (PRP) was prepared from whole blood of normal and endotoxemic rats. The ability of platelet aggregation was measured by an aggregometer. LPS (50-100 mu g/mL) was incubated with PRP, whole blood and PRP with polymorphonuclear leukocytes (PMNs) for 30 minutes, 60 minutes and 90 minutes, and platelet aggregation was detected. LPS-induced platelet aggregative dysfunction was undetectable in intact PRY which was isolated from normal whole blood, whereas it was detected in PRP isolated from endotoxemic rats and LPS-treated whole blood. Moreover, the effect of LPS-induced platelet aggregative dysfunction on intact PRY was observed when the PMNs were added. LPS-induced platelet aggregative dysfunction was significantly attenuated by catalase alone and in combination with N(G)-nitro-L-arginine methyl ester, but not by N(G)-nitro-L-arginine methyl ester alone. These results indicate that LPS-stimulated PMNs modulate platelet aggregation during LPS treatment and the effects are reversed by antioxidants. PMNs serve as an approach to understand LPS-induced platelet aggregative dysfunction during endotoxemia. During this process, the generation of reactive oxygen species, hydrogen peroxide especially, from LPS-stimulated PMNs could be an important potential factor in LPS-induced platelet aggregative dysfunction. Catalase contributes to the prevention of platelet dysfunction during LPS-induced sepsis.