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首页> 外文期刊>Infection and immunity >Platelet-activating factor modulates endotoxin-induced macrophage procoagulant activity by a protein kinase C-dependent mechanism.
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Platelet-activating factor modulates endotoxin-induced macrophage procoagulant activity by a protein kinase C-dependent mechanism.

机译：血小板活化因子通过蛋白激酶C依赖性机制调节内毒素诱导的巨噬细胞促凝活性。

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摘要

Macrophage procoagulant activity is an important mediator of extravascular fibrin deposition at sites of infection and appears to contribute to the pathogenesis of several infectious disease processes. Previous studies have shown that the inflammatory mediator platelet-activating factor was able to prime macrophages for induction of procoagulant activity by bacterial lipopolysaccharide. The present studies were designed to examine the mechanism of this priming effect. Platelet-activating factor (100 nM) primed macrophages for procoagulant activity generation in response to endotoxin at concentrations as low as 100 ng/ml and also following exposure to Escherichia coli, Bacteroides fragilis, and Staphylococcus aureus. The priming effect occurred following a pretreatment with platelet-activating factor for as short as 1 min, suggesting a rapid activation event. Two different doses of the calcium ionophore ionomycin were used to mimic the peak and sustained effects of platelet-activating factor on cytoplasmic calcium levels (1 microM and 100 nM, respectively). Neither dose was able to mimic the priming effect. However, extracellular calcium was necessary for induction of procoagulant activity and the priming effect. By contrast, the protein kinase C agonist phorbol myristate acetate reproduced the priming phenomenon observed for platelet-activating factor. In further support of the concept that protein kinase C activation mediated the effect of platelet-activating factor, the specific protein kinase C inhibitor staurosporine reversed the ability of platelet-activating factor to augment induction of macrophage procoagulant activity by endotoxin. These data suggest mechanisms by which inflammatory mediators within the microenvironment of infection might modulate the host response to bacterial pathogens.
机译：巨噬细胞促凝活性是血管外纤维蛋白在感染部位沉积的重要介质，并且似乎有助于几种传染病过程的发病机理。先前的研究表明，炎症介质血小板活化因子能够引发巨噬细胞，以通过细菌脂多糖诱导促凝活性。本研究旨在检查这种启动效应的机制。血小板活化因子（100 nM）引发巨噬细胞产生促凝活性，响应浓度低至100 ng / ml的内毒素，并且也暴露于大肠杆菌，脆弱拟杆菌和金黄色葡萄球菌后产生促凝活性。在用血小板活化因子预处理后短至1分钟就发生了启动效应，表明发生了快速活化事件。使用两种不同剂量的钙离子载体离子霉素来模拟血小板活化因子对细胞质钙水平的峰值和持续作用（分别为1 microM和100 nM）。两种剂量都不能模仿启动作用。然而，细胞外钙对于诱导促凝活性和引发作用是必需的。相比之下，蛋白激酶C激动剂佛波醇肉豆蔻酸酯乙酸盐再现了观察到的血小板激活因子的启动现象。为了进一步支持蛋白激酶C激活介导血小板激活因子的作用这一观点，特定的蛋白激酶C抑制剂星形孢菌素逆转了血小板激活因子增强内毒素诱导巨噬细胞促凝活性的能力。这些数据表明感染的微环境内的炎症介质可能调节宿主对细菌病原体反应的机制。

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