凝血酶诱导人单核细胞分泌白细胞介素-6的分析

目的凝血酶通过蛋白酶激活受体（PARs）调节细胞的功能而在炎症和免疫反应中起重要作用，对于其诱导单核细胞产生细胞因子的报道则结果不-致。方法用凝血酶及PARs的激动肽分别激发高度纯化后的单核细胞16h后，用ELISA检测单核细胞培养上清液中的1L-6。结果凝血酶呈浓度依赖性地诱导单核细胞产生IL-6，当凝血酶酶活性被抑制后，诱导单核细胞产生IL-6的能力被抑制。PAR-1激动肽SFLI。R—NH2和PAR-4激动肽GYPGQV—NH2呈浓度依赖性地诱导单核细胞产生IL-6，PAR-1、PAR-4不能诱导单细胞产生IL-6，而PAR-3激动肽TFRGAP—NH2和反激动肽PAGRFr—NH2对于单核细胞产生IL-6无明显作用。结论凝血酶可以诱导高度纯化的成人外周血单核细胞产生IL-6，它们的作用依赖于酶的活性，说明它可能是通过PARs激活单核细胞。

Thrombin induces production of interleukin - 6by human monocytes

Objective Thrombin played an important role in inflammation and immune regulation by regulating cell functions via proteinase aetivated receptors （PARs）. However, little is known of the function of thrombin on humanmonocytes. Methods Highly purified monocytes were challenged for 16 hours with thrombin and agonist peptides of PARs, and measured the levels of interleukin （IL） - 6 in culture supematants of monocytes by ELISA. Results Thrombin provoked a dose dependent release of IL -6 from monocytes following 16 h incubation period. Thrombin inhibitor hirudin was able to inhibit thrombin induced secretion of IL - 6 from mouoeytes. SFLLR - NH2, GYPGQV - NH2 stimulated increase in IL - 6 secretion from monocytes following 16 h incubation, whereas its reverse peptide RLLFS - NH2 and VQGPYG - NH2 had little effects on IL -6 release. In contrast, TFRGAP - NH2 and its reverse peptide PAGRFT - NH2 showed little influence on IL - 6 release from monocytes following 16 h incubation period. Conclusion Thrombin are potent stimuli of IL -6 secretion from highly purified monocytes. Their actions on monocytes depend on their enzymatic activities and are likely through activation of PARs.