Distinctive regulation of contact activation by antithrombin and C1-inhibitor on activated platelets and material surfaces
Distinctive regulation of contact activation by antithrombin and C1-inhibitor on activated platelets and material surfaces
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DOI：
10.1016/j.biomaterials.2009.07.052
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发表时间：
2009-12-01
期刊：
影响因子：
14
通讯作者：
Nilsson, Bo
中科院分区：
文献类型：
--
作者：
Back, Jennie;Lang, Markus Huber;Nilsson, Bo
活化的人血小板触发因子XII（FXII）介导的接触激活，这导致因子XIa - 抗凝血酶（AT）和因子XIa - 抗凝血酶复合物的产生。这表明在涉及生物材料与血液接触的治疗过程中，接触激活发生在不同部位，即活化的血小板和材料表面，并且受到不同的调节。在此我们表明，玻璃、高岭土和多聚磷酸盐在贫血小板血浆、富血小板血浆（PRP）和全血中诱导的激活产生高水平的因子XIIa - C1抑制剂（C1INH）、低水平的因子XIa - C1INH和激肽释放酶（KK）- C1INH，并且几乎没有抗凝血酶复合物。在PRP和血液中，血小板激活导致因子XIIa - 抗凝血酶、因子XIa - 抗凝血酶和激肽释放酶 - 抗凝血酶的形成，但几乎没有C1INH复合物。在严重创伤患者中，因子XIIa - 抗凝血酶和因子XIa - 抗凝血酶与活化血小板释放血小板反应蛋白 - 1（TSP - 1）相关。相反，当因子XIIa - 抗凝血酶水平较低时，可检测到因子XIIa - C1INH复合物。在因子XIIa - C1INH与因子XIIa - 抗凝血酶或TSP - 1之间未发现相关性。还表明抑制材料表面的因子XIIa会影响聚集血小板的功能。总之，因子XIIa - 抗凝血酶和因子XIIa - C1INH复合物的形成有助于区分由生物材料表面触发的接触激活和由活化血小板触发的接触激活。血小板聚集研究还表明，血小板功能受材料表面介导的接触激活的影响，并且因子XIIa - 抗凝血酶复合物的产生可能作为在使用生物材料装置的治疗过程中血栓反应的一种新的生物标志物。（C）2009由爱思唯尔有限公司出版
Activated human plate lets trigger FXII-mediated contact activation, which leads to the generation of FXIla-antithrombin (AT) and FXIa-AT complexes. This suggests that contact activation takes place at different sites, on activated platelets and material surfaces, during therapeutic procedures involving biomaterials in contact with blood and is differentially regulated. Here we show that activation in platelet-poor plasma, platelet-rich plasma (PRP), and whole blood induced by glass, kaolin, and polyphosphate elicited high levels of FXIIa-C1-inhibitor (C1INH), low levels of FXIa-C1INH and KK-C1INH, and almost no AT complexes. Platelet activation, in both PRP and blood, led to the formation of FXIIa-AT, FXIa-AT, and kallikrein (KK)-AT but almost no C1INH complexes. In severe trauma patients, FXIIa-AT and FXIa-AT were correlated with the release of thrombospondin-1 (TSP-1) from activated platelets. In contrast, FXIIa-C1INH complexes were detected when the FXIIa-AT levels were low. No correlations were found between FXIIa-C1INH and FXIIa-AT or TSP-1. Inhibition of FXIIa on material surfaces was also shown to affect the function of aggregating platelets. In conclusion, formation of FXIIa-AT and FXIIa-C1INH complexes can help to distinguish between contact activation triggered by biomaterial surfaces and by activated platelets. Platelet aggregation studies also demonstrated that platelet function is influenced by material surface-mediated contact activation and that generation of FXIIa-AT complexes may serve as a new biomarker for thrombotic reactions during therapeutic procedures employing biomaterial devices. (C) 2009 Published by Elsevier Ltd.