Modulation of fibrin clot formation by human serum amyloid P component (SAP) and heparin
Modulation of fibrin clot formation by human serum amyloid P component (SAP) and heparin
复制标题
人血清淀粉样蛋白 P 成分 (SAP) 和肝素对纤维蛋白凝块形成的调节
DOI：
--
复制
发表时间：
1983
影响因子：
15.3
通讯作者：
B. Fiedel
中科院分区：
文献类型：
--
作者：
C. Ku;B. Fiedel
血清淀粉样蛋白p组分（SAP）是人体正常的血浆成分，循环浓度约为40微克/毫升。据报道，SAP的超生理量（150-300微克/毫升）会影响凝血。我们通过研究在肝素存在和不存在的情况下SAP对凝块时间的影响进一步研究了这一点，肝素是一种建议的SAP配体，它本身是凝血过程的调节剂。在没有肝素的情况下，SAP（5-125微克/毫升）在正常柠檬酸血浆中对活化血栓法试剂、脑血栓活素、罗素毒蛇毒或凝血酶产生的凝块时间没有影响。然而，在肝素含量对凝块时间影响不大的情况下，SAP（5-40微克/毫升）大大延长了凝块形成时间，凝血酶时间对SAP最敏感。这表明SAP的主要作用在凝血途径的远端水平。放射免疫分析显示，SAP的超生理浓度（150-300微克/毫升）可使纤维蛋白原释放的纤维蛋白肽A （FPA）减少约25%。在肝素存在的情况下，观察到大量的协同作用，仅需要25-50微克/毫升的SAP，就可以最大限度地减少约70%的FPA生成。这种抑制与凝血酶凝块时间的增加有关，但与抗凝血酶III或活化因子XIII活性的任何直接调节无关，并且与纤溶率的改变无关。此外，虽然SAP本身不干扰自发纤维蛋白聚合过程，但在肝素存在下，聚合时间延长（大于145%）。我们认为这些数据反映了血清淀粉样蛋白P成分影响凝血的主要机制。
Serum amyloid P-component (SAP) is a normal plasma constituent in man with a circulating concentration of approximately 40 micrograms/ml. Supraphysiological amounts of SAP (150-300 micrograms/ml) have been reported to affect coagulation. We have investigated this further by studying the effect of SAP upon clot times in both the absence and presence of heparin, a suggested ligand for SAP and itself a modulator of coagulation processes. In the absence of heparin, SAP (5-125 micrograms/ml) had no effect on clot times generated by Activated Thrombofax Reagent, brain thromboplastin, Russell's Viper Venom or thrombin when assessed in normal citrated plasma. However, in the presence of amounts of heparin that had only a minor effect upon clot times, SAP (5-40 micrograms/ml) greatly prolonged clot formation, with the thrombin time the most sensitive to SAP. This suggested that the primary effect of SAP was at this distal level of the coagulation pathway. Evaluation by radioimmunoassay revealed that supraphysiological concentrations of SAP (150-300 micrograms/ml) alone reduced by approximately 25% the release of fibrinopeptide A (FPA) from fibrinogen. In the presence of heparin, substantial synergism was observed with maximal reductions of approximately 70% in FPA production requiring only 25-50 micrograms/ml SAP. This inhibition correlated with increased thrombin clot time but was unrelated to any direct modulation in either the activities of anti-thrombin III or activated Factor XIII, and was independent of an alteration in the rate of fibrinolysis. Further, while SAP itself did not interfere with the process of spontaneous fibrin polymerization, in the presence of heparin a prolonged polymerization time (greater than 145%) was observed. We believe that these data reflect the primary mechanisms by which serum amyloid P component influences blood coagulation.