Shen L, He X, Dahlbäck B
Department of Clinical Chemistry, Lund University, University Hospital, Malmö, Sweden.
Thromb Haemost. 1997 Sep;78(3):1030-6.
Human factor V has been shown not only to be a precursor to procoagulant factor Va but also to express anticoagulant properties. Thus, factor V was recently found to potentiate the effect of protein S as cofactor to activated protein C (APC) in the inactivation of the factor VIIIa-factor IXa complex. The purpose of this study was to determine whether the APC-cofactor function of factor V was also expressed in the bovine protein C system and to elucidate the molecular background for the species specificity of APC. For this purpose, the effects of protein S and factor V on APC-mediated inactivation of factor VIIIa were studied using purified APC, protein S and factor V of human and bovine origin. The factor VIIIa investigated here was part of a Xase complex (i.e. factor IXa, factor VIIIa, phospholipid and calcium) and the APC-mediated inhibition of factor VIIIa was monitored by the ability of the Xase complex to activate factor X. Synergistic APC-cofactor function of factor V and protein S was demonstrated in the bovine system. The effect of bovine APC was potentiated by bovine protein S but not by human protein S, whereas both human or bovine protein S stimulated the function of human APC. Factor V did not express species specificity in its APC-cofactor activity even though bovine factor V was more potent than its human counterpart. Recombinant human/bovine protein S chimeras were used to demonstrate that the thrombin sensitive region and first epidermal growth factor-like module of protein S determine the species specificity of the APC-protein S interaction. In conclusion, both human and bovine factor V were found to express APC-cofactor activity which depends on the presence of protein S. The species specificity of APC was shown to be caused by the interaction between APC and protein S.
人凝血因子V不仅已被证明是促凝因子Va的前体，还具有抗凝特性。因此，最近发现因子V在灭活因子VIIIa - 因子IXa复合物中作为活化蛋白C（APC）的辅因子增强蛋白S的作用。本研究的目的是确定因子V的APC辅因子功能在牛蛋白C系统中是否也有表达，并阐明APC物种特异性的分子背景。为此，使用人源和牛源的纯化APC、蛋白S和因子V，研究了蛋白S和因子V对APC介导的因子VIIIa灭活的影响。这里研究的因子VIIIa是Xase复合物（即因子IXa、因子VIIIa、磷脂和钙）的一部分，通过Xase复合物激活因子X的能力来监测APC介导的因子VIIIa抑制作用。在牛系统中证明了因子V和蛋白S具有协同的APC辅因子功能。牛APC的作用被牛蛋白S增强，但不被人蛋白S增强，而人或牛蛋白S均刺激人APC的功能。尽管牛因子V比人因子V更有效，但因子V在其APC辅因子活性方面不表现出物种特异性。使用重组人/牛蛋白S嵌合体证明，蛋白S的凝血酶敏感区和第一个表皮生长因子样结构域决定了APC - 蛋白S相互作用的物种特异性。总之，发现人源和牛源因子V均表达依赖于蛋白S存在的APC辅因子活性。APC的物种特异性被证明是由APC与蛋白S之间的相互作用引起的。
