THE EVOLUTION OF BLOOD COAGULATION FACTOR VIII IN MAMMALS

对猴子、狗、猫、猪、牛、老鼠和虎鲸等多种哺乳动物的凝血能力进行了研究，并与人类的凝血能力进行了比较。除了猴子外，所有哺乳动物的凝血因子VIII(FVIII)活性水平都高于人类，这导致它们在血液凝固的内在途径中具有高凝状态。识别FVIII重链A1结构域的C5在猴中的交叉反应率为7%，在狗中为2.7%，在猫中为16.2%，在其他哺乳动物中为0。识别FVIII重链A2结构域的RFF/8在猕猴中的交叉反应性为1.3%，在其他动物中为0。识别FVIII轻链A3结构域的NMC-VIII/9在所有哺乳动物中均未观察到交叉反应。识别FVIII轻链C2结构域的NMC-VIII/9对猴、狗、猫、猪、猪的交叉反应率分别为54.5%、130%、82.8%、13.4%、0。这些数据表明，在大多数哺乳动物中，FVIII分子轻链上C2表位的立体结构被保存下来，C2表位是FVIII功能的重要区域。

The coagulability in various mammals; monkeys, dogs, cats, pigs, cattle, mice and a killer whale were studied as compared to that in human. The levels of factor VIII (FVIII) coagulant activity in all mammals but monkeys were higher than that in human, resulting in their hypercoagulability in the intrinsic pathway of blood coagulation.Cross-reactivity of monoclonal antibodies against various mammalian FVIII was determined as compared to human FVIII. The cross-reactivity of C5 which recognized A1 domain of FVIII heavy chain were 7 % in monkeys, 2.7 % in dogs, 16.2 % in cats, and 0 % in the other mammals. The cross-reactivity of RFF/8, which recognized A2 domain of FVIII heavy chain were 1.3 % in monkeys, and 0 % in the others. No cross-reactivity of NMC-VIII/9, which recognized A3 domain of FVIII light chain, was observed in all mammals. The cross-reactivity of NMC-VIII/9, which recognized C2 domain of FVIII light chain were 54.5 % in monkeys, 130 % in dogs, 82.8 % in cats, 13.4 % in pigs, 0 % in the others. These data suggest that the stereoscopic structure of C2 epitope in the light chain of FVIII molecule is preserved among most of mammals and that C2 epitope is very important region to FVIII function.