THE EVOLUTION OF BLOOD COAGULATION FACTOR VIII IN MAMMALS

哺乳动物凝血因子 VIII 的进化

• 批准号: 12670771
• 负责人: TANAKA Ichiro
• 金额: $ 2.05万
• 依托单位: NARA MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670771/
• 关键词: FACTOR VIII; MAMMALS

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.

研究了各种哺乳动物（猴、狗、猫、猪、牛、小鼠和虎鲸）的凝血能力，并与人类进行了比较。除猴外，其他哺乳动物的凝血因子VIII（FVIII）活性均高于人，导致其内源性凝血途径的高凝状态。识别FVIII重链A1结构域的C5的交叉反应性在猴中为7%，在犬中为2.7%，在猫中为16.2%，在其他哺乳动物中为0%。RFF/8识别FVIII重链A2结构域，在猴中的交叉反应性为1.3%，在其他动物中为0%。在所有哺乳动物中均未观察到识别FVIII轻链A3结构域的NMC-VIII/9的交叉反应性。NMC-VIII/9识别FVIII轻链C2结构域，在猴中的交叉反应性为54.5%，在犬中为130%，在猫中为82.8%，在猪中为13.4%，在其他动物中为0%。这些数据表明，在大多数哺乳动物中，FVIII分子轻链中的C2表位的立体结构是保留的，并且C2表位是FVIII功能的非常重要的区域。

项目成果

Nogami K., Tanaka I. et al: "Roll of factor VIII C2 domain in factor VII ding to factor Xa"Journal of Biological Chemistry. 274. 31000-31007 (1999)

Nogami K.、Tanaka I.等人：“Roll of Factor VIII C2 domain in Factor VII ding to Xa”Journal of Biological Chemistry。

Matsumoto T., Tanaka I. et al: "Immunological characterization of factor VIII autoantibodies in patients with acquired hemophilia A in the presence or absence of underlying disease"Thrombosis Research. 104. 381-388 (2001)

Matsumoto T.、Tanaka I. 等人：“在存在或不存在基础疾病的情况下获得性 A 型血友病患者中因子 VIII 自身抗体的免疫学特征”血栓形成研究。

Nogami K, Tanaka I, 他9名: "Rohe of factor VIIIC2 domain in factor VIII binding to factor Za"Journal of Biological Chemistry. 274. 31000-31007 (1999)

Nogami K、Tanaka I 和其他 9 人：“因子 VIII 中因子 VIIIC2 结构域与因子 Za 结合的 Rohe”《生物化学杂志》274. 31000-31007 (1999)。

K.Nogami,I.Taraka 他9名: "Identification of a factor VIII peptide, residues 2315-2330, which neutralizes human factor VIII C2 Inhibition alloantibodies"British Journal of Haematology. 107. 196-203 (1999)

K. Nogami、I. Taraka 和其他 9 人：“中和人因子 VIII C2 抑制同种抗体的因子 VIII 肽，残基 2315-2330 的鉴定”英国血液学杂志 107. 196-203 (1999)。

Shibata M, Tanaka I, 他11名: "An alloantibody recoguizing the FVIII A1 Domain in a patiant with CRM redoced hemoplulcin A in cohom the coresponding DNA sequsnce is deleted"Thrombosis and Haemostasis. 84. 442-448 (2000)

Shibata M、Tanaka I 和其他 11 人：“用 CRM 重新编码的血红蛋白 A 识别患者体内 FVIII A1 结构域的同种抗体，其中相应的 DNA 序列被删除”《血栓形成和止血》84. 442-448 (2000)。