Structure and function of ABO blood group antigens fond in human von Willebrand factor

人血管性血友病因子中ABO血型抗原的结构和功能

• 批准号: 06671118
• 负责人: MATSUI Taei
• 金额: $ 1.15万
• 依托单位: Institute for Comprehensive Medical Science, Fujita Health University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671118/
• 关键词: ABO Blood group; von Willebrand factor; FVIII Concentrate; Lectin; Protease; Bone marrow transplantation; PCR; Plasma glycoprotein; フォン・ビルブラント因子; ELISA; 凝固因子

We have found that human von Willebrand factor (vWF) has a unique characteristic of possessing covalently-linked ABO blood group antigens. We are interested in the physiological significance of these antigens in vWF.ABO blood group genotype in Japanese was determined by PCR and the relationship among the blood group genotype, plasma concentration and the ristocetin- and/or botrocetin-induced platelet agglutinating activity of vWF was surveyed. vWF concentration in plasma was only significantly lower in hetero (AO,BO) than homo (AA,BB), suggesting the presence of some correlation between the turnover ratio of vWF and the expression of H (O) substance on vWF.We surveyed blood group antigens in commercially available FVIII concentrates and found that only vWF and factor VIII shows antigenicity. We also found that IgM and IgG are associated with vWF,suggesting that naturally occurring antibodies against blood group antigen might be bound to vWF since these concentrates were prepared from pooled plasma. Plasma with each blood group may provide more efficient recovery of uniform vWF and FVIII.To isolate vWF of certain blood group from the concentrates, we examined several blood group specific lectins. HPA from Helix pomatia and UEA from Ulex europaeus recognized blood group A and H (O) substances in vWF,respectively. Other lectins were not sufficiently specific, though they show blood group specific hemagglutination. vWF rich in blood group A substance was separated from the FVIII concentrates by a HPA-agarose column. Using blood group specific vWF obtained by this lectin column, protease susceptibility of vWF is now being studied to elucidate the physiological funciton of blood group substances in vWF.Further, we are collecting data on the blood group expression of vWF in individuals with several blood group subtypes and with bone marrow transplantation between different blood groups.

我们发现人血管性血友病因子（vWF）具有一个独特的特性，即具有共价连接的ABO血型抗原。我们感兴趣的是这些抗原在vWF中的生理意义。ABO血型基因型在日本的PCR测定和血型基因型之间的关系，血浆浓度和ristoclavine和/或botrocetin诱导的血小板凝集活性的vWF进行了调查。血浆中vWF浓度仅在异源（AO，BO）中显著低于同源（AA，BB），提示vWF的周转率与vWF上H（O）物质的表达之间存在一定的相关性。我们还发现IgM和IgG与vWF相关，表明天然存在的抗血型抗原抗体可能与vWF结合，因为这些浓缩物是从合并血浆中制备的。为了从浓缩物中分离某些血型的vWF，我们检测了几种血型特异性凝集素。来自黑果蝠的HPA和来自欧洲荆豆的UEA分别识别vWF中的A血型和H（O）物质。其他凝集素没有足够的特异性，但它们显示血型特异性血凝。通过HPA-琼脂糖柱从FVIII浓缩物中分离富含血型A物质的vWF。目前正在利用该凝集素柱获得的血型特异性vWF，研究vWF的蛋白酶敏感性，以阐明vWF中血型物质的生理功能。此外，我们正在收集几种血型亚型个体和不同血型之间骨髓移植中vWF的血型表达数据。

项目成果

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