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

我们发现人类血管性血友病因子（vWF）具有共价连锁ABO血型抗原的独特特征。我们对这些抗原在vWF中的生理意义很感兴趣。采用聚合酶链反应（PCR）测定日本人ABO血型基因型，并探讨血型基因型、血药浓度与雷斯托霉素和/或肉毒杆菌素诱导的vWF血小板凝集活性的关系。异种鼠（AO、BO）血浆中vWF浓度仅显著低于同种鼠（AA、BB），提示vWF的周转率与vWF上H (O)物质的表达存在一定的相关性。我们调查了市售FVIII浓缩物中的血型抗原，发现只有vWF和因子VIII具有抗原性。我们还发现IgM和IgG与vWF相关，这表明自然产生的抗血型抗原抗体可能与vWF结合，因为这些浓缩物是从汇集的血浆中制备的。不同血型的血浆可以更有效地恢复均匀的vWF和FVIII。为了从浓缩物中分离出特定血型的vWF，我们检测了几种血型特异性凝集素。来自双头莲的HPA和来自欧洲双头莲的UEA分别识别了vWF中的血型A和H (O)物质。其他凝集素没有足够的特异性，尽管它们显示出血型特异性的血凝。hpa -琼脂糖柱从FVIII浓缩物中分离出富含A型血物质的vWF。利用该凝集素柱获得的血型特异性vWF，目前正在研究vWF的蛋白酶敏感性，以阐明血型物质在vWF中的生理功能。此外，我们正在收集几种血型亚型和不同血型骨髓移植个体中vWF的血型表达数据。

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.