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

我们发现人类von Willebrand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。通过聚合酶链式反应(PCR)检测日本人的ABO血型，并探讨血型、血浆浓度与瑞斯托菌素和/或肉豆素诱导的vWF的血小板凝集活性之间的关系。血浆vWF浓度仅异种(AO，BO)显著低于同种(AA，BB)，提示vWF的转化率与vWF表面H(O)物质的表达存在一定的相关性。我们还发现IgM和Ig G与vWF相关，提示天然产生的抗血型抗原的抗体可能与vWF结合，因为这些浓缩物是从混合血浆中制备的。每种血型的血浆可以更有效地回收均匀的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。HPA和UEA分别识别vWF中的A型和H(O)血型物质。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。用HPA-琼脂糖柱从FVIII浓缩物中分离出富含A血型的VWF物质。利用该凝集素柱获得的血型特异性vWF，目前正在研究vWF的酶敏感性，以阐明血型物质在vWF中的生理作用。此外，我们正在收集不同血型亚型的个体以及不同血型之间骨髓移植的vWF血型表达的数据。

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.