ABO blood group glycans modulate sialic acid recognition on erythrocytes
ABO blood group glycans modulate sialic acid recognition on erythrocytes
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DOI：
10.1182/blood-2009-06-227041
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发表时间：
2009-10-22
期刊：
影响因子：
20.3
通讯作者：
Varki, Ajit
中科院分区：
文献类型：
--
作者：
Cohen, Miriam;Hurtado-Ziola, Nancy;Varki, Ajit
ABH（O）血型多态性是基于人类和其他灵长类动物中性血细胞表面聚糖结构的众所周知的种内变异。虽然针对这些聚糖的天然抗体可以作为输血和移植的屏障，但这种长期存在的进化多态性的正常功能在很大程度上仍然未知。虽然微生物的相互作用被认为是一种选择性的力量，但致命病原体与ABH抗原的直接结合还没有报道。我们在这项研究中表明，在人红细胞上发现的ABH抗原调节3种唾液酸识别蛋白（人Siglec-2、1918 SC流感血凝素和黑接骨木凝集素）与同一细胞表面上的唾液酸化聚糖的特异性相互作用。使用特定的糖基化酶，转换A和B聚糖的基本H（O）结构，我们显示ABH抗原稳定唾液酸化聚糖簇红细胞膜上独特的每种血型，产生不同的相互作用的3种唾液酸结合蛋白与红细胞从每种血型。我们进一步表明，通过稳定这种结构ABH抗原也可以调节唾液酸介导的相互作用的病原体，如恶性疟原虫疟疾寄生虫。因此，ABH抗原可以非共价地改变其他细胞表面聚糖向同源物结合蛋白的呈递，而自身不是直接配体。（血。2009;114：3668-3676）
ABH(O) blood group polymorphisms are based on well-known intraspecies variations in structures of neutral blood cell surface glycans in humans and other primates. Whereas natural antibodies against these glycans can act as barriers to blood transfusion and transplantation, the normal functions of this long-standing evolutionary polymorphism remain largely unknown. Although microbial interactions have been suggested as a selective force, direct binding of lethal pathogens to ABH antigens has not been reported. We show in this study that ABH antigens found on human erythrocytes modulate the specific interactions of 3 sialic acid-recognizing proteins (human Siglec-2, 1918SC influenza hemagglutinin, and Sambucus nigra agglutinin) with sialylated glycans on the same cell surface. Using specific glycosidases that convert A and B glycans to the underlying H(O) structure, we show ABH antigens stabilize sialylated glycan clusters on erythrocyte membranes uniquely for each blood type, generating differential interactions of the 3 sialic acid-binding proteins with erythrocytes from each blood type. We further show that by stabilizing such structures ABH antigens can also modulate sialic acid-mediated interaction of pathogens such as Plasmodium falciparum malarial parasite. Thus, ABH antigens can noncovalently alter the presentation of other cell surface glycans to cognate-binding proteins, without themselves being a direct ligand. (Blood. 2009;114:3668-3676)