Freeman S D, Kelm S, Barber E K, Crocker P R
Molecular Haemopoiesis Laboratory, Imperial Cancer Research Fund (ICRF), University of Oxford, John Radcliffe Hospital, Headington, UK.
Blood. 1995 Apr 15;85(8):2005-12.
CD33 is a member of the Ig superfamily that is restricted to cells of the myelomonocytic lineage but whose functions and binding properties are unknown. It shares sequence similarity with sialoadhesin, CD22, and the myelin-associated glycoprotein, which constitute the Sialoadhesin family of sialic acid-dependent cell adhesion molecules. In the present study, we show that CD33 is a fourth member of this family. As a model for sialic acid-dependent binding, human erythrocytes were derivatized with N-acetylneuraminic acid (NeuAc) in different linkages. A recombinant soluble form of CD33, Fc-CD33, bound red blood cells with a specificity similar to that of sialoadhesin, preferring NeuAc alpha 2,3Gal in N- and O-glycans over NeuAc alpha 2,6Gal in N-glycans. Fc-CD33 also bound selectively to the myeloid cell lines HL-60 and U937. However, CD33 was unable to mediate cell binding after transient expression in COS cells, despite high levels of surface expression. Pretreatment of the CD33-transfected cells with sialidase rendered them capable of mediating sialic acid-dependent binding. These results show that CD33 can function as a sialic acid-dependent cell adhesion molecule and that binding can be modulated by endogenous sialoglycoconjugates when CD33 is expressed in a plasma membrane.
CD33是免疫球蛋白超家族的成员，它仅限于髓单核细胞系细胞，但其功能和结合特性尚不清楚。它与唾液酸粘附素、CD22和髓鞘相关糖蛋白具有序列相似性，它们构成了唾液酸依赖性细胞粘附分子的唾液酸粘附素家族。在本研究中，我们表明CD33是该家族的第四个成员。作为唾液酸依赖性结合的模型，人红细胞用不同连接方式的N-乙酰神经氨酸（NeuAc）进行衍生化。重组可溶性形式的CD33，即Fc-CD33，以与唾液酸粘附素相似的特异性结合红细胞，相比于N-聚糖中的NeuAcα2,6Gal，它更倾向于N-聚糖和O-聚糖中的NeuAcα2,3Gal。Fc-CD33也选择性地结合髓系细胞系HL-60和U937。然而，尽管在COS细胞中瞬时表达后CD33在表面有高水平表达，但它仍无法介导细胞结合。用唾液酸酶预处理CD33转染的细胞使其能够介导唾液酸依赖性结合。这些结果表明，CD33可以作为一种唾液酸依赖性细胞粘附分子发挥作用，并且当CD33在质膜中表达时，其结合可被内源性唾液酸糖缀合物调节。
