Analysis of structure and function of sugar chains included in Fc receptor

鼠巨噬细胞系P388 D1表达识别与抗原结合的IgG的Fc部分的Fc受体，但不能摄取抗原-抗体复合物。然而，细胞表面糖链的修饰可以诱导Fc受体介导的吞噬作用，而不影响乳胶珠的非特异性吞噬作用。因此，认为Fc受体在结构上被修饰以表达其功能。为了证明这种可能性，我们建立了不同类型的修饰糖链结构的试剂诱导吞噬的体外系统。通过使用该系统，获得了以下结果。（1）糖基化诱导的吞噬功能改变是由Fcr 2b受体介导的。（2）该受体的糖链在诱导吞噬作用后发生了变化。（3）这种结构变化影响了与受体结合的配体的摄取，但不影响配体与受体的结合。(4)I?结构改变的受体的配体的结合诱导了包括Fc受体本身在内的细胞蛋白的磷酸化、花生四烯酸从细胞中的释放以及负责花生四烯酸释放的磷脂酶A2的活化。（5）花生四烯酸代谢抑制剂可抑制蛋白质磷酸化和吞噬作用，提示Fc受体糖基化改变通过激活花生四烯酸代谢和蛋白质磷酸化，影响吞噬作用的摄取过程，从而诱导Fc受体介导的吞噬作用。

A murine macrophage cell line, P388Dl, expresses Fc receptors which recognize Fc portion of IgG bound to antigen, but is not able to ingest the antigen-antibody complex. However, modification of cell surface sugar chains can induce Fc receptor-mediated phagocytosis without affecting nonspecific phagocytosis of latex beads. It is considered, therefore, that Fc receptors are structurally modified to express their function. To prove this possibility, the in vitro system for induction of phagocytosis by different kinds of reagents which modify structures of sugar chains was established. By using this system, the following results were obtained. (1)Altered glycosylation-induced phagocytosis was mediated by Fcr2b receptor. (2)The sugar chains of this receptor actually changed after induction of phagocytosis. (3)This structural change affected the ingestion of ligands bound to the receptor, but not the binding of ligands to the receptor. (4)I?inding of ligands to the structurally altered receptor induced phosphorylation of cellular proteins including Fc receptor itself, the release of arachidonic acid from the cells, and activation of phospholipase A2 responsible for arachidonic acid release. (5)Addition of inhibitors of arachidonic acid metabolism to the culture media of induced cells suppressed protein phosphorylation and phagocytosis.Thus, the results suggest that altered glycosylation of Fc receptor affects the ingestion process of phagocytosis by activating arachidonic acid metabolism and protein phosphorylation, resulting in the induction of Fc receptor-mediated phagocytosis.