Augmentation of macrophage complement receptor function in vitro. IV. The lymphokine that activates macrophage C3 receptors for phagocytosis binds to a fucose-bearing glycoprotein on the macrophage plasma membrane.

Macrophage receptors for the third component of complement (C3) are normally immobilized and unable to diffuse within the cell's plasma membrane and, even though they promote avid particle binding, are unable to promote phagocytosis of C3-coated particles. We have previously identified a lymphokine that activates macrophage C3 receptors for phagocytosis and have found that it acts by freeing the receptors so that they can diffuse within the macrophage plasma membrane. It seemed likely to us that the initial lymphokine-macrophage interaction would occur at the macrophage surface, perhaps via a specific lymphokine receptor. Since the binding of many ligands to cells is mediated by cell surface glycoproteins, we examined the protein and sugar requirements for murine peritoneal macrophages to respond to the lymphokine. Macrophages treated with the neutral protease Dispase lost the ability to respond to the lymphokine, and inclusion of L-fucose in the incubation medium containing lymphokine and macrophages inhibited markedly the macrophages' response to the lymphokine, suggesting that the lymphokine exerts its effects by first binding to fucose residues on a glycoprotein receptor on the macrophage surface. Further evidence for the essential role of macrophage surface fucose was obtained by demonstrating that pretreatment of macrophages with either fucosidase or gorse lectin, a fucose-binding lectin, strikingly disabled the cells from responding to the lymphokine. All treatments that prevented lymphokine activation of macrophage C3 receptors for phagocytosis also prevented lymphokine-induced C3 receptor mobility. These results strongly suggest that the lymphokine binds to a fucose-bearing macrophage surface glycoprotein, perhaps a specific lymphokine receptor. They also strengthen our hypothesis that, for a receptor to be able to promote phagocytosis, it must be able to diffuse within the macrophage plasma membrane.