title: An immobile subset of plasma membrane CD11b/CD18 (Mac-1) is involved in phagocytosis of targets recognized by multiple receptors.
abstract: CD11b/CD18 is a heterodimeric leukocyte surface receptor which functions in both C3bi-ligand binding and homotypic and heterotypic cell adherence. We have examined the effect of several anti-CD11b/18 mAb on phagocytosis of IgG (EIgG) or complement (EC4b) opsonized erythrocytes by polymorphonuclear leukocytes (PMN) and monocytes. F(ab')2 of two mAb (IB4, an anti-beta-chain mAb and Mo-1 an anti-alpha-chain mAb), inhibited both phagocytosis of EIgG and phorbol ester-stimulated phagocytosis of EC4b by PMN and monocytes. These F(ab')2 inhibited the binding of EIgG to monocytes, but they had no effect on binding of EIgG to PMN, or EC4b to either phagocyte. In addition, IB4 inhibited phorbol-ester stimulated phagocytosis of sheep E opsonized with C component 3bi (EC3bi) without inhibiting rosetting of these same targets. These data separate the anti-phagocytic effect of these mAb from effects on phagocyte-target adherence. When PMN were adherent to an anti-CD11b/CD18 F(ab')2-coated surface, EC3bi binding was abolished, but phagocytosis of EIgG or EC4b was unaffected. Subsequent addition of fluid- phase IB4 or Mo-1 F(ab')2 inhibited phagocytosis of EIgG or EC4b by the adherent cells. This suggested that the CD11b/CD18 involved in C3bi rosetting were mobile in the membrane, whereas those involved in phagocytosis of EIgG or EC4b were not. Cytochalasin treatment of PMN during adherence to F(ab')2-coated plates decreased both apical expression of CD11b/18 and subsequent ingestion of EIgG by 70%, suggesting that microfilaments are important in maintaining immobile CD11b/18 on the apical PMN surface. We conclude that there are functionally distinct populations of CD11b/CD18 on monocytes and PMN: one involved in C3bi rosetting and another involved in the process of phagocytosis mediated via several different receptors. CD11b/18 is not required for optimal target binding in all cases, but is always required for ingestion. As with several other integrins, the CD11b/18 molecules involved in phagocytosis have a functional association with the cell cytoskeleton.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: I L
authors.initials: IL
authors.lastname: Graham
authors.forename: H D
authors.initials: HD
authors.lastname: Gresham
authors.forename: E J
authors.initials: EJ
authors.lastname: Brown
mesh_terms: D000911:Antibodies, Monoclonal / Q000502:physiology; D000943:Antigens, Differentiation / Q000276:immunology*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology; D003179:Complement C3b / Q000378:metabolism; D003572:Cytochalasins / Q000494:pharmacology; D006801:Humans; D016177:Macrophage-1 Antigen; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis; D011956:Receptors, Cell Surface / Q000276:immunology*; D011951:Receptors, Complement / Q000276:immunology; D017463:Receptors, Complement 3b; D011961:Receptors, Fc / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D003572:Cytochalasins; D016177:Macrophage-1 Antigen; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D011961:Receptors, Fc; D003179:Complement C3b