Deficiency of a surface membrane glycoprotein (Mo1) in man.
Deficiency of a granulocyte surface glycoprotein of 150,000-D had been associated with defective C3- and IgG-dependent phagocytosis in a patient with recurrent bacterial infections. By using monoclonal antibodies, we found that this patient's granulocytes, monocytes, and null cells were deficient in Mo1 (equivalent to OKM1 and Mac-1), a cell surface molecule consisting of two noncovalently linked glycoproteins of 155,000 and 94,000 D. The 155,000-D subunit is closely associated with the human complement receptor that recognizes C3bi and/or a further degradation product termed C3dg (C3bi receptor); the 94,000-D subunit has been shown to be shared, on normal cells, by two other surface membrane glycoproteins: lymphocyte function-associated antigen-1 (LFA-1) and P-150, 95. Both subunits of Mo1 were deficient on the patient's granulocytes as determined by immunoprecipitation with subunit-specific monoclonal antibodies as well as fluorescence analysis. Mol-deficient monocytes, like granulocytes, had defective C3-and IgG-dependent phagocytosis. Natural killing activity by the patient's peripheral blood leukocytes was normal. Mo1-deficient granulocytes and monocytes rosetted normally with sheep erythrocytes coated with C3bi. This rosetting was totally inhibited by a mixture of anti-Mo1 and anti-C3b (the major fragment of C3) receptor antibodies but not by either antibody alone. Since monoclonal antibodies to the 155,000-D subunit of Mo1 can inhibit C3bi receptor binding, immune phagocytosis, opsonized zymosan-induced degranulation, and superoxide generation by normal phagocytes (functions which are defective in Mo1-deficient cells), it appears likely that Mo1 deficiency may in part underlie the functional aberrations leading to recurrent bacterial infections in man.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D000954:Antigens, Surface / Q000032:analysis* / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology*; D011232:Chemical Precipitation; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000032:analysis* / Q000276:immunology; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D010587:Phagocytosis; D011951:Receptors, Complement / Q000032:analysis; D011961:Receptors, Fc / Q000032:analysis
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D006023:Glycoproteins; D011951:Receptors, Complement; D011961:Receptors, Fc