Monocyte/macrophage Fc gamma RIII, unlike Fc gamma RIII on neutrophils, is not a phosphatidylinositol-linked protein.
The low affinity IgG Fc receptor, Fc gamma RIII, expressed on circulating neutrophils, natural killer (NK) cells, and tissue macrophages, is involved in effector functions such as cytotoxicity and immune complex clearance by these cells. While Fc gamma RIII is reported to be a phosphatidylinositol (PI)-linked, rather than peptide-linked, protein on neutrophils and NK cells, its membrane linkage in macrophages has not been studied. We examined the sensitivity of Fc gamma RIII to cleavage by PI-specific phospholipase C (PI-PLC) in cultured monocytes and alveolar tissue macrophages and report that this receptor is not PI-linked on these cells. We also observed normal levels of Fc gamma RIII on cultured monocytes of a patient with paroxysmal nocturnal hemoglobinuria, a disease in which PI-linked proteins are deficient. The results suggest that Fc gamma RIII occurs solely in a transmembrane form in cells of the monocyte/macrophage lineage. In addition, we studied Fc gamma RIII on a cloned NK cell line and found it to be resistant to the effects of PI-PLC under conditions that cleaved Fc gamma RIII on neutrophils. Taken together, our results provide evidence for a distinct form of Fc gamma RIII that differs from the neutrophil receptor in its structure and, possibly, in its function.
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia.
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Darby
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Chien
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Rossman
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Schreiber
D000943:Antigens, Differentiation / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000378:metabolism; D006801:Humans; D018950:Lipopolysaccharide Receptors; D008264:Macrophages / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000378:metabolism*; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism*; D017452:Receptors, IgG
D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D010716:Phosphatidylinositols; D011961:Receptors, Fc; D017452:Receptors, IgG; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase