Immune complexes bind to cultured rat glomerular mesangial cells to stimulate superoxide release. Evidence for an Fc receptor.
Contractile mesangial cells (MC) possess a number of macrophage-like characteristics, including oxygen radical generation. We suggest that under certain conditions MC may serve as immune effector cells in glomerulonephritis. Immune complex (IC) deposits are a hallmark of glomerulonephritis. Because IC elicit oxygen radicals from other cell types and because oxygen radicals can induce glomerular injury, we measured release of O2- by cultured rat MC in response to IC and, in separate experiments, the binding of IC to MC. Soluble and insoluble IC markedly stimulated dose- and time-dependent, saturable O2- release. Specific antibody (Ab) alone or mixtures of nonimmune Ab and antigen had no significant effect. IC-induced O2- release was not affected by cytochalasin B, an inhibitor of phagocytosis. Binding studies with radioiodinated IC demonstrated specific binding with an affinity of 1.56 X 10(6) M-1 and 1.02 X 10(5) receptors per cell. Both binding and O2- release required the Fc region of Ab. IC formed with F(ab')2 fragments did not bind specifically to or stimulate O2- release by MC. Cultured cells from rats depleted of bone marrow-derived phagocytes by irradiation produced amounts of O2- similar to cells from normal rats. These results provide evidence that IC affect the biology of the contractile glomerular MC in a manner that is dependent on the Fc region of Ab and suggest that MC structure and function may be altered at sites of injury.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D002478:Cells, Cultured; D003572:Cytochalasins / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D005920:Glomerular Mesangium / Q000166:cytology / Q000502:physiology*; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007700:Kinetics; D008264:Macrophages / Q000276:immunology; D051381:Rats; D011961:Receptors, Fc / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*
D000936:Antigen-Antibody Complex; D003572:Cytochalasins; D007141:Immunoglobulin Fc Fragments; D011961:Receptors, Fc; D013481:Superoxides