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Immune complexes bind to cultured rat glomerular mesangial cells to stimulate superoxide release. Evidence for an Fc
Abstract:
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.
Insights
Contractile mesangial cells (MC) generate oxygen radicals when exposed to immune complexes (IC). This suggests MC may act as immune effector cells in glomerulonephritis, a finding dependent on the antibody
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Contractile mesangial cells (MC) exhibit macrophage-like properties, including oxygen radical generation.
- Immune complex (IC) deposition is characteristic of glomerulonephritis and can trigger inflammatory responses.
- Oxygen radicals are implicated in glomerular injury, necessitating investigation into their cellular sources.
Purpose of the Study:
- To investigate the role of contractile mesangial cells (MC) as potential immune effector cells in glomerulonephritis.
- To determine if cultured rat MC release oxygen radicals (O2-) in response to immune complexes (IC).
- To analyze the binding characteristics of IC to MC and the underlying mechanisms.
Main Methods:
- Cultured rat MC were exposed to soluble and insoluble IC.
- Oxygen radical release (O2-) was measured using dose- and time-dependent assays.
- Specific binding of radioiodinated IC to MC was quantified.
- Experiments utilized cytochalasin B and F(ab')2 fragments to probe mechanisms.
- MC from irradiated rats (depleted of phagocytes) were used for comparison.
Main Results:
- Soluble and insoluble IC significantly stimulated dose- and time-dependent O2- release from MC.
- Specific binding of IC to MC occurred with a defined affinity and receptor number.
- Both IC binding and O2- release were dependent on the Fc region of the antibody.
- Inhibition of phagocytosis did not affect IC-induced O2- release.
- MC from phagocyte-depleted rats showed similar O2- release, indicating MC are the source.
Conclusions:
- Contractile mesangial cells (MC) actively release oxygen radicals in response to immune complexes (IC).
- This response is mediated by the Fc region of antibodies and is independent of phagocytosis.
- MC possess characteristics suggesting they can function as immune effector cells in glomerulonephritis.
- Immune complex interactions can alter MC biology and potentially contribute to glomerular injury.

