Human macrophages kill human mesangial cells by Fas-L-induced apoptosis when triggered by antibody via CD16.
Glomerulonephritis may be triggered by antibody deposits that activate macrophages to promote tissue damage. Macrophage-induced apoptosis of human vascular smooth muscle cells and rodent mesangial cells is potentially relevant to glomerulonephritis. Therefore, studies of macrophage-induced apoptosis were extended to antibody-activated macrophages. That is, we studied antibody dependent cellular cytotoxicity (ADCC). To corroborate results, we studied biochemical versus microscopic measurements, soluble or immobilized immunoglobulin and vascular smooth muscle cells (VSMCs) or mesangial cells (MCs). U937 macrophages and human peripheral blood macrophages provoked antibody-dependent killing of MCs and VSMCs. Macrophage-induced death was apoptotic based on electron microscopy, annexin-V, activated caspase-3 and hypodiploid DNA. ADCC was inhibited by antagonistic antibodies to Fas-L and to CD16 (Fc-gamma-RIII) but not to CD64 (Fc-gamma-RI). In conclusion, antibody-dependent killing of human MCs by human macrophages was via Fas-L and CD16.
Boyle
J J
JJ
Department of Histopathology, Faculty Of Medicine, Imperial College London, UK. joseph.boyle@imperial.ac.uk
D000906:Antibodies / Q000276:immunology*; D017209:Apoptosis; D053222:Fas Ligand Protein; D005920:Glomerular Mesangium / Q000276:immunology* / Q000648:ultrastructure; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D010587:Phagocytosis; D017452:Receptors, IgG / Q000276:immunology*; D020298:U937 Cells
D000906:Antibodies; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D017452:Receptors, IgG