Fc dependence of macrophage accumulation and subsequent injury in experimental glomerulonephritis.
An IgG-initiated, macrophage-mediated model of experimental glomerulonephritis was induced in rabbits. Experiments were designed to determine the importance of the Fc portion of this disease-initiating IgG antibody in inducing macrophage accumulation and subsequent proteinuria and histologic injury. The model was a passive model of the autologous phase of anti-glomerular basement membrane antibody-induced glomerulonephritis. Leukocyte depletion with nitrogen mustard prevented the development of proteinuria, macrophage accumulation, and histologic injury, but decomplementation with cobra venom had no effect, confirming leukocyte dependence but complement independence of injury in this model. The effect of equimolar kidney binding quantities of the intact disease-initiating IgG and an F(ab')2 fraction of this same antibody were compared. Intact IgG deposition was associated with heavy proteinuria (630 mg/24 hr, mean +/- 106 SD). A diffuse endocapillary proliferative glomerulonephritis with prominent macrophage accumulation (54 +/- 21 macrophages/glomerulus) developed. Deposition of the F(ab')2 fraction was associated with only minimal proteinuria (28 +/- 7 mg/24 hr). Histologic appearances showed no significant glomerulonephritis, and macrophage accumulation (4.1 +/- 0.6 macrophages/glomerulus) was substantially prevented. Thus, macrophage accumulation and subsequent injury in this model are dependent on the Fc portion of the disease-initiating IgG molecule. These data suggest immune adherence is an important mechanism for macrophage accumulation in antibody-initiated glomerulonephritis. Furthermore, the prevention of the Fc-dependent macrophage accumulation and simultaneous abrogation of injury suggest the lesion is mediated by macrophages.
D000818:Animals; D003165:Complement System Proteins / Q000172:deficiency; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D007668:Kidney / Q000378:metabolism; D007678:Kidney Glomerulus / Q000166:cytology / Q000276:immunology / Q000473:pathology; D007970:Leukopenia / Q000139:chemically induced; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008466:Mechlorethamine / Q000008:administration & dosage; D011507:Proteinuria / Q000209:etiology; D011817:Rabbits; D011961:Receptors, Fc
D011961:Receptors, Fc; D008466:Mechlorethamine; D003165:Complement System Proteins