Inhibition of Nephritic Factor-Dependent C3 Convertase: Isolation of a Natural Inhibitor of C3 Conversion from the Serum of a Patient with Nephritic Factor and Nephritis

Abstract

Abstract One patient with membranoproliferative glomerulonephritis (MPGN Type II), known to have nephritic factor (NF), was incidently found to have no C3 convertase activity in his serum. The negative serum, in fact, yielded high amounts of Mg++ dependent C3 convertase activity after fractionation. The inhibitory factor(s) (INH) was found to be a dialyzable, heat-stable substance filtering through a Sephadex G-50 with an apparent molecular weight of 4000 daltons. In the presence of INH, Inulin (12 mg/ml), semi-purified P̄ (DEAE and SPC 25 Sephadex preparation) and NF (DEAE, SPC 25 and Sephadex G-200 preparation) from different sources are incapable of converting C3. CoVF-induced C3 conversion is inhibited only with low concentration of the activator (less than 10 µg/ml). ZX (zymozan incubated with C2-deficient serum for 5 minutes at 18°C and washed) which converts 8 µg purified C3-EDTA in 10 minutes at 27°C, is totally inactive when INH is added during the formation of the insoluble C3 convertase.