C3 is central to the interstitial component of experimental immune complex glomerulonephritis

We have suggested that renal tubular synthesis of C3 and its activation in the cortical interstitium is a mechanism for the progression of glomerulonephritis to interstitial injury. To test this hypothesis, immune complex glomerulonephritis was induced in C57BL/6 mice by intraperitoneal injections of horse spleen apoferritin and lipopolysaccharide (HSA/LPS). When compared to wild-type (WT) animals, C3 knockout (C3KO) mice had glomerular changes that were identical. Morphometric analysis of the cortical interstitium, however, showed marked differences. WT mice had more interstitial inflammation, edema, and tubular atrophy, when compared to C3KO mice. At the end of the experiment, WT animals also had significantly more proteinuria than did C3KOs. These experiments provide further evidence of a role of locally synthesized complement in the progression of glomerular disease.