Publications

We have examined the ability of rat mesangial cells to regulate neutral proteinase production in vitro. Mesangial cells constitutively produced gelatinase when cultured in serum-free medium, and enzyme production by these cells was inhibited by cycloheximide. Coculture with thioglycollate-elicited rat peritoneal macrophages resulted in enhanced gelatinase production. The increase in enzyme released correlated directly with the number of macrophages added. Conditioned medium from LPS-activated peritoneal macrophages also enhanced gelatinase production in a dose-dependent manner. Fractionation of these macrophage supernatants on Sephacryl S-200 revealed a predominant fraction of gelatinase-enhancing activity in a m.w. range between 10,000 and 20,000. These data suggested that the enhanced mesangial cell gelatinase production was mediated through the action of interleukin 1. This was confirmed by the finding that purified interleukin 1, prepared from LPS-stimulated rat peritoneal macrophages, stimulated mesangial cells to secrete gelatinase in a dose-dependent manner. These findings may be of significance in the understanding of the pro-inflammatory role of macrophages in immune-mediated glomerulonephritis.

The proteins expressing interleukin 1 (IL 1) activity from rat peritoneal macrophages and cultured glomerular mesangial cells were compared after purification to apparent homogeneity. The purified IL 1 shared a number of biochemical features including m.w., charge, and specific activity. These findings were extended by the results of proteolytic peptide mapping, which revealed similar breakdown oligopeptides, confirming the close resemblance of these two IL 1 species produced by macrophages and mesangial cells. The purified mesangial cell IL 1 acts as an autocrine or paracrine growth factor. The local release of this cytokine may be an important factor in glomerular diseases characterized by mesangial proliferation and matrix expansion.