Enhancement of glomerular mesangial cell neutral proteinase secretion by macrophages: role of interleukin 1.

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.