INCREASE PRODUCTION OF FIBRONECTIN BY GLOMERULAR CULTURES FROM RATS WITH NEPHROTOXIC NEPHRITIS - MACROPHAGES INDUCE FIBRONECTIN PRODUCTION IN CULTURED MESANGIAL CELLS

BACKGROUND: The participation of monocytes-macrophages and their produ cts in the pathogenesis of several types of glomerulonephritis has bec ome increasingly evident. One of the most important aspects is the pot ential stimulation of monocyte-macrophages of the extracellular matrix . Therefore, production of fibronectin (FN) by glomeruli of rats with nephrotoxic nephritis was studied. In addition, the effect of macropha ge-conditioned medium and interleukin-1 on FN production by cultured m esangial cell (MC) was tested. EXPERIMENTAL DESIGN: Nephrotoxic nephri tis was induced in rats by injection of nephrotoxic serum and glomerul i obtained at different periods of time from nephritic and normal anim als were cultured. FN in glomerular supernatants was determined by enz yme-linked immunosorbent assay and newly synthesized FN by incorporati on of [S-35]-methionine. Macrophage-conditioned medium was obtained fr om cultures of peritoneal resident macrophages and elicited macrophage s by different stimuli. MC were cultured with or without macrophage su pernatant or interleukin-1 and FN content from MC supernatants was det ermined by enzyme-linked immunosorbent assay. RESULTS: These data show increase amounts of FN in nephritic cultures when compared with salin e controls (time of nephritis; day 4: 3.9-, day 8: 4.35-, and day 18: 2.68-fold increase in FN) and experiments of newly synthesized FN by i ncorporation of [S-35]-methionine had similar results. Macrophage-cond itioned medium had FN stimulatory effect on cultured MC but interleuki n-1 did not. CONCLUSIONS: These data suggest: (a) that there is an inc reased newly synthesized FN production in glomeruli from rats with nep hrotoxic nephritis, (b) that macrophage produce a FN-stimulatory facto r(s) for MC, and (c) that this stimulatory factor probably is not inte rleukin-1.