Proliferative glomerulonephritis in rats: evidence that mononuclear phagocytes infiltrating the glomeruli stimulate the proliferation of endothelial and mesangial cells.

A proliferative, non-crescentic, glomerulonephritis (GN) was induced in rats preimmunized with rabbit IgG by injecting a sub-nephrotoxic dose of rabbit anti-GMA IgG. Control rats either received anti-GBM IgG only, or were totally irradiated (800 rads, kidneys protected) 2 days before the second injection. All the GN rats developed a severe proteinuria within 2-4 days after the injection of anti-GBM IgG, contrarily to the control rats. At the same time, many mononuclear cells, of predominantly extra-renal origin, infiltrated the glomeruli. Glomeruli were isolated from GN, normal and control rats and were cultivated in RPMI medium. In normal and control rats cultures, epithelial and mesangial cells were observed. In GN rat cultures, not only epithelial and mesangial cells, but also endothelial and macrophagic cells were identified; the outgrowth capacity of the mesangial cells was enhanced. These data were particularly evident in cultures of GN glomeruli isolated within 2-4 days after the induction of the renal disease, exactly when the glomeruli were infiltrated by a large number of mononuclear phagocytes. It is suggested that the mononuclear phagocytes infiltrating the glomeruli of rats with this model of GN stimulate the proliferation of endothelial and mesangial cells in vitro.