Glomerular cells and macrophages in the progression of experimental focal and segmental glomerulosclerosis

To determine the characteristics of glomerular cell involvement in experimental focal and segmental glomerulosclerosis (FGS) in rats induced by repeated injections of aminonucleoside of puromycin (PAN) and protamine sulfate (PS), glomeruli were isolated and grown in tissue culture. When compared with saline controls the FGS rats had decreased rates of glomerular attachment and significantly reduced outgrowths of type 1 (epithelial) and type II (mesangial) cells. However, the FGS rats had greater numbers of type III cells (macrophages) present in the outgrowths than controls. The production of interleukin-1 (IL-1) in the glomerular culture supernatant, measured by thymocyte stimulating activity, was determined at various stages throughout the evolution of FGS and in saline controls. The FGS glomeruli early in the disease course (day 10) had higher levels of IL-1 activity than glomerular outgrowths from control rats but significantly lower levels of IL-1 were produced late in the disease (day 80). Glomerular macrophages were present throughout the evolution of the disease but in greater numbers early (day 10). In this experimental model of FGS, IL-1 production, has been demonstrated early in the disease process, could originate from macrophages and/or mesangial cells, and could be involved in the progressive glomerulosclerosis.