Effect of fibrin matrix on growth of glomerular cells

Rat glomerular cells were grown either in or on fibrin clots prepared from rat plasma to assess the effect of native fibrin on the growth of glomerular epithelial and mesangial cells. Progressive fibrinolysis was observed in glomerular explant cultures without epsilon-aminocaproic acid (EACA), an inhibitor of plasminogen activation. The lytic areas extended as the cell number of glomerular explant outgrowths increased. Glomerular cultures containing 0.5% EACA showed complete inhibition of fibrinolysis. Under this condition, the glomerular outgrowths developed only when the glomerular explants were seeded on the surface of fibrin matrix. While the explants were embedded in the fibrin matrix, few cells could grow out of explants. The more prosperous growth of glomerular epithelial cells in the lytic areas and the lack of intimate binding of glomerular epithelial cell membrane with fibrin fibers implied that fibrin might hinder the outgrowth of glomerular epithelial cells. The mesangial cells, whether growing on the surface of or embedded in the fibrin matrix, showed no fibrinolytic activity. Inhibition of fibrinolysis did not alter the growth pattern of mesangial cells. In addition, mesangial cells exhibited extensive binding of fibrin fibers on their cell surface and developed conspicuous arborization of their cell processes. These features suggested a close affinity between mesangial cells and fibrin matrix. These experiments have addressed our attention to the particular roles of the visceral epithelial cells and mesangial cells in the pathogenesis of fibrin-related glomerulonephritis.