[Extracapillary glomerulonephritis with fibrin deposits. Role of thrombin]

Fibrin deposits are frequent in experimental and human glomerulonephritides. In rapidly progressive glomerulonephritis (RPGN), fibrin deposits are considered as a factor generating glomerular sclerosis leading to renal failure. In RPGN, proliferation of epithelial cells associated with macrophages and fibrin deposits is observed in Bowman's space. It is known that 1) thrombin may be locally generated by tissue factor from glomerular cells and macrophages, 2) active thrombin may be adsorbed into the plug. Using immortalized human glomerular epithelial cells, we have tested the hypothesis that active thrombin may be a potential mediator of cellular proliferation, fibrin deposits persistency and collagen IV synthesis. The results clearly demonstrate that epithelial cells bind specifically iodinated alpha-thrombin. Thereafter, these cells synthesize specific inhibitors of plasminogen activators, converting their fibrinolytic activity into antifibrinolytic activity. Moreover, they synthesize soluble form of type IV collagen. A new therapeutical approach of RPGN may be taken into account based on the ability of new drugs inhibiting the binding of thrombin on its specific receptors, and/or inhibiting the extrinsic pathway of the fibrin formation.