REDUCED FIBRINOLYTIC-ACTIVITY IN GLOMERULI ISOLATED FROM RABBITS INFUSED WITH TUMOR-NECROSIS-FACTOR

Glomerular fibrin deposition may result from local activation of blood coagulation and/or impaired removal by the fibrinolytic system. We ev aluated the fibrinolytic activity of glomeruli isolated from rabbits i nfused for 5 h with tumor necrosis factor (TNF) at the doses of 0. 8 m ug/kg/h (n = 5) and 8 mug/kg/h (n = 3) or with endotoxin (8 mug/kg/h, n = 7). Animals infused with vehicle (n = 11) served as control group. Plasminogen activator (PA) activity of glomerular extracts from rabbi ts infused with 8 mug/kg/h of TNF or endotoxin was significantly lower than that of samples from control animals (p = 0.013 and p = 0.003, r espectively). At the dose of 0.8 mug/kg/h, TNF caused a reduction in g lomerular PA activity which, however, did not reach statistical signif icance. Neither plasminogen-independent activity nor PA inhibitor acti vity was detected in glomerular extracts. Fibrin autography of control extracts revealed the presence of two main fibrinolytic activities co migrating with purified urokinase-type and tissue-type PAs. In treated samples, the bands corresponding to free PAs were markedly reduced, w ith no evidence of enzyme-inhibitor complex formation. Local reduction of fibrinolytic capacity may contribute to intraglomerular fibrin dep osition during endotoxemia or in renal inflammatory diseases associate d with TNF production.