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 evaluated the fibrinolytic activity of glomeruli isolated from rabbits infused for 5 h with tumor necrosis factor (TNF) at the doses of 0.8 micrograms/kg/h (n = 5) and 8 micrograms/kg/h (n = 3) or with endotoxin (8 micrograms/kg/h, n = 7). Animals infused with vehicle (n = 11) served as control group. Plasminogen activator (PA) activity of glomerular extracts from rabbits infused with 8 micrograms/kg/h of TNF or endotoxin was significantly lower than that of samples from control animals (p = 0.013 and p = 0.003, respectively). At the dose of 0.8 micrograms/kg/h, TNF caused a reduction in glomerular PA activity which, however, did not reach statistical significance. Neither plasminogen-independent activity nor PA inhibitor activity was detected in glomerular extracts. Fibrin autography of control extracts revealed the presence of two main fibrinolytic activities comigrating with purified urokinase-type and tissue-type PAs. In treated samples, the bands corresponding to free PAs were markedly reduced, with no evidence of enzyme-inhibitor complex formation. Local reduction of fibrinolytic capacity may contribute to intraglomerular fibrin deposition during endotoxemia or in renal inflammatory diseases associated with TNF production.