Platelet-activating factor antagonist, SM-12502, attenuates experimental glomerular thrombosis in rats

Platelet-activating factor (PAF) is involved in many pathologic conditions through its potent proinflammatory and vasoactive effects. Using a specific PAF antagonist, SM-12502, we investigated the role of PAF in rat experimen tal glomerular thrombosis. In this model, sequential injections of nephroto xic serum (NTS) and lipopolysaccharide (LPS) selectively induce glomerular fibrin deposition accompanied by neutrophil accumulation. SM-12502, when in jected simultaneously with either NTS or LPS, strongly inhibited glomerular fibrin deposition in a dose-dependent manner. In contrast, neutrophil inva sion was similar in both SM-12502-injected and uninjected rats, suggesting that the antithrombotic effect was not mediated by inhibition of neutrophil migration. However, serum myeloperoxidase activity, a marker of neutrophil activation, was significantly suppressed by treatment with SM-12502. From a previous finding supporting the indispensable role of neutrophils in this model and the current observations, SM-12502 is suggested to attenuate glo merular thrombosis by inhibiting neutrophil activation. Thus, the present f indings suggest an involvement of PAF in this glomerular thrombosis model, Copyright (C) 2001 S. Karger AG, Basel.