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 experimental glomerular thrombosis. In this model, sequential injections of nephrotoxic serum (NTS) and lipopolysaccharide (LPS) selectively induce glomerular fibrin deposition accompanied by neutrophil accumulation. SM-12502, when injected simultaneously with either NTS or LPS, strongly inhibited glomerular fibrin deposition in a dose-dependent manner. In contrast, neutrophil invasion 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 glomerular thrombosis by inhibiting neutrophil activation. Thus, the present findings suggest an involvement of PAF in this glomerular thrombosis model.