Abstract
When a streptococcal preparation OK-432 was intraperitoneally injected for the treatment of carcinomatous peritonitis, antitumor PMN accumulated in the peritoneal cavity. Increases of C5a, thromboxane B2 and leukotriene B4 were observed before the accumulation of PMN in ascitic fluid. Here, we examined mechanism of this PMN accumulation using an in vivo system in rats employing anticomplementary reagents and proteinase inhibitors. FUT-175, EDTA and K 76 inhibited C5a generation by OK-432 in vitro, but EGTA, FOY and urinastatin did not. In in vivo experiments, EDTA, FUT-175, anti-rat C3 serum, K 76, FOY and urinastatin reduced the accumulation of PMN onto filter membranes, when these reagents were reacted with OK-432 for 3hrs through filter membranes placed on the turned peritoneum in rats. EGTA did not inhibit PMN accumulation. This inhibition of PMN accumulation were confirmed by histological examination. It is suggested that complement-derived chemotactic factor C5a generated by OK-432 induces PMN accumulation in association with clotting, fibrinolytic and kinin systems.
