Watanabe M, Shishido Y, Hirasawa N, Mue S, Fujiki H, Ohuchi K
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
Biochim Biophys Acta. 1992 Feb 14;1138(2):157-61. doi: 10.1016/0925-4439(92)90056-s.
A streptococcal preparation OK-432 is reported to be an immunopotentiator and a potent antitumor agent. In order to elucidate the mechanism of biologic action, effects of OK-432 on arachidonic acid metabolism in rat peritoneal macrophages were investigated. Prostaglandin E2 production and release of radioactivity from [3H]arachidonic acid-labeled macrophages were found to be stimulated by OK-432 in a concentration-dependent manner (5 to 80 micrograms/ml). Heat-treatment of OK-432 further stimulated its effects. These stimulative effects on arachidonic acid metabolism by OK-432 were not observed in MDCK cells that have no phagocytotic activity. Furthermore, cytochalasin B treatment completely suppressed the stimulative effects induced by OK-432 in macrophages. These results strongly indicate that the stimulative effects by OK-432 on arachidonic acid metabolism are dependent on phagocytosis of OK-432 particles. Significance of stimulation of arachidonic acid metabolism in macrophages by OK-432 for its biological effects is discussed.
据报道,链球菌制剂OK-432是一种免疫增强剂和强效抗肿瘤剂。为了阐明其生物作用机制,研究了OK-432对大鼠腹腔巨噬细胞花生四烯酸代谢的影响。发现OK-432以浓度依赖性方式(5至80微克/毫升)刺激[3H]花生四烯酸标记的巨噬细胞产生前列腺素E2并释放放射性。OK-432的热处理进一步增强了其作用效果。在没有吞噬活性的MDCK细胞中未观察到OK-432对花生四烯酸代谢的这些刺激作用。此外,细胞松弛素B处理完全抑制了OK-432在巨噬细胞中诱导的刺激作用。这些结果强烈表明,OK-432对花生四烯酸代谢的刺激作用取决于OK-432颗粒的吞噬作用。讨论了OK-432刺激巨噬细胞花生四烯酸代谢对其生物学效应的意义。