Sarih M, Souvannavong V, Adam A
CNRS-URA 1116, Institut de Biochimie, Université Paris-Sud, Orsay, France.
Biochem Biophys Res Commun. 1993 Mar 15;191(2):503-8. doi: 10.1006/bbrc.1993.1246.
Stimulation processes effective for macrophage (M phi) cytostasis induction also led to a L-arginine-dependent M phi cell death by apoptosis in parallel to nitrite and citrulline production. Resident M phi stimulated with LPS plus IFN-gamma and MDP produced high amounts of nitrite and underwent apoptosis. Inflammatory M phi treated with LPS or IFN-gamma alone produced low levels of nitrite and were not apoptotic, whereas a synergistic effect was observed, the combined treatment leading to high amounts of nitrite and to apoptosis. Primed M phi obtained from concanavalin A-treated mice, after stimulation with LPS alone, released high amounts of nitrite and exhibited the typical ladder pattern of DNA fragmentation of apoptotic cells. In the three cases the L-arginine-dependent nitrite production was inhibited by NG-monomethyl-L-arginine, a competitive inhibitor of NO synthase, which moreover, also inhibited cell apoptosis. These findings and kinetics studies suggest the involvement of NO synthase in apoptosis induction.
对巨噬细胞（M phi）细胞生长抑制诱导有效的刺激过程，同时也通过凋亡导致了依赖L-精氨酸的M phi细胞死亡，这与亚硝酸盐和瓜氨酸的产生并行。用脂多糖（LPS）加γ干扰素（IFN-γ）和胞壁酰二肽（MDP）刺激的驻留M phi产生大量亚硝酸盐并发生凋亡。单独用LPS或IFN-γ处理的炎性M phi产生低水平的亚硝酸盐且不发生凋亡，而观察到协同效应，联合处理导致大量亚硝酸盐产生并引发凋亡。从刀豆球蛋白A处理的小鼠获得的致敏M phi，在用LPS单独刺激后，释放大量亚硝酸盐并呈现凋亡细胞典型的DNA片段梯形条带模式。在这三种情况下，一氧化氮合酶的竞争性抑制剂N G-单甲基-L-精氨酸抑制了依赖L-精氨酸的亚硝酸盐产生，而且还抑制了细胞凋亡。这些发现和动力学研究提示一氧化氮合酶参与凋亡诱导。
