Zembala M, Siedlar M, Marcinkiewicz J, Pryjma J
Department of Clinical Immunology, PA IP, Jagiellonian University Medical College, Cracow, Poland.
Eur J Immunol. 1994 Feb;24(2):435-9. doi: 10.1002/eji.1830240225.
Nitric oxide (NO) has been recently identified as a potent mediator of tumoricidal activity of activated macrophages. Macrophages can be activated for tumor cell killing by microbial products, including lipopolysaccharide (LPS) and various cytokines. Here we report that in contrast to mouse macrophages, human peripheral blood monocytes stimulated with cytokines or LPS failed to release NO. Also priming of monocytes with interferon-gamma followed by activation with cytokines or LPS did not cause NO secretion. However, monocytes responded with NO production to stimulation with some human cancer cells but not with untransformed cells. NO production by monocytes was inhibited by NG-monomethyl-L-arginine, specific inhibitor of NO synthase and emetine, an irreversible blocker of protein synthesis. This may imply that human monocytes are unique in their restricted capacity to produce NO following interaction with some tumor cells, but not with other stimulators, and in this respect they may be able to distinguish between malignant and normal cells.
一氧化氮(NO)最近被确认为活化巨噬细胞杀瘤活性的一种强效介质。巨噬细胞可被包括脂多糖(LPS)和各种细胞因子在内的微生物产物激活,从而杀伤肿瘤细胞。在此我们报告,与小鼠巨噬细胞不同,用细胞因子或LPS刺激的人外周血单核细胞未能释放NO。先用γ干扰素预处理单核细胞,然后再用细胞因子或LPS激活,也不会导致NO分泌。然而,单核细胞对某些人癌细胞的刺激会产生NO,而对未转化细胞的刺激则无此反应。单核细胞产生NO受到NO合酶的特异性抑制剂NG-单甲基-L-精氨酸和蛋白质合成的不可逆阻断剂吐根碱的抑制。这可能意味着,人单核细胞在与某些肿瘤细胞而非其他刺激物相互作用后产生NO的能力有限,具有独特性,在这方面它们可能能够区分恶性细胞和正常细胞。