Schneemann M, Schoedon G, Hofer S, Blau N, Guerrero L, Schaffner A
Department of Medicine, University of Zurich Medical School, Switzerland.
J Infect Dis. 1993 Jun;167(6):1358-63. doi: 10.1093/infdis/167.6.1358.
Nitric oxide synthase (NOS) has received immense interest as an antimicrobial and antitumoral effector system of mononuclear phagocytes from rodents. Because there is increasing doubt that an analogous system exists in human macrophages, NOS was reexamined in these cells. Under tightly controlled conditions, with murine macrophages as positive controls, human macrophages failed to secrete nitric oxide (< 0.1 mumol/10(6) cells/24 h), even after activation with endotoxin, interferon-gamma, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, bacteria, or proliferating lymphocytes. The discrepancy between murine and human macrophages depended on neither the anatomic source (blood, peritoneum), the agent used for activation, nor the duration of activation. NOS activity was paralleled by metabolization of L-arginine to L-citrulline. Exogenous tetrahydrobiopterin, an essential cofactor of NOS not synthesized by human macrophages, did not support NOS activity in human macrophages. Also, no NOS activity was found in cellular subfractions of human macrophages. It appears that in humans, the inducible high-output NOS is not conserved as an antimicrobial system of macrophages.
一氧化氮合酶（NOS）作为啮齿动物单核吞噬细胞的一种抗菌和抗肿瘤效应系统，已引起了广泛关注。由于越来越多的人怀疑人类巨噬细胞中是否存在类似的系统，因此对这些细胞中的NOS进行了重新研究。在严格控制的条件下，以鼠巨噬细胞作为阳性对照，即使在用内毒素、干扰素-γ、粒细胞-巨噬细胞集落刺激因子、肿瘤坏死因子-α、细菌或增殖淋巴细胞激活后，人类巨噬细胞也未能分泌一氧化氮（<0.1 μmol/10⁶ 细胞/24小时）。鼠巨噬细胞和人类巨噬细胞之间的差异既不取决于解剖学来源（血液、腹膜），也不取决于用于激活的试剂或激活的持续时间。NOS活性与L-精氨酸代谢为L-瓜氨酸的过程平行。外源性四氢生物蝶呤是一种人类巨噬细胞无法合成的NOS必需辅因子，它不能支持人类巨噬细胞中的NOS活性。此外，在人类巨噬细胞的细胞亚组分中未发现NOS活性。看来在人类中，诱导型高产量NOS作为巨噬细胞的抗菌系统并未保留下来。
