Nussler A K, Di Silvio M, Billiar T R, Hoffman R A, Geller D A, Selby R, Madariaga J, Simmons R L
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
J Exp Med. 1992 Jul 1;176(1):261-4. doi: 10.1084/jem.176.1.261.
Nitric oxide (NO) is a short-lived biologic mediator that is shown to be induced in various cell types and to cause many metabolic changes in target cells. Inhibition of tumor cell growth and antimicrobial activity has been attributed to the stimulation of the inducible type of the NO synthase (NOS). However, there is limited evidence for the existence of such inducible NOS in a human cell type. We show here the induction of NO biosynthesis in freshly isolated human hepatocytes (HC) after stimulation with interleukin 1, tumor necrosis factor (TNF), IFN-gamma, and endotoxin. Increased levels of nitrite (NO2-) and nitrate (NO3-) in culture supernatants were associated with NADPH-dependent NOS activity in the cell lysates. The production of NO2- and NO3- was inhibited by NG-monomethyl L-arginine and was associated with an increase in cyclic guanylate monophosphate release. The data presented here provide evidence for the existence of typical inducible NO biosynthesis in a human cell type.
一氧化氮（NO）是一种半衰期较短的生物介质，已证明它可在多种细胞类型中被诱导产生，并能使靶细胞发生许多代谢变化。肿瘤细胞生长的抑制和抗菌活性被归因于诱导型一氧化氮合酶（NOS）的刺激。然而，在人类细胞类型中存在这种诱导型NOS的证据有限。我们在此展示了在白细胞介素1、肿瘤坏死因子（TNF）、干扰素-γ和内毒素刺激后，新鲜分离的人肝细胞（HC）中一氧化氮生物合成的诱导情况。培养上清液中亚硝酸盐（NO2-）和硝酸盐（NO3-）水平的升高与细胞裂解物中依赖烟酰胺腺嘌呤二核苷酸磷酸（NADPH）的NOS活性相关。NO2-和NO3-的产生受到N-甲基-L-精氨酸的抑制，并与环磷酸鸟苷释放的增加相关。此处呈现的数据为人类细胞类型中典型的诱导型一氧化氮生物合成的存在提供了证据。
