Morin C, Fessi H, Devissaguet J P, Puisieux F, Barratt G
Laboratoire de Pharmacotechnie-Biopharmacie, URA CNRS 1218, Université de Paris Sud, Faculté de Pharmacie, Châtenay-Malabry, France.
Biochim Biophys Acta. 1994 Dec 30;1224(3):427-32. doi: 10.1016/0167-4889(94)90278-x.
Treatment with muramyldipeptide (MDP) or a lipophilic derivative (MTP-Chol) included in nanocapsules renders macrophages cytostatic towards tumor cells. At the same time, nitric oxide (NO) synthase (EC 1.14.23) activity is induced, as determined by measurement of the two end products of the reaction (nitrite and L-citrulline). The objective of this study was to investigate some factors which might influence this activation and explain the decreased response observed at high nanocapsule concentrations. The glucose content of the medium did not seem to be limiting. Addition of indomethacin decreased nitrite production in the effector phase, suggesting a role for prostaglandins in the maintenance of the activated state. We also tested the hypothesis that NO itself might regulate inducible nitric oxide synthase activity. The addition of NO donors (SIN-1 and nitrosoglutathione) or superoxide dismutase to cultures of activated macrophages inhibited the NO synthase activity. Since these NO donors were non toxic towards macrophages, these observations indicate clearly that the addition of exogenous NO to that formed by the enzymatic reaction can cause inhibition of the inducible NO synthase.
用包含在纳米胶囊中的胞壁酰二肽（MDP）或亲脂性衍生物（MTP - Chol）进行处理，可使巨噬细胞对肿瘤细胞产生细胞抑制作用。同时，通过测量反应的两种终产物（亚硝酸盐和L - 瓜氨酸）确定，一氧化氮（NO）合酶（EC 1.14.23）活性被诱导。本研究的目的是调查一些可能影响这种激活的因素，并解释在高纳米胶囊浓度下观察到的反应降低现象。培养基中的葡萄糖含量似乎不是限制因素。添加吲哚美辛会降低效应阶段的亚硝酸盐产生，这表明前列腺素在维持激活状态中起作用。我们还测试了NO本身可能调节诱导型一氧化氮合酶活性的假设。向活化巨噬细胞培养物中添加NO供体（SIN - 1和亚硝基谷胱甘肽）或超氧化物歧化酶会抑制NO合酶活性。由于这些NO供体对巨噬细胞无毒，这些观察结果清楚地表明，向酶促反应形成的NO中添加外源性NO可导致诱导型NO合酶的抑制。
