Kröncke K D, Brenner H H, Rodriguez M L, Etzkorn K, Noack E A, Kolb H, Kolb-Bachofen V
Institute of Immunobiology, Department of Medicine, Heinrich-Heine-University of Düsseldorf, FRG.
Biochim Biophys Acta. 1993 Sep 8;1182(2):221-9. doi: 10.1016/0925-4439(93)90144-p.
To compare the sensitivity of different mammalian cell types towards the cytotoxic action of nitric oxide, freshly isolated rat pancreatic islet cells, hepatocytes, resident and activated macrophages, cultured aortic endothelial cells and two murine tumor cell lines were tested for susceptibility towards exogenous nitric oxide. As sources for nitric oxide nitroprusside, S-nitroso-N-acetyl-penicillamine and the sydnonimine-derivative SIN-1 were used. These generate nitric oxide by different mechanisms and kinetics. Among the cell types tested we found large differences in their susceptibility towards the three nitric oxide donors. Islet cells were by far the most sensitive of the investigated cells and were completely lysed by all three nitric oxide donors. Hepatocytes and endothelial cells were sensitive towards nitroprusside but relatively resistant towards toxicity of SIN-1 and S-nitroso-N-acetyl-penicillamine. Activated and resident macrophages were lysed by SIN-1, whereas high concentrations of nitroprusside and S-nitroso-N-acetyl-penicillamine led to partial cell lysis only. The tumor cell lines were both lysed by SIN-1 but showed differences in their sensitivity towards S-nitroso-N-acetyl-penicillamine. Nitric oxide, which is produced in large amounts during infection and inflammation, may play an important role in the destruction of islet cells during insulitis leading to insulin-dependent diabetes mellitus.
为比较不同哺乳动物细胞类型对一氧化氮细胞毒性作用的敏感性，对新鲜分离的大鼠胰岛细胞、肝细胞、驻留及活化巨噬细胞、培养的主动脉内皮细胞以及两种小鼠肿瘤细胞系进行了对外源性一氧化氮敏感性的测试。使用硝普钠、S-亚硝基-N-乙酰青霉胺和西多尼明衍生物SIN-1作为一氧化氮的来源。它们通过不同的机制和动力学产生一氧化氮。在所测试的细胞类型中，我们发现它们对三种一氧化氮供体的敏感性存在很大差异。胰岛细胞是所研究细胞中最敏感的，被所有三种一氧化氮供体完全裂解。肝细胞和内皮细胞对硝普钠敏感，但对SIN-1和S-亚硝基-N-乙酰青霉胺的毒性相对耐受。活化和驻留巨噬细胞被SIN-1裂解，而高浓度的硝普钠和S-亚硝基-N-乙酰青霉胺仅导致部分细胞裂解。肿瘤细胞系均被SIN-1裂解，但对S-亚硝基-N-乙酰青霉胺的敏感性存在差异。在感染和炎症期间大量产生的一氧化氮可能在胰岛炎期间胰岛细胞的破坏中起重要作用，导致胰岛素依赖型糖尿病。
