Ivanova K, Le Poole I C, Gerzer R, Westerhof W, Das P K
German Aerospace Research Establishment, Institute of Aerospace Medicine, Cologne, Germany.
J Pathol. 1997 Dec;183(4):469-76. doi: 10.1002/(SICI)1096-9896(199712)183:4<469::AID-PATH931>3.0.CO;2-T.
The aim of the present study was to explore whether nitric oxide (NO) interferes with the attachment of human melanocytes to the extracellular matrix (ECM) components. Consequently, the effects have been investigated of the NO-releasing compounds 3-morpholino-sydnonimine (SIN-1) and S-nitroso-glutathione (GSNO) on the in vitro adhesion of human melanocytic cells to fibronectin. The NO donors induced a concentration-dependent reduction in the adhesion of both 51CrO4(2-)-labelled melanocytes and melanoma cells to fibronectin. Pigmented M14 melanoma cells were more susceptible to the effect of SIN-1 (half-maximal inhibiting effect at about 0.5 mM) than normal human melanocytes and also than the non-pigmented melanoma cells Mel57 (half-maximal inhibiting effects between 0.9 and 2 mM). This effect of SIN-1 also appeared to be related to the melanin content of normal melanocytes, whereas GSNO was significantly less active. Both flow cytometric analysis and immunocytochemical staining showed expression of neuronal NO synthase in all cell lines. The results of this study suggest that aberrant in vivo production of NO during infection and inflammation may contribute to loss of melanocytes in, for example, vitiligo, by reducing de novo attachment of melanocytes to the ECM. These findings could also be important for understanding the process of metastasis.
本研究的目的是探讨一氧化氮（NO）是否会干扰人黑素细胞与细胞外基质（ECM）成分的附着。因此，研究了释放NO的化合物3-吗啉代-西多胺（SIN-1）和S-亚硝基谷胱甘肽（GSNO）对人黑素细胞体外黏附于纤连蛋白的影响。NO供体使51CrO4(2-)标记的黑素细胞和黑素瘤细胞与纤连蛋白的黏附呈浓度依赖性降低。色素沉着的M14黑素瘤细胞比正常人黑素细胞以及非色素沉着的黑素瘤细胞Mel57对SIN-1的作用更敏感（半最大抑制效应约为0.5 mM），Mel57的半最大抑制效应在0.9至2 mM之间。SIN-1的这种作用似乎也与正常黑素细胞的黑色素含量有关，而GSNO的活性明显较低。流式细胞术分析和免疫细胞化学染色均显示所有细胞系中均有神经元型一氧化氮合酶表达。本研究结果表明，感染和炎症期间体内异常产生的NO可能通过减少黑素细胞重新附着于ECM，导致例如白癜风中黑素细胞的丧失。这些发现对于理解转移过程也可能很重要。
