Filley E A, Bull H A, Dowd P M, Rook G A
Department of Medical Microbiology, University College, London, U.K.
Immunology. 1992 Dec;77(4):505-9.
It has previously been shown that the inherently tumour necrosis factor-alpha (TNF-alpha)-sensitive L929 murine fibroblast cell line becomes much more sensitive to the cytotoxic effect of this cytokine after exposure to Mycobacterium tuberculosis in culture. In this study it is now shown that normal human cells of types likely to be involved in tuberculous lesions are affected in a similar way. Growth of normal human fibroblasts is usually stimulated by TNF-alpha in vitro, but after exposure to M. tuberculosis or to extracts of this organism, these cells are killed rather than stimulated by subsequent exposure to TNF-alpha. Similarly, human endothelial cells become susceptible to doses to TNF-alpha which do not normally affect viability. Moreover this enhancement of sensitivity to TNF-alpha is not confined to its toxicity. Endothelial cells and HeLa cells exposed to M. tuberculosis express increased levels of ICAM-1 after subsequent exposure to TNF-alpha, implying synergy between the two stimuli. It is suggested that these effects contribute to the ability of M. tuberculosis to distort the normal protective role of TNF-alpha so that the cytokine becomes detrimental to the host.
先前已经表明，在培养中暴露于结核分枝杆菌后，固有地对肿瘤坏死因子-α（TNF-α）敏感的L929小鼠成纤维细胞系对这种细胞因子的细胞毒性作用变得更加敏感。在本研究中，现已表明，可能参与结核病变的正常人类细胞也受到类似影响。正常人类成纤维细胞的生长在体外通常受到TNF-α的刺激，但在暴露于结核分枝杆菌或该生物体的提取物后，这些细胞在随后暴露于TNF-α时被杀死而不是受到刺激。同样，人内皮细胞对通常不影响活力的TNF-α剂量变得敏感。此外，对TNF-α敏感性的这种增强不仅限于其毒性。暴露于结核分枝杆菌的内皮细胞和HeLa细胞在随后暴露于TNF-α后表达增加水平的细胞间黏附分子-1（ICAM-1），这意味着两种刺激之间存在协同作用。有人提出，这些效应有助于结核分枝杆菌扭曲TNF-α的正常保护作用，从而使细胞因子对宿主有害。
