Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes.
Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes.
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发表时间：
1986
期刊：
影响因子：
6.4
通讯作者：
G. Rook;J. Steele;L. Fraher;S. Barker;R. Karmali;J. O'riordan;J. Stanford
中科院分区：
文献类型：
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作者：
G. Rook;J. Steele;L. Fraher;S. Barker;R. Karmali;J. O'riordan;J. Stanford
先前的研究表明，重组干扰素γ (ifn - γ)、粗T细胞上清液或合适的T细胞系可以完全抑制小鼠腹膜巨噬细胞内结核分枝杆菌的生长。在人类单核细胞的类似实验中，观察到的影响要小得多。这可能是由于这些细胞相对不成熟。由于二羟基维生素D3 （1,25-(OH)2 D3）可以导致未成熟白血病细胞系表型分化为巨噬细胞样细胞，我们已经探索了在体外暴露于胆钙化醇代谢物可能会增加单核细胞控制结核分枝杆菌增殖的能力，或导致单核细胞成熟为能够对ifn - γ作出适当反应的细胞的可能性。具有三种胆骨化醇代谢物的单核细胞孵育诱导抗结核活性，其程度与它们与衍生物的细胞内受体蛋白的结合亲和力相关。1,25-(OH)2 D3还为磷酸肉豆蔻酸酯引发的硝基蓝四氮唑还原启动单核细胞。与ifn - γ的作用是相加性的，而不是协同性的。与ifn - γ孵育的单核细胞产生25-OH D3 1-羟化酶活性，通过将氚化的25-(OH) D3转化为更极性的代谢物，在正相和反相HPLC上与1,25-(OH)2 D3共洗脱来检测。后者在体内更为活跃。这些发现有助于解释维生素D在治疗某些形式结核病方面的功效，以及偶尔发现这些患者血清钙升高和维生素D代谢紊乱。
Previous studies have shown that recombinant interferon gamma (IFN-gamma), crude T cell supernatants, or appropriate T-cell lines can cause total inhibition of the growth of M. tuberculosis inside murine peritoneal macrophages. In similar experiments with human monocytes much smaller effects are seen. This could be due to the relative immaturity of these cells. Because dihydroxy vitamin D3 (1,25-(OH)2 D3) can cause phenotypic differentiation of immature leukemic lines into macrophage-like cells, we have explored the possibility that exposure to cholecalciferol metabolites in vitro might increase the ability of monocytes to control proliferation of M. tuberculosis, or cause monocytes to mature into cells able to respond appropriately to IFN-gamma. Incubation of monocytes with three cholecalciferol metabolites induced anti-tuberculosis activity to an extent that correlated with their binding affinities to the intracellular receptor protein for the derivatives. 1,25-(OH)2 D3 also primed monocytes for phorbol myristate acetate-triggered reduction of nitroblue tetrazolium. The effects were additive rather than synergistic with those of IFN-gamma. Monocytes incubated with IFN-gamma developed 25-OH D3 1-hydroxylase activity, detected by conversion of tritiated 25-(OH) D3 to a more polar metabolite which coeluted with 1,25-(OH)2 D3 on straight and reverse-phase HPLC. The latter is a more active form in vivo. These findings help to explain claims for the efficacy of vitamin D in the treatment of some forms of tuberculosis, and also the occasional finding of raised serum calcium, and disturbed vitamin D metabolism in these patients.