Differential sensitivity of C57BL/6 (M-1) and BALB/c (M-2) macrophages to the stimuli of IFN-γ/LPS for the production of NO:: Correlation with iNOS mRNA and protein expression
Differential sensitivity of C57BL/6 (M-1) and BALB/c (M-2) macrophages to the stimuli of IFN-γ/LPS for the production of NO:: Correlation with iNOS mRNA and protein expression
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DOI：
10.1089/jir.2006.26.682
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发表时间：
2006-09-01
影响因子：
2.3
通讯作者：
Horta, M. Fatima
中科院分区：
文献类型：
--
作者：
Santos, Jane L.;Andrade, Anderson A.;Horta, M. Fatima
C57BL/6和BALB/c小鼠是研究几种传染病抵抗力和易感性的原型宿主。在许多情况下，C57BL/6的耐药性是由于巨噬细胞产生的一氧化氮(NO)对主要由Th1细胞和巨噬细胞分别分泌的干扰素-γ(干扰素-γ)和肿瘤坏死因子-α(肿瘤坏死因子-α)产生的杀菌作用。BALB/c通常不能产生Th1淋巴细胞，不能控制某些感染。然而，我们和其他人之前已经观察到，无论适应性免疫反应如何，C57BL/6(M-1)巨噬细胞比BALB/c(M-2)细胞对干扰素-γ加脂多糖(LPS)刺激产生NO更敏感，这一特征也可能是耐药的原因。在这里，我们报道了M-1和M-2巨噬细胞产生NO的差异与诱导型一氧化氮合酶(INOS)mRNA和蛋白的积累有关，这表明iNOS在M-1和M-2细胞中的表达是不同的调节。诱导型一氧化氮合酶基因在M-1细胞中的高积聚与其稳定性无关，因此，在这些细胞中iNOS基因的转录可能比在M-2细胞中更有效。一个值得注意的发现是M-1巨噬细胞的iNOS蛋白水平远高于M-2细胞，这使我们推测iNOS基因的差异翻译或翻译后调控是有效的。
C57BL/6 and BALB/c mice are prototype hosts for the study of resistance and susceptibility to several infectious diseases. In many cases, resistance of C57BL/6 is due to the microbicidal effect of nitric oxide (NO) produced by macrophages in response to interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), mainly secreted by Th1 cells and macrophages, respectively. BALB/c, usually unable to give rise to Th1 lymphocytes, does not control certain infections. However, we and others have previously observed that regardless of the adaptive immune response, C57BL/6 (M-1) macrophages are far more sensitive to the stimulus of IFN-gamma-plus lipopolysaccharide (LPS) for the production of NO than are BALB/c (M-2) cells, a feature that might also account for resistance. Here, we report that the differential production of NO by M-1 and M-2 macrophages correlates with the accumulation of inducible nitric oxide synthase (iNOS) mRNA and protein, which shows that expression of iNOS is differentially regulated in M-1 and M-2 cells. The higher accumulation of iNOS mRNA in M-1 cells is independent of its stability, and, thus, it is possible that transcription of the iNOS gene in these cells may be more efficient than in M-2 cells. A remarkable finding is that the level of iNOS protein is much higher in M-1 macrophages than in M-2 cells, as compared with the mRNA levels, which makes us speculate that differential translational or posttranslational controls of iNOS gene are operative.