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骨髓来源巨噬细胞分化过程中MHC基因表达的调控

Regulation of MHC gene expression during the differentiation of bone marrow-derived macrophages.

作者信息

Pullen J K, Eustis-Turf E, Myers M J, Schook L B

机构信息

Department of Microbiology and Immunology, Medical College of Virginia, Richmond 23284.

出版信息

Cell Immunol. 1989 Jul;121(2):398-413. doi: 10.1016/0008-8749(89)90039-7.

DOI:10.1016/0008-8749(89)90039-7
PMID:2500255
Abstract

The ability of the macrophage to express class II MHC gene products appears to arise from both T-dependent and T-independent mechanisms. One mechanism by which macrophages express Ia-antigens in the absence of T-lymphocytes is postulated to be controlled by differentiation. By using a liquid bone marrow culture system, we have studied both class I and class II surface expression and mRNA accumulation during macrophage differentiation in vitro. The results demonstrated that Ia expression increased until 7 days in culture and then slowly declined. In contrast, class I expression appeared to steadily increase throughout the differentiation period. Northern blot analysis of RNA isolated from bone marrow-derived macrophages (BMDM) at various periods during culture, using E alpha, A alpha, and class I cDNA probes, correlated well with the results of Ia and H-2K surface expression. Further analysis demonstrated that the expression of Ia-antigens on BMDM was not the result of T-helper lymphocytes. This was determined by demonstrating (1) that bone marrow cultures were devoid of mature T-lymphocytes, (2) the absence of interferon (IFN)-gamma transcripts in both adherent and nonadherent populations of bone marrow cells, and (3) that the addition of anti-IFN-gamma monoclonal antibody (mAb) to the bone cultures did not alter the percentage of Ia-positive BMDM. Moreover, the addition of anti-tumor necrosis factor-alpha mAb to the bone marrow cultures had no effect on Ia expression by BMDM. Taken together, these results allow us to conclude that Ia expression by BMDM is probably not mediated via exogenous signals but rather results from an intrinsically controlled process.

摘要

巨噬细胞表达II类主要组织相容性复合体(MHC)基因产物的能力似乎源于T细胞依赖性和T细胞非依赖性机制。巨噬细胞在无T淋巴细胞的情况下表达Ia抗原的一种机制被认为受分化控制。通过使用液体骨髓培养系统,我们研究了体外巨噬细胞分化过程中I类和II类表面表达以及mRNA积累情况。结果表明,Ia表达在培养7天前增加,然后缓慢下降。相比之下,I类表达在整个分化期似乎持续增加。使用Eα、Aα和I类cDNA探针,对培养不同时期从骨髓来源的巨噬细胞(BMDM)中分离的RNA进行Northern印迹分析,结果与Ia和H-2K表面表达的结果高度相关。进一步分析表明,BMDM上Ia抗原的表达不是T辅助淋巴细胞作用的结果。这是通过以下几点确定的:(1)骨髓培养物中没有成熟的T淋巴细胞;(2)骨髓细胞的贴壁和非贴壁群体中均不存在干扰素(IFN)-γ转录本;(3)向骨髓培养物中添加抗IFN-γ单克隆抗体(mAb)不会改变Ia阳性BMDM的百分比。此外,向骨髓培养物中添加抗肿瘤坏死因子-α mAb对BMDM的Ia表达没有影响。综上所述,这些结果使我们得出结论,BMDM的Ia表达可能不是通过外源性信号介导的,而是由内在控制的过程导致的。

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