Cytokine modulatable signalling through macrophage HLA class II. 1. IFN-gamma upregulates the efficiency of Ca2+ mobilization in response to ligation of macrophage HLA-DP.
Cytokine modulatable signalling through macrophage HLA class II. 1. IFN-gamma upregulates the efficiency of Ca2+ mobilization in response to ligation of macrophage HLA-DP.
复制标题
通过巨噬细胞 HLA II 类的细胞因子可调节信号传导。
DOI：
10.1089/jir.1997.17.671
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Yu,J
中科院分区：
文献类型：
--
作者：
Dialynas,DP;Tan,PC;Yu,J
最近从外周血中建立的人巨噬细胞系2MAC表达许多谱系特异性标记和广泛的细胞间黏附分子，包括高水平的HLAI和II类。我们在其他地方提出证据表明2MAC可以有效地应用于巨噬细胞通过HLAII类的信号转导的研究。也就是说，我们证明了单抗与2MAC的HLAII类结合，而不是HLAI类结合，可以引起细胞内游离钙离子浓度[Ca2+]i的增加。此外，这种钙离子流量似乎与功能相关：连接HLADR，而不是HLAI类，单抗导致依赖于钙离子动员的组织因子的诱导，组织因子是凝血因子VII/VIIa的高亲和力细胞受体。在这里，我们证明了2MAC对于解决通过HLAII类的信号转导的效率是唯一有价值的。也就是说，我们在这里展示了预先培养的2MAC细胞与干扰素-γ(干扰素-γ)一起培养后，在没有增加细胞表面HLADP表达的情况下，对连接HLADP的反应，深刻地上调了随后的钙动员。由于干扰素-γ对2MACHLADP的表达没有影响，γ必须通过靶向巨噬细胞HLAII型信号通路的其他部分，通过提高HLAII型信号转导的效率来上调钙动员。
The human macrophage line 2MAC, established recently from peripheral blood, expresses a number of lineage-specific markers as well as a broad array of intercellular adhesion molecules, including high levels of HLA class I and class II. We have presented evidence elsewhere that 2MAC can be productively applied to the study of signal transduction through macrophage HLA class II. Namely, we showed that ligation of 2MAC HLA class II, but not HLA class I, by monoclonal antibody (mAb) elicits an increase in free cytoplasmic Ca2+concentration [Ca2+]i. Moreover, this Ca2+flux appears to be functionally relevant: ligation of HLA-DR, but not HLA class I, by mAb results in the Ca2+mobilization-dependent induction of tissue factor, the high-affinity cellular receptor for factor VII/VIIa. Here we show that 2MAC is uniquely valuable for addressing the efficiency of signal transduction through HLA class II. Namely, we show here that prior culture of 2MAC cells with interferon-γ (IFN-γ) profoundly upregulates subsequent Ca2+mobilization in response to ligation of HLA-DP in the absence of increased cell surface HLA-DP expression. Because IFN-γ has no effect on 2MAC HLA-DP expression, IFN-γ must upregulate Ca2+mobilization by increasing the efficiency of signal transduction through HLA class II (HLA-DP), by targeting some other component of the macrophage HLA class II signalling pathway.