Monick M M, Carter A B, Hunninghake G W
Department of Medicine, University of Iowa College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa 52242, USA.
J Biol Chem. 1999 Jun 18;274(25):18075-80. doi: 10.1074/jbc.274.25.18075.
Although many functions of human alveolar macrophages are altered compared with their precursor cell, the blood monocyte (monocyte), the reason(s) for these functional changes have not been determined. We recently reported that human alveolar macrophages do not express AP-1 DNA binding activity (Monick, M. M., Carter, A. B., Gudmundsson, G., Geist, L. J., and Hunninghake, G. W. (1998) Am. J. Physiol. 275, L389-L397). To determine why alveolar macrophages do not express AP-1 DNA binding activity, we first showed that there was not a decrease in expression of the FOS and JUN proteins that make up the AP-1 complex. There was, however, a significant difference in the amounts of the nuclear protein, REF-1 (which regulates AP-1 DNA binding by altering the redox status of FOS and JUN proteins), in alveolar macrophages compared with monocytes. In addition, in vitro differentiation of monocytes to a macrophage-like cell resulted in decreased amounts of REF-1. Finally, addition of REF-1 from activated monocytes to alveolar macrophage nuclear proteins resulted in a marked increase in AP-1 DNA binding. These studies strongly suggest that the process of differentiation of monocytes into alveolar macrophages is associated with a loss of REF-1 and AP-1 activity. This observation may explain, in part, some of the functional differences observed for alveolar macrophages compared with monocytes.
尽管与它们的前体细胞——血液单核细胞（单核细胞）相比，人类肺泡巨噬细胞的许多功能发生了改变，但这些功能变化的原因尚未确定。我们最近报道，人类肺泡巨噬细胞不表达AP-1 DNA结合活性（莫尼克，M.M.，卡特，A.B.，古德蒙德松，G.，盖斯特，L.J.，和亨宁哈克，G.W.（1998年）《美国生理学杂志》275，L389-L397）。为了确定肺泡巨噬细胞为何不表达AP-1 DNA结合活性，我们首先表明，构成AP-1复合物的FOS和JUN蛋白的表达没有减少。然而，与单核细胞相比，肺泡巨噬细胞中核蛋白REF-1（通过改变FOS和JUN蛋白的氧化还原状态来调节AP-1 DNA结合）的量存在显著差异。此外，单核细胞体外分化为巨噬细胞样细胞导致REF-1的量减少。最后，将活化单核细胞中的REF-1添加到肺泡巨噬细胞核蛋白中导致AP-1 DNA结合显著增加。这些研究强烈表明，单核细胞分化为肺泡巨噬细胞的过程与REF-1和AP-1活性的丧失有关。这一观察结果可能部分解释了与单核细胞相比，肺泡巨噬细胞所观察到的一些功能差异。
