Lewis J S, Lee J A, Underwood J C, Harris A L, Lewis C E
Department of Pathology, Sheffield University Medical School, United Kingdom.
J Leukoc Biol. 1999 Dec;66(6):889-900. doi: 10.1002/jlb.66.6.889.
Macrophages are ubiquitous in the stromal compartment of tissues under normal physiological conditions and the number of these cells increases markedly with the onset and progression of many pathological states. The mechanisms underlying this response are well described in such conditions as wound healing and malignant tumors, where tissue-specific signals enhance the extravasation of blood monocytes and their subsequent differentiation into macrophages. Recent evidence suggests that macrophages may also be stimulated by microenvironmental factors present in diseased tissues to perform distinct, tissue-specific activities. One such factor, hypoxia (low oxygen tension), results from insufficient vascular perfusion of a given tissue. Various studies have shown that experimental hypoxia alters the morphology, expression of cell surface markers, viability, phagocytosis, metabolic activity, and release of cytokines by macrophages. Here we review the evidence for these macrophage responses to hypoxia, the involvement of co-stimuli, and their implications for the role of macrophages in various disease processes. Because the intracellular mechanisms mediating the effects of hypoxia on gene expression in other cell types have been characterized recently, we discuss their possible involvement in the effects of hypoxia on gene expression in macrophages.
在正常生理条件下，巨噬细胞广泛存在于组织的基质区室中，并且随着许多病理状态的发生和发展，这些细胞的数量会显著增加。在伤口愈合和恶性肿瘤等情况下，这种反应的潜在机制已有详细描述，其中组织特异性信号会增强血液单核细胞的渗出及其随后分化为巨噬细胞的过程。最近的证据表明，巨噬细胞也可能受到病变组织中存在的微环境因素刺激，从而执行独特的、组织特异性的活动。其中一个因素是缺氧（低氧张力），它是由特定组织的血管灌注不足导致的。各种研究表明，实验性缺氧会改变巨噬细胞的形态、细胞表面标志物的表达、活力、吞噬作用、代谢活性以及细胞因子的释放。在此，我们综述巨噬细胞对缺氧反应的证据、共刺激因子的参与情况及其对巨噬细胞在各种疾病过程中作用的影响。由于最近已阐明介导缺氧对其他细胞类型基因表达影响的细胞内机制，我们将讨论它们可能参与缺氧对巨噬细胞基因表达的影响。
