Macrophage responses to hypoxia, relevance to disease mechanisms

Macrophages are ubiquitous in the stromal compartment of tissues under norm al physiological conditions and the number of these cells increases markedl y with the onset and progression of many pathological states, The mechanism s underlying this response are well described in such conditions as wound h ealing and malignant tumors, where tissue-specific signals enhance the extr avasation of blood monocytes and their subsequent differentiation into macr ophages. Recent evidence suggests that macrophages may also be stimulated b y microenvironmental factors present in diseased tissues to perform distinc t, 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, express ion of cell surface markers, viability, phagocytosis, metabolic activity, a nd release of cytokines by macrophages. Here we review the evidence for the se macrophage responses to hypoxia, the involvement of co-stimuli, and thei r implications for the role of macrophages in various disease processes. Be cause the intracellular mechanisms mediating the effects of hypoxia on gene expression in other cell types have been characterized recently, we discus s their possible involvement in the effects of hypoxia on gene expression i n macrophages.