Role of the Macrophage in the Regulation of Physiological and Pathological Angiogenesis

Angiogenesis, the growth of new capillary blood vessels, is one of the most pervasive and essential biological processes encountered in the mammalian organism (Auerbach, 1981; Folkman and Cotran, 1978; Folkman, 1985; Folkman and Klagsbrun, 1987). A wide array of physiological and pathological conditions such as embryonic development, the formation of inflammatory granulation tissue during wound repair, and the growth of malignant solid tumors are strictly dependent upon the recruitment of new capillaries. In the adult organism, angiogenesis occurs infrequently yet can be rapidly induced by a number of physiologic stimuli. In recent years the macrophage (Mo) has been shown to be one of the key players in the regulation of physiologic and pathologic angiogenesis (Polverini et al., 1977b; Polverini, 1989). These cells perform multiple diverse functions within the immune system and influence the course of certain primitive yet fundamentally important processes such as nonspecific inflammation and wound healing (Leibovich and Ross, 1975). This functional versatility is due in large part to their ability to respond rapidly to environmental signals that induce them to acquire new or enhanced properties (Nathan, 1987). One of these functions is the capacity to induce and subsequently down-regulate the formation of new capillary blood vessels.