Role of the macrophage in angiogenesis-dependent diseases

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Abstract

It is now well established that the functional domain of the macrophage Mφ extends far beyond its originally recognized role as a scavenger cell. The rich array of secretory products, now numbering in excess of 100 well characterized molecules, and their widespread anatomic distribution and functional heterogeneity, are unmatched by any other cell type (Nathan, 1987). This remarkable diversity enables the Mφ to influence virtually every facet of the immune response and inflammation as well as contribute to the etiology and/or pathogenesis of a number of diseases. Angiogenesis, the process which results in the formation of new capillary blood vessels, is an essential component of a number of important physiological processes (Folkman and Cotran, 1976; Auerbach, 1981; Folkman and Klagsbrun, 1987; Klagsbrun and D’Amore, 1991). Furthermore, when angiogenesis occurs in excess or inappropriately, it can contribute to the etiology and/or pathogenesis of several inflammatory, degenerative and developmental diseases. Mφ are key angiogenesis effector cells that produce a number of growth stimulators and inhibitors, proteolytic enzymes, and cytokines that can influence one or more steps in the angiogenesis cascade. In this review I will summarise the evidence implicating Mφ as important accessory cells in physiological angiogenic responses, and describe how disruption of the coordinate production of Mφ-derived stimulators and inhibitors of angiogenesis contributes to tumor progression and the pathogenesis of chronic inflammatory diseases.