The Regulation of Macrophage Activities: Role of the Energy-Dependent Intracellular Ca²⁺ Buffering Systems

Abstract

The central role played by phagocytic cells in immunological and inflammatory phenomena is related to their capacity of exhibiting a variety of physiological activities such as locomotion, endocytosis and secretion (8, 9, 18, 19, 22, 24, 28, 51, 53, 55). The mechanisms by which such diverse biological functions are regulated in these cells have only partially been clarified. Recent studies have suggested the possibility that changes in the fluxes of cations across the plasma membrane or other cell membranes, resulting in a variation in steady-state levels of these cations in the cytoplasm, may be involved in the initiation or control of the activity of the phagocytic cells. In particular, it has been demonstrated that an elevation of Ca²⁺ concentration in the cytoplasm of polymorphonuclear leukocytes and macrophages, catalyzed by the ionophore A23187 (35), promotes an increased directional motility, secretion of granule enzymes and O₂ reduction to bactericidal H₂O₂ (30, 35–39, 44, 46, 49, 50, 56, 58, 59). Furthermore, the exposure of polymorphonuclear leukocytes to the complement fragment C5a, to kallikrein or to formylmethionyl peptides, which are all able to stimulate chemotaxis, oxidative metabolism and secretion in these cells (3, 16, 17, 21, 23, 30, 45, 48, 49, 51), has been shown to cause a change in Ca²⁺ fluxes across the plasma membrane (4, 14, 29, 30).