Intracellular Calcium as a Regulator of Polarization and Target Reprogramming of Macrophages

Macrophage metabolic plasticity providing their polarization towards classically (M1) or alternatively (M2) activated cells is an important element of the initiation, development, and resolving or inflammation-linked pathologies. The prevalence of M1 or M2 types of macrophages during different stages of diseases supports increased inflammation and phagocytosis or tissue repair, respectively. An imbalance leading to a shift toward an M1- or M2-dominant state is associated with a chronic pathological process. This characterizes the regulation of macrophage phenotypes as a prospective strategy in the treatment of various diseases and makes it relevant to a deep understanding of the mechanisms defining cell polarization. According to the central role of calcium signaling in cell metabolism, changes in calcium homeostasis are closely linked to the regulation of polarization. The exact balance between calcium flows across plasma and intracellular membranes provided by a number of receptors and channels, as well as the differences in the calcium-buffering capability of endoplasmic reticulum and mitochondria, are able to influence macrophage polarization towards an M1 or M2 phenotype. This review focuses on the role of the calcium homeostasis system in macrophage functionality and calcium-induced changes in macrophage metabolism that forms the basis of target disease therapy.