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Electric fields are novel determinants of human macrophage functions

巨噬细胞 生物 细胞生物学 巨噬细胞极化 受体 细胞因子 炎症 趋化性 p38丝裂原活化蛋白激酶 信号转导 MAPK/ERK通路 免疫学 生物化学 体外
作者
Joseph Hoare,Ann M. Rajnicek,Colin McCaig,Robert N. Barker,Heather M. Wilson
出处
期刊:Journal of Leukocyte Biology [Wiley]
卷期号:99 (6): 1141-1151 被引量:133
标识
DOI:10.1189/jlb.3a0815-390r
摘要

Abstract Macrophages are key cells in inflammation and repair, and their activity requires close regulation. The characterization of cues coordinating macrophage function has focused on biologic and soluble mediators, with little known about their responses to physical stimuli, such as the electrical fields that are generated naturally in injured tissue and which accelerate wound healing. To address this gap in understanding, we tested how properties of human monocyte-derived macrophages are regulated by applied electrical fields, similar in strengths to those established naturally. With the use of live-cell video microscopy, we show that macrophage migration is directed anodally by electrical fields as low as 5 mV/mm and is electrical field strength dependent, with effects peaking ∼300 mV/mm. Monocytes, as macrophage precursors, migrate in the opposite, cathodal direction. Strikingly, we show for the first time that electrical fields significantly enhance macrophage phagocytic uptake of a variety of targets, including carboxylate beads, apoptotic neutrophils, and the nominal opportunist pathogen Candida albicans, which engage different classes of surface receptors. These electrical field-induced functional changes are accompanied by clustering of phagocytic receptors, enhanced PI3K and ERK activation, mobilization of intracellular calcium, and actin polarization. Electrical fields also modulate cytokine production selectively and can augment some effects of conventional polarizing stimuli on cytokine secretion. Taken together, electrical signals have been identified as major contributors to the coordination and regulation of important human macrophage functions, including those essential for microbial clearance and healing. Our results open up a new area of research into effects of naturally occurring and clinically applied electrical fields in conditions where macrophage activity is critical.
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