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Electric fields are novel determinants of human macrophage functions
- Source :
- Journal of leukocyte biology. 99(6)
- Publication Year :
- 2015
-
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.
- Subjects :
- 0301 basic medicine
Phagocytosis
medicine.medical_treatment
Immunology
Intracellular Space
Video microscopy
Inflammation
Biology
03 medical and health sciences
Phosphatidylinositol 3-Kinases
Electricity
Cell Movement
medicine
Immunology and Allergy
Macrophage
Humans
Phosphorylation
Receptor
Extracellular Signal-Regulated MAP Kinases
Electrodes
PI3K/AKT/mTOR pathway
Macrophages
Cell Biology
Cell biology
Up-Regulation
Actin Cytoskeleton
030104 developmental biology
Cytokine
Cytokines
Cytokine secretion
Calcium
medicine.symptom
Subjects
Details
- ISSN :
- 19383673
- Volume :
- 99
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of leukocyte biology
- Accession number :
- edsair.doi.dedup.....7988913c50311782fd4bacb3aa8e067e