title: Extracellular magnesium and calcium blockers modulate macrophage activity.
abstract: Magnesium (Mg) possesses anti-inflammatory properties, partly because it antagonizes calcium (Ca) and inhibits L-type Ca channels. Our aim was to determine the effects of different concentrations of extracellular Mg, with or without Ca-channel blockers, in macrophages. A macrophage-like cell line J774.E was cultured in different concentrations of extracellular Mg and exposed to i) the phorbol ester PMA to induce the production of reactive oxygen species ii) lipopolysaccharide to induce the production of pro-inflammatory cytokines, or iii) ovalbumin to study endocytosis. The Ca antagonists verapamil and/or TMB-8 were used to interfere with Ca homeostasis. Different concentrations of extracellular Mg did not impact on endocytosis, while Ca antagonists markedly decreased it. Low extracellular Mg exacerbated, whereas Ca antagonists inhibited, PMA-induced production of free radicals. Ca blockers prevented lipopolysaccharide-induced transcription and release of IL-1β, IL-6 and TNF-α, while extracellular Mg had only a marginal effect. Ca channel inhibitors markedly reduced the activity of J774.E cells, thus underscoring the critical role of Ca in the non-specific immune response, a role which was, in some instances, also modulated by extracellular Mg.
authors.affiliation: Department of Immunology, Pathophysiology and Veterinary Preventive Medicine, Wroclaw University of Environmental and Life Science, C.K. Norwida 31, 50-375 Wroclaw, Poland.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Libako
authors.affiliation: Department of Immunology, Pathophysiology and Veterinary Preventive Medicine, Wroclaw University of Environmental and Life Science, C.K. Norwida 31, 50-375 Wroclaw, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Nowacki
authors.affiliation: Department of Biomedical and Clinical Sciences L. Sacco, Università di Milano, Via GB Grassi, 74 Milano, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Castiglioni
authors.affiliation: Inra, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, Clermont Université, Unité de Nutrition Humaine, BP 10448, Clermont-Ferrand, France.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Mazur
authors.affiliation: Department of Biomedical and Clinical Sciences L. Sacco, Università di Milano, Via GB Grassi, 74 Milano, Italy.
authors.forename: Jeanette A M
authors.initials: JA
authors.lastname: Maier
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013329:Structure-Activity Relationship; D014700:Verapamil / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D014700:Verapamil; D008274:Magnesium
keywords: calcium; cytokines; macrophages; magnesium; reactive oxygen species