title: Ca2+-dependent functions in peptidoglycan-stimulated mouse dendritic cells.
abstract: Peptidoglycans (PGN) from bacterial cell walls may modify the course of an infection with bacterial pathogens. The present study explored the effect of PGN on cytosolic Ca2+ activity, cytokine production and phagocytosis of mouse dendritic cells (DCs), essential cells in the initiation and direction of antigen-specific T cell responses. Exposure of DCs to PGN was followed by a rapid increase in cytosolic Ca2+ activity ([Ca2+]i), which was due to Ca2+ release from intracellular stores and influx of extracellular Ca2+ across the cell membrane. In DCs isolated from Toll-like receptor 2 (TLR2) deficient mice the effect of PGN on [Ca2+]i was dramatically impaired. The PGN-induced increase of [Ca2+]i was dependent on voltage-gated K+ (Kv) channel activity. PGN-induced increase of [Ca2+]i was significantly blunted by margatoxin (MgTx) and perhexiline maleate (PM), inhibitors of Kv1.3 and Kv1.5, respectively. PGN further stimulated the release of tumour necrosis factor alpha (TNFalpha), interleukin-12 (IL-12) and interleukin-10 (IL-10), an effect significantly blunted by PM and the specific blocker of store-operated Ca2+ channels SKF-96365. Moreover, phagocytic capacity was dramatically increased in PGN-stimulated DCs in the presence of either Kv channel inhibitors or SKF-96365. The observations disclose Ca2+ and Kv channel-dependent cytokine production and phagocytosis in PGN-stimulated DCs.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Nguyen T
authors.initials: NT
authors.lastname: Xuan
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Shumilina
authors.forename: Nicole
authors.initials: N
authors.lastname: Matzner
authors.forename: Irina M
authors.initials: IM
authors.lastname: Zemtsova
authors.forename: Tilo
authors.initials: T
authors.lastname: Biedermann
authors.forename: Friedrich
authors.initials: F
authors.lastname: Goetz
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004594:Electrophysiology; D005260:Female; D005269:Femur / Q000166:cytology; D005456:Fluorescent Dyes / Q000378:metabolism; D016257:Fura-2 / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009498:Neurotoxins / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010457:Peptidoglycan / Q000494:pharmacology*; D010480:Perhexiline / Q000031:analogs & derivatives / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D012604:Scorpion Venoms / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000737:chemistry*; D013977:Tibia / Q000166:cytology; D051195:Toll-Like Receptor 2 / Q000276:immunology
chemical_list: D002121:Calcium Channel Blockers; D016207:Cytokines; D004338:Drug Combinations; D005456:Fluorescent Dyes; D007093:Imidazoles; D009498:Neurotoxins; D010457:Peptidoglycan; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; D051195:Toll-Like Receptor 2; C077910:margatoxin; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; C023470:perhexiline maleate; D010480:Perhexiline; D002118:Calcium; D016257:Fura-2