Ca2+-dependent functions in peptidoglycan-stimulated mouse dendritic cells.
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.
Xuan
Nguyen T
NT
Department of Physiology, University of Tübingen, Tübingen, Germany.
Shumilina
Ekaterina
E
Matzner
Nicole
N
Zemtsova
Irina M
IM
Biedermann
Tilo
T
Goetz
Friedrich
F
Lang
Florian
F
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
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