Ca 2+ -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 Ca 2+ 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 Ca 2+ activity ([Ca 2+ ] i ), which was due to Ca 2+ release from intracellular stores and influx of extracellular Ca 2+ across the cell membrane. In DCs isolated from Toll-like receptor 2 (TLR2) deficient mice the effect of PGN on [Ca 2+ ] i was dramatically impaired. The PGN-induced increase of [Ca 2+ ] i was dependent on voltage-gated K + (Kv) channel activity. PGN-induced increase of [Ca 2+ ] 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 α (TNFα), interleukin-12 (IL-12) and interleukin-10 (IL-10), an effect significantly blunted by PM and the specific blocker of store-operated Ca 2+ 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 Ca 2+ and Kv channel-dependent cytokine production and phagocytosis in PGN-stimulated DCs. Copyright © 2009 S. Karger AG, Basel.