Premium
Distinct roles of Ca 2+ mobilization and G protein usage on regulation of Toll‐like receptor function in human and murine mast cells
Author(s) -
Zaidi Asifa K.,
Thangam Elden Retna Raj B.,
Ali Hydar
Publication year - 2006
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2006.02450.x
Subject(s) - toll , receptor , microbiology and biotechnology , mast (botany) , function (biology) , mobilization , toll like receptor , biology , mast cell , chemistry , immunology , biochemistry , innate immune system , political science , law
Summary Toll‐like receptors (TLRs) expressed in mast cells play important roles in orchestrating host defence against bacterial pathogens. Previous studies demonstrated that TLR2 agonist tripalmitoyl‐ S ‐glycero‐Cys‐(Lys) 4 (Pam 3 Cys) stimulates both degranulation and cytokine production in human mast cells but only induces cytokine production in murine mast cells. To determine the molecular basis for this difference, we utilized a human mast cell line LAD 2, murine lung and bone marrow‐derived mast cells (MLMC and BMMC). We found that Pam 3 Cys caused a sustained Ca 2+ mobilization and degranulation in LAD 2 mast cells but not in MLMC or BMMC. Despite these differences, Pam 3 Cys stimulated equivalent chemokine CCL2 generation in all mast cell types tested. Cyclosporin A (CsA), an inhibitor of Ca 2+ /calcineurin‐mediated nuclear factor of activated T cells (NFAT) activation, blocked chemokine production in LAD 2 but not in MLMC or BMMC. In contrast, inhibitors of nuclear factor kappa B (NF‐κB) completely blocked CCL2 production in MLMC and BMMC but not in LAD 2 mast cells. Pertussis toxin and U0126, which, respectively, inhibit Gα i, extracellular signal‐regulated kinase (ERK) phosphorylation substantially inhibited Pam 3 Cys‐induced CCL2 generation in LAD 2 mast cells but had little or no effect on chemokine generation in MLMC and BMMC. These findings suggest that TLR2 activation in human LAD 2 mast cells and MLMC/BMMC promotes the release of different classes of mediators via distinct signalling pathways that depend on Ca 2+ mobilization and G protein usage.