Ca2+ influx-mediated histamine synthesis and IL-6 release in mast cells activated by monomeric IgE.
We previously demonstrated that histamine synthesis is drastically induced upon sensitization with an anti-DNP IgE clone, SPE-7, in IL-3-dependent mouse bone marrow derived mast cells (BMMC). We found that Ca2+ mobilization induced by SPE-7 exhibited a similar profile to the capacitative Ca2+ entry evoked by thapsigargin. Potentials for activation of mast cells were found to vary between different IgE clones, and a monovalent hapten, DNP-lysine, suppressed the activation induced by SPE-7. Ca2+ mobilization induced by SPE-7 was suppressed potently by the specific store-operated Ca2+ channel inhibitor, SK&F 96365, but not at all by Ca2+ channel inhibitors with more broad spectrum, La3+ and Gd3+, whereas the Ca2+ mobilization induced by Ag stimulation was suppressed by these inhibitors. Ca2+ mobilization was also induced by SPE-7 in in vitro differentiated mast cells, although the increases in histamine synthesis and IL-6 release were smaller than those in BMMC. These results suggest that Ca2+ influx operated by a distinct mechanism from that in Ag stimulation is essential for increased histamine synthesis and IL-6 release in mast cells.
Tanaka
Satoshi
S
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Mikura
Sonoko
S
Hashimoto
Eri
E
Sugimoto
Yukihiko
Y
Ichikawa
Atsushi
A
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000096:biosynthesis*; D007073:Immunoglobulin E / Q000276:immunology*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D015850:Interleukin-6; D007073:Immunoglobulin E; D006632:Histamine; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D002118:Calcium