Antigen-independent induction of histamine synthesis by immunoglobulin E in mouse bone marrow-derived mast cells.
Immunoglobulin (Ig)E-mediated activation of mast cells has long been thought to occur only when Fc(epsilon)RI receptor-bound IgE is cross-linked via multivalent antigens. However, recent studies have raised the possibility that mast cells may be activated by the binding of IgE to the Fc(epsilon)RI receptor in the absence of antigen. Here we demonstrate that IgE binding without antigen induces the expression of histidine decarboxylase (HDC) in mouse interleukin (IL)-3-dependent bone marrow-derived mast cells (BMMCs). The induction of HDC by the binding of IgE was found to require an influx of extracellular calcium ions, which was attenuated by pretreatment with U73122, a phospholipase C inhibitor. Furthermore, the increase in HDC activity upon sensitization with IgE was completely suppressed by pretreatment of BMMCs with protein kinase C inhibitors, such as H7, staurosporine, and Gö6976. In addition, immediate activation of the tyrosine kinase Lyn was not detectable upon treatment with IgE. These results suggest that the binding of IgE to its receptor in the absence of antigen results in de novo synthesis of HDC in BMMCs through a signaling pathway distinct to that operating during antigen-stimulated Fc(epsilon)RI activation.
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Satoshi
S
Tanaka
Yuhji
Y
Takasu
Sonoko
S
Mikura
Norio
N
Satoh
Atsushi
A
Ichikawa
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D020013:Calcium Signaling; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000096:biosynthesis*; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism*; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011760:Pyrrolidinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017455:Receptors, IgE / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D019061:src-Family Kinases / Q000378:metabolism
D000941:Antigens; D004791:Enzyme Inhibitors; D004963:Estrenes; D007377:Interleukin-3; D011760:Pyrrolidinones; D012333:RNA, Messenger; D017455:Receptors, IgE; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D007073:Immunoglobulin E; D000001:Calcimycin; D006632:Histamine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; D006640:Histidine Decarboxylase; D013755:Tetradecanoylphorbol Acetate