Inhibitory effect of carotenoids on the degranulation of mast cells via suppression of antigen-induced aggregation of high affinity IgE receptors.
Carotenoids have been demonstrated to possess antioxidative and anti-inflammatory effects. However, there is no report that the effects of carotenoids on degranulation of mast cell is critical for type I allergy. In this study, we focused on the effect of carotenoids on antigen-induced degranulation of mast cells. Fucoxanthin, astaxanthin, zeaxanthin, and beta-carotene significantly inhibited the antigen-induced release of beta-hexosaminidase in rat basophilic leukemia 2H3 cells and mouse bone marrow-derived mast cells. Those carotenoids also inhibited antigen-induced aggregation of the high affinity IgE receptor (Fc epsilonRI), which is the most upstream of the degranulating signals of mast cells. Furthermore, carotenoids inhibited Fc epsilonRI-mediated intracellular signaling, such as phosphorylation of Lyn kinase and Fyn kinase. It suggests that the inhibitory effect of carotenoids on the degranulation of mast cells were mainly due to suppressing the aggregation of Fc epsilonRI followed by intracellular signaling. In addition, those carotenoids inhibited antigen-induced translocation of Fc epsilonRI to lipid rafts, which are known as platforms of the aggregation of Fc epsilonRI. We assume that carotenoids may modulate the function of lipid rafts and inhibit the translocation of Fc epsilonRI to lipid rafts. This is the first report that focused on the aggregation of Fc epsilonRI to investigate the mechanism of the inhibitory effects on the degranulation of mast cells and evaluated the functional activity of carotenoids associated with lipid rafts.
Sakai
Shota
S
Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502.
Sugawara
Tatsuya
T
Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502. Electronic address: sugawara@kais.kyoto-u.ac.jp.
Matsubara
Kiminori
K
Department of Human Life Sciences Education, Graduate School of Education, Hiroshima University, 1-1-1 Kagamiyama, Higashi-Hiroshima 739-8524, Japan.
Hirata
Takashi
T
Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502.
D000818:Animals; D000941:Antigens / Q000276:immunology*; D002338:Carotenoids / Q000276:immunology / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects* / Q000276:immunology; D002460:Cell Line; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D039821:Monoterpenes / Q000494:pharmacology; D051381:Rats; D011940:Receptor Aggregation; D017455:Receptors, IgE / Q000737:chemistry / Q000276:immunology*; D015398:Signal Transduction / Q000502:physiology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D000941:Antigens; D039821:Monoterpenes; D017455:Receptors, IgE; D002338:Carotenoids; D001619:beta-N-Acetylhexosaminidases
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