5-hydroxytryptamine induces mast cell adhesion and migration
5-hydroxytryptamine induces mast cell adhesion and migration
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DOI：
10.4049/jimmunol.177.9.6422
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发表时间：
2006-11-01
影响因子：
4.4
通讯作者：
Metcalfe, Dean D.
中科院分区：
文献类型：
--
作者：
Kushnir-Sukhov, Nataliya M.;Gilfillan, Alasdair M.;Metcalfe, Dean D.
神经递质5-羟色胺（5-羟色胺（5-HT））与增强皮肤、肺和胃肠道的炎症反应有关。为了确定5-HT是否部分通过肥大细胞（MC）起作用，我们首先建立了小鼠骨髓源性MC （mBMMC）和人CD34（+）源性MC （huMC）表达多种5-HT受体的mRNA。接下来，我们测定了5-HT对小鼠和人MC脱颗粒、粘附和趋化性的影响。我们没有发现任何证据表明5-HT能使MC脱粒或调节ige依赖性激活。5-HT确实诱导了mBMMC和huMC对纤维连接蛋白的粘附；未成熟和成熟的mBMMC和huMC迁移。趋化性伴随着肌动蛋白聚合。使用受体拮抗剂和百日咳毒素，我们确定5-HT1A是介导5-HT对mc影响的主要受体。来自5-HT1A受体敲除小鼠（5-HT1AR-/-）的mBMMC对5-HT没有反应。5-HT确实诱导了5-HT1AR+/+小鼠真皮中MC的积累，而5-HT1AR-/-小鼠则没有。这些研究首次证明了5-HT对MC的影响。此外，小鼠和人的MC都通过5-HT1A受体对5-HT产生反应。我们的数据与5-HT通过增加组织损伤部位的MC来促进炎症的结论一致。
The neurotransmitter serotonin (5-hydroxytryptamine (5-HT)) is implicated in enhancing inflammatory reactions of skin, lung, and gastrointestinal tract. To determine whether 5-HT acts, in part, through mast cells (MC), we first established that mouse bone marrow-derived MC (mBMMC) and human CD34(+)-derived MC (huMC) expressed mRNA for multiple 5-HT receptors. We next determined the effect of 5-HT on mouse and human MC degranulation, adhesion, and chemotaxis. We found no evidence that 5-HT degranulates MC or modulates IgE-dependent activation. 5-HT did induce mBMMC and huMC adherence to fibronectin; and immature and mature mBMMC and huMC migration. Chemotaxis was accompanied by actin polymerization. Using receptor antagonists and pertussis toxin, we identified 5-HT1A as the principal receptor mediating the effects of 5-HT on MC. mBMMC from the 5-HT1A receptor knockout mouse (5-HT1AR-/-) did not respond to 5-HT. 5-HT did induce accumulation of MC in the dermis of 5-HT1AR+/+ mice, but not in 5-HT1AR-/- mice. These studies are the first to demonstrate an effect of 5-HT on MC. Furthermore, both mouse and human MC respond to 5-HT through the 5-HT1A receptor. Our data are consistent with the conclusion that 5-HT promotes inflammation by increasing MC at the site of tissue injury.