Cutting edge: Serotonin is a chemotactic factor for eosinophils and functions additively with eotaxin
Cutting edge: Serotonin is a chemotactic factor for eosinophils and functions additively with eotaxin
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DOI：
10.4049/jimmunol.173.6.3599
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发表时间：
2004-09-15
影响因子：
4.4
通讯作者：
Sriramarao, P
中科院分区：
文献类型：
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作者：
Boehme, SA;Lio, FM;Sriramarao, P
哮喘患者血清中血清素（5-羟色胺，5-HT）水平升高。在这里，我们证明了5-HT作为一种嗜酸性粒细胞化学引诱剂独立地与eotaxin一起起作用。5-HT2A受体拮抗剂（包括MDL-100907和cyproheptadine (CYP)）被发现可以抑制5- ht诱导的迁移，但不能抑制eotaxin诱导的迁移。活体显微镜研究表明，在生理剪切应力条件下，小静脉中嗜酸性粒细胞对5-HT产生滚动反应，而用CYP预处理嗜酸性粒细胞可以阻断这一反应。单独使用CYP可显著抑制ova诱导的野生型小鼠肺嗜酸性粒细胞增多症，并可与CCR3受体拮抗剂联合使用。有趣的是，ova诱导的eotaxin基因敲除（Eot(-/-)）小鼠的肺嗜酸性粒细胞被5-HT2A而不是CCR3受体拮抗剂抑制。这些结果表明，5-HT是一种有效的嗜酸性粒细胞活性化学引诱剂，可以与eotaxin一起起作用，而双重CCR3/5-HT2A受体拮抗剂可能更有效地阻断过敏原诱导的嗜酸性粒细胞募集。
Elevated levels of serotonin (5-hydroxytryptamine, 5-HT) are observed in the serum of asthmatics. Herein, we demonstrate that 5-HT functions independently as an eosinophil chemoattractant that acts additively with eotaxin. 5-HT2A receptor antagonists (including MDL-100907 and cyproheptadine (CYP)) were found to inhibit 5-HT-induced, but not eotaxin-induced migration. Intravital microscopy studies revealed that eosinophils roll in response to 5-HT in venules under conditions of physlological shear stress, which could be blocked by pretreating eosinophils with CYP. OVA-induced pulmonary eosinophilia in wild-type mice was significantly inhibited using CYP alone and maximally in combination with a CCR3 receptor antagonist. Interestingly, OVA-induced pulmonary eosinophilia in eotaxin-knockout (Eot(-/-)) mice was inhibited by treatment with the 5-HT2A but not CCR3 receptor antagonist. These results suggest that 5-HT is a potent eosinophil-active chemoattractant that can function additively with eotaxin and a dual CCR3/5-HT2A receptor antagonist may be more effective in blocking allergen-induced eosinophil recruitment.