α(1,3) fucosyltransferases-IV and VII are essential for initial recruitment of basophils in chronic allergic inflammation

α(1,3) fucosyltransferases-IV and VII are essential for initial recruitment of basophils in chronic allergic inflammation
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α(1,3)岩藻糖基转移酶-IV和VII对于慢性过敏性炎症中嗜碱性粒细胞的初始募集至关重要

DOI:
10.1038/jid.2013.160
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发表时间:
2013
期刊:
影响因子:
6.5
通讯作者:
Yokozeki H.
Yokozeki H.
中科院分区:
医学1区
文献类型:
--
作者:
Saeki K;Satoh T;Yokozeki H.

文献摘要

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嗜碱性细胞是ige介导的慢性过敏性炎症(IgE-CAI)的启动细胞。然而,嗜碱性粒细胞进入皮肤的初始募集的详细机制尚不清楚。选择素介导白细胞的捕获和在血管内皮上的滚转。选择素的反受体活性受α(1,3)聚焦转移酶(FTs) IV和VII的调控。为了阐明FTs调节的选择素配体在初始嗜碱性粒细胞募集中的作用,我们在缺乏inf - ivand /orFT-VIIgenes的小鼠中诱导了IgE-CAI。虽然FT-IV(-/-)和FT-VII(-/-)小鼠表现出与野生型小鼠相当的皮肤反应,但FT-IV(-/-)/FT-VII(-/-)小鼠表现出明显的炎症受损。虽然将嗜碱性粒细胞转移到FcRγ(-/-)小鼠中可诱导IgE-CAI,但当转移FT-IV(-/-)/FT-VII(-/-)小鼠的嗜碱性粒细胞时,这种诱导作用完全不存在。在体内,l -选择素抑制皮肤炎症,而P-和e -选择素不抑制皮肤炎症。p -选择素糖蛋白-1 (PSGL-1)抗体也能改善皮肤炎症,并且嗜碱性细胞以PSGL-1依赖的方式与l -选择素结合,这是由FT-IV/VII调节的。由嗜碱性粒细胞FT-IV/VII产生的功能性PSGL-1及其随后与l -选择素的结合可能是小鼠初始嗜碱性粒细胞募集和IgE-CAI发展所需的重要步骤之一。
Basophils act as initiator cells for the development of IgE-mediated chronic allergic inflammation (IgE-CAI). However, detailed mechanisms of initial recruitment of basophils into the skin have yet to be clarified. Selectins mediate leukocyte capture and rolling on the vascular endothelium for extravasation. Counter-receptor activity of selectins is regulated by α(1, 3) fucosyltransferases (FTs) IV and VII. To clarify the contribution of selectin ligands regulated by FTs for initial basophil recruitment, IgE-CAI was induced in mice deficient inFT-IVand/orFT-VIIgenes. Although FT-IV(-/-) and FT-VII(-/-) mice exhibited comparable skin responses to wild-type mice, the FT-IV(-/-)/FT-VII(-/-) mice showed significantly impaired inflammation. Although the transfer of basophils to FcRγ(-/-) mice induced IgE-CAI, this induction was completely absent when basophils from FT-IV(-/-)/FT-VII(-/-) mice were transferred. L-selectin, but not P- and E-selectin, blocking Abs inhibited skin inflammationin vivo. P-selectin glycoprotein-1 (PSGL-1) antibody also ameliorated skin inflammation, and basophils were bound to L-selectin in a PSGL-1-dependent manner, which was regulated by FT-IV/VII. Functional PSGL-1 generated by basophil FT-IV/VII and its subsequent binding to L-selectin could be one of the essential steps required for initial basophil recruitment and the development of IgE-CAI in mice.