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α(1,3)岩藻糖基转移酶 IV 和 VII 是慢性变应性炎症中嗜碱性粒细胞初始募集所必需的。

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

机构信息

Department of Dermatology, Tokyo Medical and Dental University, Tokyo, Japan.

出版信息

J Invest Dermatol. 2013 Sep;133(9):2161-9. doi: 10.1038/jid.2013.160. Epub 2013 Apr 2.

Abstract

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 in FT-IV and/or FT-VII genes. 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 inflammation in 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.

摘要

嗜碱性粒细胞作为 IgE 介导的慢性过敏炎症(IgE-CAI)发展的起始细胞。然而,嗜碱性粒细胞最初被招募到皮肤中的详细机制尚未阐明。选择素介导白细胞在血管内皮上的捕获和滚动,以实现渗出。选择素的反受体活性受 α(1,3)岩藻糖基转移酶(FTs)IV 和 VII 调节。为了阐明 FTs 调节的选择素配体对初始嗜碱性粒细胞募集的贡献,在缺乏 FT-IV 和/或 FT-VII 基因的小鼠中诱导 IgE-CAI。尽管 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(-/-)小鼠表现出明显受损的炎症。尽管向 FcRγ(-/-)小鼠转移嗜碱性粒细胞可诱导 IgE-CAI,但当从 FT-IV(-/-)/FT-VII(-/-)小鼠转移嗜碱性粒细胞时,这种诱导完全不存在。L-选择素,而不是 P-和 E-选择素阻断 Ab,可抑制体内皮肤炎症。PSGL-1 抗体也可改善皮肤炎症,嗜碱性粒细胞以 PSGL-1 依赖性方式与 L-选择素结合,这受 FT-IV/VII 调节。嗜碱性粒细胞的功能性 PSGL-1 由 FT-IV/VII 产生,随后与 L-选择素结合,可能是初始嗜碱性粒细胞募集和 IgE-CAI 在小鼠中发展所必需的关键步骤之一。

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