Department of Dermatology, Tokyo Medical and Dental University, Tokyo, Japan.
J Invest Dermatol. 2013 Sep;133(9):2161-9. doi: 10.1038/jid.2013.160. Epub 2013 Apr 2.
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.
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。