ICAM-1-dependent pathways regulate colonic eosinophilic inflammation
ICAM-1-dependent pathways regulate colonic eosinophilic inflammation
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DOI：
10.1189/jlb.1105643
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发表时间：
2006-08-01
影响因子：
5.5
通讯作者：
Hogan, Simon P.
中科院分区：
文献类型：
--
作者：
Forbes, Elizabeth;Hulett, Mark;Hogan, Simon P.
嗜酸性粒细胞炎症是许多嗜酸性粒细胞相关胃肠道（EGID）疾病的共同特征。嗜酸性粒细胞迁移到胃肠道的中心是整合素介导的与粘附分子的相互作用。虽然调节嗜酸性粒细胞归巢到小肠的机制已开始阐明，负责嗜酸性粒细胞运输到大肠的粘附途径是未知的。我们研究了粘附途径在稳态和疾病过程中嗜酸性粒细胞向大肠的募集中的作用。首先，使用半抗原诱导的结肠损伤模型，我们证明与小肠相反，嗜酸性粒细胞向结肠的募集是由β（7）-整联蛋白地址素细胞粘附分子-1-独立途径调节的。通过流式细胞术分析结肠嗜酸性粒细胞上整合素表达的特征显示结肠CC趋化因子受体3（+）嗜酸性粒细胞表达细胞间粘附分子-1（ICAM-1）反受体整合素α（L）、α（M）和β（2）。使用ICAM-1缺陷小鼠和抗ICAM-1中和抗体，我们发现半抗原诱导的结肠嗜酸性粒细胞炎症严重依赖于ICAM-1。这些研究表明，β 2-整联蛋白/ICAM-1依赖性途径是与结肠损伤相关的GI炎症期间嗜酸性粒细胞募集到结肠中不可或缺的。J. Leukoc. 80：330-341; 2006.
Eosinophilic inflammation is a common feature of numerous eosinophil-associated gastrointestinal (EGID) diseases. Central to eosinophil migration into the gastrointestinal tract are the integrin-mediated interactions with adhesion molecules. Although the mechanisms regulating eosinophil homing into the small intestine have begun to be elucidated, the adhesion pathways responsible for eosinophil trafficking into the large intestine are unknown. We investigated the role of adhesion pathways in eosinophil recruitment into the large intestine during homeostasis and disease. First, using a hapten-induced colonic injury model, we demonstrate that in contrast to the small intestine, eosinophil recruitment into the colon is regulated by a (beta(7)-integrin addressin cell adhesion molecule-1-independent pathway. Characterization of integrin expression on colonic eosinophils by flow cytometry analysis revealed that colonic CC chemokine receptor 3(+) eosinophils express the intercellular adhesion molecule-1 (ICAM-1) counterreceptor integrins alpha(L), alpha(M), and beta(2). Using ICAM-1-deficient mice and anti-ICAM-1 neutralizing antibodies, we show that hapten-induced colonic eosinophilic inflammation is critically dependent on ICAM-1. These studies demonstrate that (beta(2)-integrin/ICAM-1-dependent pathways are integral to eosinophil recruitment into the colon during GI inflammation associated with colonic injury. J. Leukoc. Biol. 80: 330-341; 2006.