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首页> 外文期刊>Clinical and experimental allergy : >Anti-IL-5 attenuates activation and surface density of ??2-integrins on circulating eosinophils after segmental antigen challenge
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Anti-IL-5 attenuates activation and surface density of ??2-integrins on circulating eosinophils after segmental antigen challenge

机译：抗IL-5减弱节段性抗原攻击后循环嗜酸性粒细胞上β2-整合素的活化和表面密度

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Background: IL-5 activates ??M??2 integrin on blood eosinophils in vitro. Eosinophils in bronchoalveolar lavage (BAL) following segmental antigen challenge have activated ??2-integrins. Objective: To identify roles for IL-5 in regulating human eosinophil integrins in vivo. Methods: Blood and BAL eosinophils were analysed by flow cytometry in ten subjects with allergic asthma who underwent a segmental antigen challenge protocol before and after anti-IL-5 administration. Results: Blood eosinophil reactivity with monoclonal antibody (mAb) KIM-127, which recognizes partially activated ??2-integrins, was decreased after anti-IL-5. Before anti-IL-5, surface densities of blood eosinophil ??2, ??M and ??L integrin subunits increased modestly post challenge. After anti-IL-5, such increases did not occur. Before or after anti-IL-5, surface densities of ??2, ??M, ??L and ??D and reactivity with KIM-127 and mAb CBRM1/5, which recognizes high-activity ??M??2, were similarly high on BAL eosinophils 48 h post-challenge. Density and activation state of ??1-integrins on blood and BAL eosinophils were not impacted by anti-IL-5, even though anti-IL-5 ablated a modest post-challenge increase on blood or BAL eosinophils of P-selectin glycoprotein ligand-1 (PSGL-1), a receptor for P-selectin that causes activation of ??1-integrins. Forward scatter of blood eosinophils post-challenge was less heterogeneous and on the average decreased after anti-IL-5; however, anti-IL-5 had no effect on the decreased forward scatter of eosinophils in post-challenge BAL compared with eosinophils in blood. Blood eosinophil KIM-127 reactivity at the time of challenge correlated with the percentage of eosinophils in BAL post-challenge. Conclusion and Clinical Relevance: IL-5 supports a heterogeneous population of circulating eosinophils with partially activated ??2-integrins and is responsible for up-regulation of ??2-integrins and PSGL-1 on circulating eosinophils following segmental antigen challenge but has minimal effects on properties of eosinophils in BAL. Dampening of ??2-integrin function of eosinophils in transit to inflamed airway may contribute to the decrease in lung inflammation caused by anti-IL-5. ? 2012 Blackwell Publishing Ltd.
机译：背景：IL-5在体外激活血液嗜酸性粒细胞上的ΔεM整合素2。节段性抗原攻击后，支气管肺泡灌洗（BAL）中的嗜酸性粒细胞已激活β2-整联蛋白。目的：确定IL-5在体内调节人嗜酸性粒细胞整合素的作用。方法：通过流式细胞术分析了十名过敏性哮喘患者的血液和BAL嗜酸性粒细胞，这些患者在给予抗IL-5前后均接受了分段抗原攻击方案。结果：抗IL-5后，血液中嗜酸性粒细胞与单克隆抗体（mAb）KIM-127的反应性降低，后者可识别部分活化的β2-整合素。在抗IL-5之前，激发后血液嗜酸性粒细胞?? 2，?? M和?? L整联蛋白亚基的表面密度适度增加。抗IL-5后，这种增加没有发生。抗IL-5之前或之后的表面密度分别为?? 2，?? M，?? L和?? D以及与KIM-127和mAb CBRM1 / 5的反应性，从而可识别出高活性的?? M ?? 2攻击后48小时，BAL的嗜酸性粒细胞含量同样较高。抗IL-5不会影响血液和BAL嗜酸性粒细胞上β1-整合素的密度和活化状态，即使抗IL-5消除了血液或PAL选择蛋白糖蛋白配体的BAL嗜酸性粒细胞在攻击后的适度增加-1（PSGL-1），一种P-选择素的受体，可引起?? 1-整合素的活化。攻击后血液嗜酸性粒细胞的前向散射异质性较小，平均在抗IL-5后降低。然而，与血液中的嗜酸性粒细胞相比，抗IL-5对攻击后BAL中嗜酸性粒细胞前向散射的降低没有影响。攻击时的血液嗜酸性粒细胞KIM-127反应性与攻击后BAL中嗜酸性粒细胞的百分比相关。结论和临床意义：IL-5支持部分活化的?? 2-整联蛋白的循环嗜酸性粒细胞的异质群体，并在节段性抗原攻击后负责循环嗜酸性粒细胞上的?? 2-整联蛋白和PSGL-1的上调，但其作用极小对BAL中嗜酸性粒细胞特性的影响。嗜酸性粒细胞转移到发炎的气道中的β2-整合素功能的减弱可能有助于减少由抗IL-5引起的肺部炎症。 ？ 2012布莱克威尔出版有限公司

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