Dissection of the hyperadhesive phenotype of airway eosinophils in asthma
Dissection of the hyperadhesive phenotype of airway eosinophils in asthma
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DOI：
10.1165/rcmb.2006-0027oc
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发表时间：
2006-09-01
影响因子：
6.4
通讯作者：
Johansson, Mats W.
中科院分区：
文献类型：
--
作者：
Barthel, Steven R.;Larjour, Nizar N.;Johansson, Mats W.
哮喘的特征是气道中出现嗜酸性粒细胞。节段性抗原攻击后 48 小时从气道纯化的嗜酸性粒细胞被描述为与纯化的血液嗜酸性粒细胞相比，通过未识别的 β2 整联蛋白对白蛋白包被的表面表现出更大的粘附性，并且 αMβ2 (CD11b/18) 的表达增加。我们研究了这种超粘附表型的决定因素。气道嗜酸性粒细胞表现出与 CBRM1/5 抗 α M 激活敏感抗体的反应性增加，以及对 VCAM-1 (CD106) 和多种配体（包括白蛋白、ICAM-1 (CD54)、纤维蛋白原和玻连蛋白）的粘附增强。纯化的血液嗜酸性粒细胞不粘附于后者不同的配体。气道嗜酸性粒细胞的增强粘附被抗 α M beta 2 阻断。与血液嗜酸性粒细胞相比，粘附 VCAM-1 的气道嗜酸性粒细胞中的多粒体（与细胞运动和基质蛋白水解有关的结构）更大且更常见。血液嗜酸性粒细胞与 IL-5 的孵育复制了气道嗜酸性粒细胞的表型。即IL-5增强了CBRM1/5对αM的识别；刺激 alpha M beta 2 介导的对 VCAM-1、白蛋白、ICAM-1、纤维蛋白原和玻连蛋白的粘附；并增加 VCAM-1 上足小体的形成。因此，抗原攻击后气道嗜酸性粒细胞的过度粘附是由上调和激活的αMβ2介导的。
Asthma is characterized by appearance of eosinophils in the airway. Eosinophils purified from the airway 48 h after segmental antigen challenge are described as exhibiting greater adhesion to albumin-coated surfaces via an unidentified beta 2 integrin and increased expression of alpha M beta 2 (CD11b/18) compared with purified blood eosinophils. We have investigated the determinants of this hyperadhesive phenotype. Airway eosinophils exhibited increased reactivity with the CBRM1/5 anti-alpha M activation-sensitive antibody as well as enhanced adhesion to VCAM-1 (CD106) and diverse ligands, including albumin, ICAM-1 (CD54), fibrinogen, and vitronectin. Purified blood eosinophils did not adhere to the latter diverse ligands. Enhanced adhesion of airway eosinophils was blocked by anti-alpha M beta 2. Poclosomes, structures implicated in cell movement and proteolysis of matrix proteins, were larger and more common on airway eosinophils adherent to VCAM-1 when compared with blood eosinophils. Incubation of blood eosinophils with IL-5 replicated the phenotype of airway eosinophils. That is, IL-5 enhanced recognition of alpha M by CBRM1/5; stimulated alpha M beta 2-mediated adhesion to VCAM-1, albumin, ICAM-1, fibrinogen, and vitronectin; and increased podosome formation on VCAM-1. Thus, the hyperadhesion of airway eosinophils after antigen challenge is mediated by upregulated and activated alpha M beta 2.