Barthel Steven R, Jarjour Nizar N, Mosher Deane F, Johansson Mats W
Department of Biomolecular Chemistry, University of Wisconsin-Madison, 4285A Medical Sciences Center, 1300 University Avenue, Madison, Wisconsin 53706-1532, USA.
Am J Respir Cell Mol Biol. 2006 Sep;35(3):378-86. doi: 10.1165/rcmb.2006-0027OC. Epub 2006 Apr 6.
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 beta2 integrin and increased expression of alphaMbeta2 (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-alphaM 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-alphaMbeta2. Podosomes, 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 alphaM by CBRM1/5; stimulated alphaMbeta2-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 alphaMbeta2.
哮喘的特征是气道中出现嗜酸性粒细胞。与纯化的血液嗜酸性粒细胞相比，在节段性抗原激发后48小时从气道中纯化的嗜酸性粒细胞表现出通过一种未确定的β2整合素对白蛋白包被表面的更大粘附力以及αMβ2（CD11b/18）表达增加。我们研究了这种高粘附表型的决定因素。气道嗜酸性粒细胞与CBRM1/5抗αM激活敏感抗体的反应性增加，并且对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几种配体。气道嗜酸性粒细胞的增强粘附被抗αMβ2阻断。与血液嗜酸性粒细胞相比，在粘附于VCAM-1的气道嗜酸性粒细胞上，与细胞运动和基质蛋白水解有关的结构——足体更大且更常见。用IL-5孵育血液嗜酸性粒细胞可复制气道嗜酸性粒细胞的表型。也就是说，IL-5增强了CBRM1/5对αM的识别；刺激了αMβ2介导的对VCAM-1、白蛋白、ICAM-1、纤维蛋白原和玻连蛋白的粘附；并增加了在VCAM-1上的足体形成。因此，抗原激发后气道嗜酸性粒细胞的高粘附是由上调和激活的αMβ2介导的。
