期刊
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
卷 35, 期 3, 页码 378-386出版社
AMER THORACIC SOC
DOI: 10.1165/rcmb.2006-0027OC
关键词
adhesion molecules; cell trafficking; eosinophils; human
资金
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR003186] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [T32HL007899, P50HL056396] Funding Source: NIH RePORTER
- NCRR NIH HHS [M01 RR03186] Funding Source: Medline
- NHLBI NIH HHS [HL56396, T32 HL007899, P50 HL056396] Funding Source: Medline
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.
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