Dissection of the hyperadhesive phenotype of airway eosinophils in asthma.
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.
Barthel
Steven R
SR
Department of Biomolecular Chemistry, University of Wisconsin-Madison, 4285A Medical Sciences Center, 1300 University Avenue, Madison, Wisconsin 53706-1532, USA.
Jarjour
Nizar N
NN
Mosher
Deane F
DF
Johansson
Mats W
MW
D000906:Antibodies / Q000494:pharmacology; D001249:Asthma / Q000276:immunology*; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D005340:Fibrinogen / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D015848:Interleukin-5 / Q000494:pharmacology; D008024:Ligands; D016177:Macrophage-1 Antigen / Q000032:analysis / Q000378:metabolism*; D010641:Phenotype; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology; D019096:Vitronectin / Q000276:immunology
D000906:Antibodies; D018821:CD18 Antigens; D015848:Interleukin-5; D008024:Ligands; D016177:Macrophage-1 Antigen; D019010:Vascular Cell Adhesion Molecule-1; D019096:Vitronectin; D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen