title: Allergen exposure induces the expression of endothelial adhesion molecules in passively sensitized human bronchus: time course and the role of cytokines.
abstract: To study the mechanisms contributing to the recruitment of a selective leukocyte subset in allergic inflammation involving the airways as may occur in asthma, we examined whether allergic exposure induces the expression of cell adhesion molecules (CAMs) on the bronchial endothelium of passively sensitized human bronchi. Human bronchial tissue obtained from patients undergoing lung cancer surgery was passively sensitized with serum from patients with atopic asthma who were sensitive to house dust mite. We incubated the tissues for 30, 120, 240, and 480 min in the presence or absence of the dust mite allergen. The tissues were stained immunohistochemically for intercellular adhesion molecule 1 (ICAM-1), E-selectin, and vascular cell adhesion molecule 1 (VCAM-1). ICAM-1 was constitutively expressed in both the epithelium and endothelium in all tissues but after allergen stimulation significantly increased at 240 and 480 min. E-selectin expression also existed constitutively and increased significantly at 120 and 240 min with allergen exposure. The constitutive expression of VCAM-1 was less than that of ICAM-1 and E-selectin. Following allergen exposure, VCAM-1 expression increased significantly at 30, 120, 240, and 480 min, and at 480 min reached an almost 3.5-fold increase from baseline expression. The TNF-alpha level in the supernatants significantly increased at 120 min after allergen stimulation, and the interleukin (IL)-1beta level increased in 4 of 15 samples. We also examined the induction of CAMs by TNF-alpha, IL-1beta, and IL-4 on human bronchial tissue. TNF-alpha and IL-1beta increased the expression of ICAM-1, E-selectin, and VCAM-1, whereas IL-4 induced only that of VCAM-1. In addition, neutralizing antibody against TNF-alpha and IL-1beta partially blocked the upregulation of CAMs on passively sensitized bronchial tissue after allergen exposure. Thus, both an IgE-dependent allergic response and selected cytokines are able to upregulate endothelial CAMs in human bronchial tissue. These observations provide further evidence that leukocyte infiltration into the site of allergic inflammation as occurs in atopic asthma is in part regulated by the expression of ICAM-1, VCAM-1, and E-selectin.
authors.affiliation: First Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Hirata
authors.forename: H
authors.initials: H
authors.lastname: Kohrogi
authors.forename: H
authors.initials: H
authors.lastname: Iwagoe
authors.forename: E
authors.initials: E
authors.lastname: Goto
authors.forename: J
authors.initials: J
authors.lastname: Hamamoto
authors.forename: K
authors.initials: K
authors.lastname: Fujii
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: O
authors.initials: O
authors.lastname: Kawano
authors.forename: M
authors.initials: M
authors.lastname: Ando
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000485:Allergens / Q000276:immunology*; D001980:Bronchi / Q000737:chemistry* / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000032:analysis*; D016207:Cytokines / Q000502:physiology*; D019040:E-Selectin / Q000032:analysis; D004727:Endothelium / Q000737:chemistry / Q000276:immunology; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007700:Kinetics; D008175:Lung Neoplasms / Q000601:surgery; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
chemical_list: D000485:Allergens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4