| Research 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 were passively sensitized with the serum from atopic asthmatics 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 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 significa
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ntly 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, 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. TNF-a level in the supernatants significantly increased at 120 min after allergen stimulation, and IL-1b level increased in 4 of 15 samples. We also examined the induction of CAMs by TNF-a, IL-1b, and IL-4 on human bronchial tissue. TNF-a and IL-1b increased the expression of ICAM-1, E- selection and VCAM-1, while IL-4 induced only that of VCAM-1. In addition, neutralizing antibody against TNF-a and IL-1b 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 occur in atopic asthma is in part regulated by the expression of ICAM-1, VCAM-1 and E- selectin. Less
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