ALLERGEN EXPOSURE INDUCES THE EXPRESSION OF ENDOTHELIAL ADHESION MOLECULES IN PASSIVELY SENSITIZED HUMAN BRONCHUS - TIME-COURSE AND THE ROLE OF CYTOKINES

To study the mechanisms contributing to the recruitment of a selective leukocyte subset in allergic inflammation involving the airways as ma y occur in asthma, we examined whether allergic exposure induces the e xpression of fell adhesion molecules (CAMs) on The bronchial endotheli um of passively sensitized human bronchi. Human bronchial tissue obtai ned from patients undergoing lung cancer surgery was passively sensiti zed with serum from patients with atopic asthma who were sensitive to house dust mite. We incubated the tissues for 30, 120, 240, and 480 mi n in the presence or absence of the dust mite allergen. The tissues we re 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 endoth elium in all tissues but after allergen stimulation significantly incr eased at 240 and 480 min. E-selectin expression also existed constitut ively and increased significantly at 120 and 240 min with allergen exp osure, The constitutive expression of VCAM-1 was less than that of ICA M-1 and E-selectin. Following allergen exposure VCAM-1 expression incr eased significantly at 30, 120, 240, and 480 min, and at 480 min reach ed an almost 3.5-fold increase from baseline expression. The TNF-alpha level in the supernatants significantly increased al 120 min after al lergen stimulation, and the interleukin (IL)-1 beta level increased in 4 of 15 samples, We also examined the induction of CAMs by TNF-alpha, IL-1 beta P, and IL-4 on human bronchial tissue. TNF-alpha and IL-1 b eta increased the expression of ICAM-1, E-selectin, and VCAM-1, wherea s IL-4 induced only that of VCAM-1. In addition, neutralizing antibody against TNF-alpha and IL-1 beta partially blocked die 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, Th ese observations provide further evidence that leukocyte infiltration into the site of allergic inflammation as occurs in atopic asthma is i n part regulated by the expression of ICAM-1, VCAM-1, and E-selectin.