Epithelial damage in the airways is a feature often observed in patients with asthma and is probably caused by the interaction of epithelial cells with leukocytes. As adhesion molecules are thought to be important in this interaction, we analyzed the expression and modulation of adhesion molecules on primary cultured human bronchial epithelial cells and the bronchial epithelial cell lines BEAS-2B and NCI-H292. E-selectin, P-selectin, and VCAM-1 were absent under basal and stimulated conditions. The adhesion molecules ICAM-1 (CD54), LFA-3 (CD58), and CD44 (H-CAM) were expressed basally on primary cultured human bronchial epithelial cells and the BEAS-2B and NCI-H292 cell lines. CD44 and LFA-3 expression did not change after stimulation with IFN-γ or TNF-α. In contrast, ICAM-1 expression on human bronchial epithelial cells and BEAS-2B cells could be increased by incubation with PMA, IFN-γ, TNF-α, and especially with the combination of IFN-γ and TNF-α. The maximal ICAM-1 expression on both epithelial cell types was obtained with the combination of TNF-α and IFN-γ after 48 h of incubation. The NCI-H292 cell line was different in that it only showed increased ICAM-1 expression after stimulation with PMA and IFN-γ and not by the combination of IFN-γ and TNF-α or with TNF-α alone. In conclusion, the bronchial epithelial cells tested express several adhesion molecules, but only ICAM-1 expression was influenced by inflammatory cytokines.

Because asthmatic patients show increased nerve growth factor (NGF) serum levels, we examined the effect of NGF on airway function. Intravenously administered NGF potentiates the histamine- induced bronchoconstriction with a maximum of over 200% in anesthetized spontaneously breathing guinea pigs. Doses of 8 ng and 80 ng NGF/kg body weight induce a significant hyperresponsiveness to histamine. NGF itself does not affect airway reactivity. Airway hyperresponsiveness is observed 30 min and 3 h after NGF administration, and has disappeared after 24 h. The neurokinin-1 receptor antagonist SR 140333 completely blocks the NGF-induced hyperresponsiveness, pointing to a role for tachykinins. This is the first report showing a direct relation between peripherally administered NGF and airway hyperresponsiveness. Taking into consideration that plasma NGF levels have been shown to be elevated in asthmatic patients, our result points to an important role for NGF in the pathogenesis of asthma.