To evaluate the factors controlling migration of leukocytes into pulmonary airway epithelium, we determined the biochemical mechanisms responsible for the regulation of intercellular adhesion molecule-1 (ICAM-1) expression on cultured monolayers of human tracheal epithelial cells (HTECs) or SV40 virus- transformed human bronchial epithelial cells (BEAS-2B). Validation experiments with human umbilical vein endothelial cells (HUVECs) demonstrated little detectable ICAM-1 expression on unstimulated cells or on cells incubated with interferon-γ (IFN-γ), but HUVEC monolayers responded to interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α) with significant increases in ICAM-1 and ICAM-1-dependent adherence of polymorphonuclear leukocytes (PMNs). HTEC monolayers also exhibited no significant basal ICAM-1 expression but, in contrast to HUVEC monolayers, had marked increases in ICAM-1 expression and ICAM-1-dependent PMN adherence only after incubation with IFN-γ (and not after IL-1β or TNF-α) treatment. BEAS-2B cells also exhibited relatively selective IFN-γ stimulation of ICAM- 1 expression and ICAM-1-dependent PMN adherence but (like late passage HTEC) showed significant basal ICAM-1 expression. Differences in IFN-γ effect on ICAM-1 levels between HUVEC and HTEC monolayers were not due to differences in number or responsiveness of IFN-γ receptors, because both cell types exhibited a similar number of receptors and other IFN-γ-dependent responses of HUVECs remained active. In all analyses, ICAM-1 mRNA levels correlated closely with detection of ICAM-1 on the cell surface. The results indicate that ICAM-1 is expressed on human airway epithelial cells and that ICAM-1- dependent mechanisms may mediate PMN adherence to these cells. As in other cell types, induction of ICAM-1 in airway epithelial cells appears to be transcriptionally regulated, but in contrast to endothelial cells, the induction of ICAM-1 in airway epithelial cells is selectively responsive to IFN-γ.
|Journal||American Journal of Physiology - Lung Cellular and Molecular Physiology|
|Issue number||1 7-1|
|State||Published - Jan 1 1992|
- polymorphonuclear leukocyte adherence
- tumor necrosis factor-α
- vascular endothelial cells