THE INCREASED EXPRESSION OF HLA-DR AND ICAM-1 MOLECULES BY HUMAN BRONCHIAL EPITHELIAL-CELLS, INDUCED BY ACTIVATED MONONUCLEAR-CELLS, IS DOWN-REGULATED BY NEDOCROMIL SODIUM

To test the hypothesis that mononuclear cell products could increase t he expression of HLA-DR and ICAM-1 molecules in bronchial epithelial c ells (BECs), subconfluent cultures of human BECs, obtained from surgic ally resected bronchi, were incubated with PHA-activated blood mononuc lear cell conditioned media (BCM-CM) or recombinant IFN-gamma. The pre sence of HLA-DR and ICAM-1 molecules on BECs was then evaluated by spe cific antibody staining and flow-cytometry analysis. The addition to B EC cultures of different concentrations of PHA-stimulated BMC-CM, or o f IFN-gamma, induced a dose-dependent increase of HLA-DR and ICAM-1 ex pression, while no effect was observed with unstimulated BMC-CM. The a bility of nedocromil sodium and, as control, of dexamethasone, to prev ent the upregulation of HLA-DR and ICAM-1 expression on BECs was then tested. Increasing concentrations (10(-7) to 10(-4) M) of nedocromil s ignificantly inhibited HLA-DR and ICAM-1 expression by BECs in a dose- dependent fashion. A similarly dose-dependent inhibitory effect was al so observed with dexamethasone, which however, was less active than ne docromil on HLA-DR expression and more active on ICAM-1 expression. Fi nally, nedocromil and dexamethasone showed a significant synergistic e ffect on the expression of both cell surface molecules at the lowest c oncentrations tested.