Modulation of ICAM-1 expression in human alveolar macrophages in vitro

Modulation of intercellular adhesion molecule-1 (ICAM-1) expression may be a basic mechanism by which alveolar macrophages (AMs) regulate the inflammatory process in the lung in response to local stimuli. As a model for studying the anti-inflammatory activity of drugs on human AMs, we investigated the effects of fusafungine, an antibiotic for local use by aerosol with anti-inflammatory properties, and that of the glucocorticoid dexamethasone, on ICAM-1 expression induced in vitro by recombinant interferon-gamma (rIFN-gamma). ICAM-1 protein expression was studied on AMs by means of flow cytometry with an anti-CD54 monoclonal antibody; messenger ribonucleic acid (mRNA) levels were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). ICAM-1 was expressed before culture on 21% of bronchoalveolar lavage (BAL) cells, with low intensity. Culture for 24 h with rIFN-gamma resulted in a significant increase in ICAM-1 protein expression (82% of cells were strongly positive). Fusafungine significantly inhibited rIFN-gamma-induced ICAM-1-protein expression on AMs in a concentration-dependent fashion. The mechanism of ICAM-1 downregulation was mainly post-transcriptional, but also partly transcriptional. By contrast, dexamethasone did not influence rIFN-gamma-induced ICAM-1 expression. This in vitro model using human AMs should prove useful for investigating the cellular and molecular targets of anti-inflammatory drugs.