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

• Published in: The European respiratory journal Vol. 9; no. 3; pp. 463 - 471
• Main Authors: Fattal-German, M, Ladurie, FL, Cerrina, J, Lecerf, F, Berrih-Aknin, S
• Format: Journal Article
• Language: English
• Published: Leeds Eur Respiratory Soc 01-03-1996; Maney
• Subjects: Aerosols - pharmacology; Anti-Bacterial Agents - pharmacology; Anti-Inflammatory Agents - pharmacology; Base Sequence; Biological and medical sciences; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid - cytology; Cells, Cultured; Depsipeptides; Dexamethasone - pharmacology; Down-Regulation; Fluorescent Antibody Technique; Fusarium; Gene Expression Regulation - drug effects; Humans; Intercellular Adhesion Molecule-1 - drug effects; Intercellular Adhesion Molecule-1 - metabolism; Interferon-gamma - pharmacology; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - metabolism; Medical sciences; Molecular Sequence Data; Pneumology; Polymerase Chain Reaction; Recombinant Proteins; Respiratory system : syndromes and miscellaneous diseases; RNA, Messenger - analysis; RNA-Directed DNA Polymerase; Transcription, Genetic; Human; Polymerase chain reaction; Flow cytometry; Lung disease; Respiratory disease; Pulmonary alveolus; Reverse transcription; Exploration; Models; Molecular biology; In vitro; Macrophage
• DOI: 10.1183/09031936.96.09030463
• EISSN: 1399-3003
• ISSN: 0903-1936

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.