Role of ICAM-1 in the aggregation and adhesion of human alveolar macrophages in response to TNF-a and INF-g

CA Corresponding Author Tel: +81 18 884 6107 Fax: +81 18 836 2612 E-mail: masahiro@im2.med.akita-u.ac.jp IN TRAC ELLUL AR adhesion molecule-1 (ICAM-1)-mediated cellÐcell adhesion is thought to play an important role at sites of inflammation. Recent evidence suggests that ICAM-1 surface expression on alveolar macrophages is increased in pulmonary sarcoidosis and that inflammatory granuloma formation is characterized by the aggregation of macrophages. The present study shows that ICAM-1 expression is significantly elevated on alveolar macrophages from patients with sarcoidosis in response to tumor necrosis factora (TNFa ) and interferon-g (INFg ) compared with healthy controls. Aggregation and adhesion were significantly increased in alveolar macrophages treated with TNFa and INFg , and significantly inhibited in those pretreated with a monoclonal antibody to ICAM-1. Similarly, aggregation and adhesion were inhibited in macrophages treated with heparin, which then exhibited a wide range of biological activities relevant to inflammation. These results suggested that the surface expression of ICAM-1 on alveolar macrophages in response to TNFa and INFg is important in mediating aggregation and adhesion. Additionally, heparin may be useful for developing novel therapeutic agents for fibrotic lung disease.