Role of ICAM‐1 in the aggregation and adhesion of human alveolar macrophages in response to TNF‐α and INF‐γ

Abstract

Intracellular adhesion molecule‐1 (ICAM‐1)‐mediated cell‐cell 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 factor‐α (TNF‐α) and interferon‐ γ (INF‐γ) compared with healthy controls. Aggregation and adhesion were significantly increased in alveolar macrophages treated with TNF‐α and INF‐γ, 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 TNF‐α and INF‐γ is important in mediating aggregation and adhesion. Additionally, heparin may be useful for developing novel therapeutic agents for fibrotic lung disease.