Role of ICAM-1 in the aggregation and adhesion of human alveolar macrophages in response to TNF-alpha and INF-gamma.
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-alpha (TNF-alpha) and interferon-gamma (INF-gamma) compared with healthy controls. Aggregation and adhesion were significantly increased in alveolar macrophages treated with TNF-alpha and INF-gamma, 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-alpha and INF-gamma is important in mediating aggregation and adhesion. Additionally, heparin may be useful for developing novel therapeutic agents for fibrotic lung disease.
Sasaki
M
M
Second Department of Internal Medicine, Akita University School of Medicine, Hondo, Japan. masahiro@im2.med.akita-u.ac.jp
Namioka
Y
Y
Ito
T
T
Izumiyama
N
N
Fukui
S
S
Watanabe
A
A
Kashima
M
M
Sano
M
M
Shioya
T
T
Miura
M
M
D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002449:Cell Aggregation / Q000187:drug effects / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D007958:Leukocyte Count; D016676:Macrophages, Alveolar / Q000166:cytology* / Q000378:metabolism; D008297:Male; D017565:Sarcoidosis, Pulmonary / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000925:Anticoagulants; D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D006493:Heparin