Expression of leucocyte–endothelial adhesion molecules is limited to intercellular adhesion molecule-1 (ICAM-1) in the lung of pneumoconiotic patients: role of tumour necrosis factor-alpha (TNF-α)

Coal workers' pneumoconiosis (CWP) is characterized by a chronic inflammatory lung reaction associated with macrophage accumulation in alveolar spaces. In this study, we investigated in CWP the implication of adhesion molecules such as E-selectin, ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) and the role of TNF-α which is one of the cytokines inducing their expression. Adhesion molecule expression was analysed by immunohistochemistry on lung biopsies from patients with CWP and from healthy subjects. In parallel, soluble adhesion molecules were detected in bronchoalveolar lavage fluids (BALF) from patients by specific ELISA. The involvement of TNF in the induction of these adhesion molecules was measured (i) by immunohistochemistry on sections from lung fragments, and (ii) by evaluating in vitro the expression of adhesion molecules on endothelial cells and on alveolar epithelial cells in the presence of alveolar macrophage supernatants. In control subjects, a weak staining of ICAM-1 was detected only in alveolar walls, while E-selectin and VCAM-1 were undetectable. In pneumoconiotic patients, ICAM-1 was expressed at a high level by endothelium, by alveolar and bronchial epithelial cells and by alveolar macrophages. E-selectin and VCAM-1 expression remained undetectable. Measurement of soluble adhesion molecule showed that only the concentration of sICAM-1 was significantly increased in BALF from patients with CWP compared with controls. The involvement of TNF in this ICAM-1 expression was shown by the in vitro effect of alveolar macrophage supernatants on adhesion molecule expresssion by endothelial cells and epithelial cells (this effect was neutralized by anti-TNF antibodies) and by the increased production of TNF in the lung of pneumoconiotic patients. These data provide evidence for the involvement of ICAM-1, induced at least in part by alveolar macrophage-derived TNF, in the development of the inflammatory reaction in CWP.