MODULATION OF ENDOTHELIAL-CELL ADHESION MOLECULE EXPRESSION IN A SITUATION OF CHRONIC INFLAMMATORY STIMULATION

Different disorders affecting the respiratory tract are characterized by the development of a chronic inflammatory reaction with an accumulation of immune and inflammatory cells into the bronchial walls and in interstitial and alveolar spaces. By its ability to secrete a large panel of cytokines, in particular TNF-alpha, the alveolar macrophage (AM) is undoubtedly playing a key role in the complex interactions between inflammatory and structural cells potentially implicated in the inflammatory reaction of the lung. One aspect of these interactions is the capacity of AM-derived TNF-alpha to induce the expression of cellular adhesion molecules (CAM) on the surface of endothelial cells. The main information concerning the induction of CAM have been obtained under experimental conditions mimicking an acute inflammatory reaction. In the present study, we propose an in vitro model allowing the reproduction of the conditions of a chronic inflammation, namely, the endothelial cell behavior submitted to a chronic TNF-alpha stimulation. The endothelial cell activation parameters were the modulation of expression of adhesion molecules: endothelial-leukocyte adhesion molecule-1 (E-selectin), intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1). Their functional abilities was evaluated using U937 cell adhesion analysis. Results demonstrated an overexpression of ICAM-1 after chronic stimulation performed with low but repeated doses of TNF-alpha. The level of ICAM-1 expression persisted throughout the culture to reach a high stable level despite the absence of detectable TNF-alpha activity in culture supernatants. If the stimulation was stopped after 6 days, the expression of ICAM-1 was still observed at least until Day 15. E-selectin and VCAM-1 expression remained absent or not significantly increased. The expression of ICAM-1 on endothelial cells was directly related to an enhanced adhesion capacity as demonstrated by the adhesion of U937 cells to endothelial cells by an ICAM-1/LFA-1 adhesion pathway. Taken together, these elements could bring new approaches in the investigation of mechanisms by which inflammatory cells are recruited and participate in chronic inflammatory processes. (C) 1994 Academic Press, Inc.