EFFECTS OF ENDOTOXIN ON EXPRESSION OF VLA INTEGRINS BY HUMAN BRONCHOALVEOLAR LAVAGE MACROPHAGES

Endotoxin (lipopolysaccharide, LPS) is known to induce inflammatory re sponses, such as monocyte/macrophage adherence, migration, and accumul ation. Recruitment and accumulation of macrophages during infection an d inflammation are regulated by integrin-mediated cell-extracellular m atrix interactions. In the present report, we studied the effects of L PS on the expression of VLA-5 (alpha(5) beta(1)), VLA-3 (alpha(3) beta (1)), and VLA-5 (alpha(2) beta(1)) integrins and fibronectin (FN) by h uman alveolar macrophages in an attempt to understand the mechanism by which LPS regulates macrophage adhesion to matrix proteins. Bronchoal veolar lavage macrophages were treated with varying concentrations of Escherichia coli LPS for different times and evaluated for expression of the integrins and FN by immunofluorescence, immunoelectron microsco py, autoradiography, and radioimmunoassay. Immunofluorescent and immun oelectron microscopic observations showed that VLA integrins were cons titutively expressed on the cell surface and concentrated on the micro villi and pseudopodia of the macrophages. The effects of LPS on expres sion of the integrins were dose and time related. VLA-5 expression was increased after 30 min of stimulation by LPS, suggesting that LPS may induce rapid secretion of the integrin. However, incubations with LPS longer than 30 min decreased VLA-5 expression in a dose-dependent pat tern. LPS also caused dose-related decreases in the expression of VLA- 3 and VLA-2 integrins and increases of intracellular FN 24 h after sti mulation. The results suggest that a prolonged exposure to LPS may imp ede VLA integrin-mediated migration and result in local accumulation o f macrophages in the lung.