Effects of endotoxin on expression of VLA integrins by human bronchoalveolar lavage macrophages.
Endotoxin (lipopolysaccharide, LPS) is known to induce inflammatory responses, such as monocyte/macrophage adherence, migration, and accumulation. Recruitment and accumulation of macrophages during infection and inflammation are regulated by integrin-mediated cell-extracellular matrix interactions. In the present report, we studied the effects of LPS on the expression of VLA-5 (alpha 5 beta 1), VLA-3 (alpha 3 beta 1), and VLA-2 (alpha 2 beta 1) integrins and fibronectin (FN) by human alveolar macrophages in an attempt to understand the mechanism by which LPS regulates macrophage adhesion to matrix proteins. Bronchoalveolar 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 microscopy, autoradiography, and radioimmunoassay. Immunofluorescent and immunoelectron microscopic observations showed that VLA integrins were constitutively expressed on the cell surface and concentrated on the microvilli and pseudopodia of the macrophages. The effects of LPS on expression 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 pattern. LPS also caused dose-related decreases in the expression of VLA-3 and VLA-2 integrins and increases of intracellular FN 24 h after stimulation. The results suggest that a prolonged exposure to LPS may impede VLA integrin-mediated migration and result in local accumulation of macrophages in the lung.
Kang
Y H
YH
Septic Shock Research Program, Naval Medical Research Institute, Bethesda, MD 20889-5607, USA.
Lee
C H
CH
Brummel
S E
SE
Newball
H H
HH
Forrester
J
J
D001345:Autoradiography; D001992:Bronchoalveolar Lavage Fluid; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D005353:Fibronectins / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D011863:Radioimmunoassay; D015854:Up-Regulation / Q000187:drug effects
D005353:Fibronectins; D016023:Integrins; D008070:Lipopolysaccharides