Cellular and molecular mechanisms regulating silica-induced adhesion molecule expression in mice.
Exposure of mice to silica particles generates an intense inflammatory response characterized by the influx of neutrophils and monocytes into the alveoli with resulting cell activation. These cell trafficking and effector functions are, in part, mediated by different families of adhesion molecules. One such adhesion protein, intercellular adhesion molecule-1 (ICAM-1), is expressed on a variety of cells including vascular endothelial cells, fibroblasts, types I and II alveolar epithelial cells, some lymphocytes, and monocytes/macrophages. Over the last several years, our laboratory has focused on silica-induced ICAM-1 expression in exposed mice (in vivo) and cells (in vitro) by examining the role and regulation of this adhesion protein on pulmonary cells. We have determined that intratracheal exposure of mice to silica (2 mg per mouse) elicits increased expression of ICAM-1 on pulmonary macrophages and type II epithelial cells within the lung parenchyma, on bronchoalveolar lavage macrophages, and as a soluble protein in lavage fluid. We hypothesize that increased ICAM-1 expression mayparticipate in silica-induced neutrophil influx into the alveoli, as well as in macrophage-derived phlogistic signals responsible for migration of neutrophils. ICAM-1 expression on silica-exposed mouse macrophages is enhanced by reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-alpha) and appears to be regulated through specific sequence elements within the ICAM-1 promoter.
Hubbard
A K
AK
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, USA. hubbard@uconnvm.uconn.edu
Thibodeau
M
M
Giardina
C
C
D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007249:Inflammation / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008168:Lung / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology*; D012822:Silicon Dioxide / Q000633:toxicity*
D000395:Air Pollutants, Occupational; D018799:Intercellular Adhesion Molecule-1; D012822:Silicon Dioxide