LOCALIZATION OF INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) IN THE LUNGS OF SILICA-EXPOSED MICE

Intercellular adhesion molecule-1 (ICAM-1) is expressed on a variety o f cells including endothelial cells, alveolar epithelial cells, and al veolar macrophages. Endothelial/epithelial cell ICAM-1 participates in the migration of leukocytes out of the blood in response to pulmonary inflammation, whereas alveolar macrophage ICAM-1 may represent cell a ctivation. Our previous studies have shown that there is increased exp ression of ICAM-1 in lung tissue during acute inflammation following i ntratracheal injection with silica particles (2 mg/mouse). This increa sed expression was shown to play a role, in part, in the migration of neutrophils from the circulation into the tissue parenchyma. The aim o f the current work is to localize expression of ICAM-1 during acute in flammation in lungs of mice exposed to either silica or the nuisance d ust, titanium dioxide. In silica-exposed mice, a significant increase in ICAM-1 was detected on day 1 and localized by immunohistochemistry to aggregates of pulmonary macrophages and to type ii epithelial cells . Areas of the lung with increased ICAM-1 expression also showed incre ased tumor necrosis factor alpha expression. Immunocytochemical staini ng of bronchoalveolar lavage (BAL) cells demonstrated increased ICAM-1 expression associated with alveolar macrophages 3, 5, and 7 days foll owing silica exposure. Finally, soluble ICAM-1 levels in the BAL fluid were significantly increased in mice exposed to silica on the same da ys. Titanium dioxide exposure elicited a minimal increase in expressio n of ICAM-1 in the lungs. These data demonstrate that exposure to the toxic particle silica specifically increases ICAM-1 expression localiz ed to pulmonary macrophages and type ii epithelial cells.