Exposure to silica increases intercellular adhesion molecule-1 in mice

Date of Completion

January 1997


Health Sciences, Occupational Health and Safety|Health Sciences, Toxicology|Health Sciences, Immunology




Silica inhalation by humans is a health hazard in occupations such as coal mining, quarrying, and sand blasting. Chronic exposure by these individuals to silica may result in pulmonary fibrosis and impaired lung function. Several animal models have examined the initial inflammatory response from silica exposure to understand the progression of early disease to fibrosis. These works demonstrate a significant neutrophil influx into the bronchoalveolar space within one day of exposure followed by an influx of macrophages. It is unclear if this leukocyte migration is dependent upon the increased expression of adhesion proteins.^ This "adhesion cascade" is a complex process involving the upregulation and downregulation of several membrane bound proteins on the leukocyte cell surface and on the cells with which they interact. This research examines the expression and role of one adhesion molecule, intercellular adhesion molecule-1 (ICAM-1), during the inflammatory response elicited by silica exposure.^ In silica exposed mice, a significant increase in ICAM-1 in lung tissue was observed one day after exposure. This expression was localized by immunohistochemistry to focal areas adjacent to large airways with detection on alveolar type II epithelial cells and lung macrophages (interstitial and alveolar). Expression of ICAM-1 on alveolar macrophages was later confirmed by immunocytochemical analysis of cells isolated by bronchoalveolar lavage. Analysis of the lavage fluid from silica exposed mice also showed significant increases in soluble ICAM-1 levels. These increases in cell-associated ICAM-1 and sICAM-1 were specific to the toxic particle silica; the nuisance dust titanium dioxide elicited only a minimal increase in ICAM-1.^ We have documented that increased ICAM-1 expression plays a partial role in neutrophil extravasation into the lungs. Passive immunization with an anti-ICAM-1 antibody significantly reduced the neutrophil influx observed one day after silica exposure. However, neither this antibody nor the reduced numbers of neutrophils resulted in a decrease in acute or chronic lung injury. Finally, silica induced ICAM-1 expression may be a consequence of the cytokine tumor necrosis factor-$\alpha$ (TNF$\alpha).$ TNF$\alpha$ and ICAM-1 were co-localized to the same histopathological areas in lungs from silica exposed mice and ICAM-1 expression on cultured alveolar macrophages was reduced by anti-TNF$\alpha$ antibody. ^