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Establishing a Silicosis Rat Model via Exposure of Whole-Body to Respirable Silica
Published on: October 28, 2022
Localization of intercellular adhesion molecule-1 (ICAM-1) in the lungs of silica-exposed mice
1Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs 06269, USA.
Insights
Silica particle exposure significantly increases intercellular adhesion molecule-1 (ICAM-1) in lung macrophages and epithelial cells, contributing to pulmonary inflammation. Titanium dioxide dust showed minimal effects on ICAM-1 expression.
Area of Science:
- Pulmonary toxicology
- Immunology
- Cell biology
Background:
- Intercellular adhesion molecule-1 (ICAM-1) is crucial for leukocyte migration during pulmonary inflammation.
- Previous studies indicated elevated ICAM-1 in silica-induced lung inflammation, implicating it in neutrophil migration.
Purpose of the Study:
- To investigate the localization and temporal expression of ICAM-1 in mouse lungs following exposure to silica or titanium dioxide particles.
- To correlate ICAM-1 expression with inflammatory markers like tumor necrosis factor alpha.
Main Methods:
- Intratracheal instillation of silica or titanium dioxide particles in mice.
- Immunohistochemistry to localize ICAM-1 and tumor necrosis factor alpha expression in lung tissue.
- Immunocytochemistry to assess ICAM-1 on bronchoalveolar lavage (BAL) cells.
- Measurement of soluble ICAM-1 levels in BAL fluid.
Main Results:
- Silica exposure significantly increased ICAM-1 on pulmonary macrophages and type II epithelial cells by day 1.
- Increased ICAM-1 expression correlated with elevated tumor necrosis factor alpha.
- ICAM-1 was upregulated on alveolar macrophages in BAL fluid from day 3 to 7 post-silica exposure.
- Soluble ICAM-1 levels in BAL fluid were significantly increased after silica exposure.
- Titanium dioxide exposure resulted in minimal ICAM-1 upregulation.
Conclusions:
- Silica particles, but not titanium dioxide, specifically induce ICAM-1 expression in pulmonary macrophages and type II epithelial cells.
- The upregulation of ICAM-1 is a key feature of silica-induced pulmonary inflammation.
Abstract:
Intercellular adhesion molecule-1 (ICAM-1) is expressed on a variety of cells including endothelial cells, alveolar epithelial cells, and alveolar 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 activation. Our previous studies have shown that there is increased expression of ICAM-1 in lung tissue during acute inflammation following intratracheal injection with silica particles (2 mg/mouse). This increased expression was shown to play a role, in part, in the migration of neutrophils from the circulation into the tissue parenchyma. The aim of the current work is to localize expression of ICAM-1 during acute inflammation in lungs of mice exposed to either silica or the nuisance dust, 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 increased tumor necrosis factor alpha expression. Immunocytochemical staining of bronchoalveolar lavage (BAL) cells demonstrated increased ICAM-1 expression associated with alveolar macrophages 3, 5, and 7 days following silica exposure. Finally, soluble ICAM-1 levels in the BAL fluid were significantly increased in mice exposed to silica on the same days. Titanium dioxide exposure elicited a minimal increase in expression of ICAM-1 in the lungs. These data demonstrate that exposure to the toxic particle silica specifically increases ICAM-1 expression localized to pulmonary macrophages and type II epithelial cells.
