Silica induces lung inflammation, type II cell hyperplasia and altered lung mechanics in mice.
Joseph-LB; Laskin-D; Cervelli-J; Elzind-DA; Zeidler-Erdely-P; Gow-AJ; Laskin-JD; Castranova-V
Toxicologist 2009 Mar; 108(1):390
Epidemiologic studies have demonstrated that chronic exposure to crystalline silica (quartz) leads to the development of small airway disease and decreased airflow. We speculate that early release of inflammatory mediators contributes to this process. To test this, we examined the effects of exposure of mice to silica on pulmonary inflammation and lung function. C57bl/6J mice were treated intratracheally with silica (1 mg/kg Min-U-Sil 5) or PBS control. Mice were sacrificed seven days later. Total protein and cell content in bronchoalveolar fluid (BALF) increased 2-fold following silica treatment. The cellular infiltrate consisted of neutrophils and macrophages. Both "free silica" and silica engorged macrophages were also observed in BALF. We also found that expression of cyclooxygenase-2 (COX-2), a key enzyme in eicosanoid production, and surfactant protein-D (SP-D), a collectin important in regulating lung inflammation, were upregulated in the lung following silica exposure. Proliferating cell nuclear antigen (PCNA) was also upregulated in the alveolar epithelium following silica exposure. This was correlated with increased expression of the Type II cell marker, proSP-C, suggesting that silica induces Type II cell hyperplasia. In further studies we assessed the effects of silica exposure on lung function by measuring lung responsiveness to inhaled methacholine using a SCIREQ flexiVent. In both control and silica treated mice, quasi-static compliance (Cst), which reflects the elastic static recoil pressure at the level of the alveoli, decreased upon challenge with methacholine. These effects were significantly greater in animals exposed to silica suggesting a greater loss in lung elasticity. Taken together, these data suggest that early inflammatory changes may be important in structural and functional changes in the lung induced following exposure to silica.
Antigens; Biological-effects; Biological-factors; Cell-function; Cell-metabolism; Cellular-function; Cellular-reactions; Epidemiology; Exposure-assessment; Exposure-levels; Exposure-methods; Irritants; Laboratory-animals; Lung-cells; Lung-disorders; Lung-irritants; Microscopic-analysis; Microscopy; Particle-aerodynamics; Particulate-dust; Particulates; Pulmonary-disorders; Pulmonary-system; Pulmonary-system-disorders; Respiratory-irritants; Respiratory-system-disorders; Statistical-analysis
The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland