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Use of a mouse model to evaluate pulmonary inflammation caused by floor dust from a water-damaged building.

Young-S; Cox-Ganser-JM; Wolfarth-M; Antonini-JM; Castranova-V; Park-J
Toxicologist 2008 Mar; 102(1):223
Although the causes of building-related respiratory illness are still unclear, epidemiological research has indicated that fungi and endotoxin in floor dust are associated with such health risks. In the present study, we used a mouse model to evaluate pulmonary inflammation caused by floor dusts collected from the workstations of employees in a water-damaged office building. The dusts were tested in an endotoxin-sensitive strain of mouse - C3HeB/FeJ, and pulmonary inflammation was determined. We examined correlation among markers of inflammation and levels of endotoxin and (1-->3)-beta-D-glucan. Each mouse was treated with dust sample (2.5 mg/kg of body weight suspended in 40 muL of saline) by pharyngeal aspiration. Control mice received an equivalent volume of saline by aspiration. At 18 hrs after aspiration, bronchoalveolar lavage was done postmortem on lungs and the following inflammatory and lung injury markers were measured: (1) neutrophil infiltration, (2) albumin and lactate dehydrogenase levels, and (3) inflammatory cytokines levels. The results demonstrated significant dust-induced inflammation in mice. Significant positive correlations were found between endotoxin levels and IL-6 (r=0.30, p<0.05), IFN-y (r=0.47, p<0.05) and MCP-1 (r=0.33, p<0.05). However, most inflammatory markers showed no correlation with extractable-glucan levels, except for albumin which had a negative correlation. This may be due to the fact that fractions of (1-->3)-beta-D-glucans which induced inflammation are generally not water soluble, but the commercially available analytical method can only measure the water extractable glucan in the dust. Alternative indicators of fungi, such as culturable fungi, may exhibit a better correlation with pulmonary inflammatory potential of floor dusts. Additional studies are ongoing using this animal model with the endotoxin-insensitive strain of mouse (C3H/HeJ) to further examine such correlations.
Lung; Lung-cells; Lung-disease; Lung-disorders; Lung-irritants; Inhalation-studies; Pulmonary-disorders; Pulmonary-system-disorders; Laboratory-animals; Endotoxins; Epidemiology; Dust-analysis; Dust-exposure; Dust-inhalation; Dust-particles; Dust-measurement; Microorganisms
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The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington