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SUBCHRONIC ENDOTOXIN INHALATION CAUSES CHRONIC AIRWAY DISEASE IN ENDOTOXIN-SENSITIVE BUT NOT ENDOTOXIN-RESISTANT MICE
Citation:
Brass, D. M., J. D. Savov, S H. Gavett, C. George, AND D. A. Schwartz. SUBCHRONIC ENDOTOXIN INHALATION CAUSES CHRONIC AIRWAY DISEASE IN ENDOTOXIN-SENSITIVE BUT NOT ENDOTOXIN-RESISTANT MICE. Presented at American Thoracic Society, Atlanta, GA, May 17-22, 2002.
Description:
SUBCHRONIC ENDOTOXIN INHALATION CAUSES CHRONIC AIRWAY DISEASE IN ENDOTOXIN-SENSITIVE BUT NOT ENDOTOXIN-RESISTANT MICE. D. M. Brass, J. D. Savov, *S. H. Gavett, ?C. George, D. A. Schwartz. Duke Univ Medical Center Durham, NC, *U.S. E.P.A. Research Triangle Park, NC, ?Univ of Iowa, IA.
To examine the role of endotoxin in grain-dust induced airway disease, we exposed endotoxin sensitive (C3HeB/FeJ) and endotoxin-resistant (C3H/HeJ) mice to an aerosol of endotoxin for 8 weeks followed by a recovery period of 4 weeks. Control animals were treated for the same exposure and recovery period with an aerosol of PBS alone. Airway responsiveness was measured after the 8-week challenge period and again after the 4-week recovery period using whole body plethysmography. Only C3HeB/FeJ mice exhibited significantly elevated airway reactivity in response to methacholine challenge subsequent to the 8-week exposure period. By the end of the 4-week recovery period these values were no longer elevated in C3HeB/FeJ mice. Differential counts of whole lung lavage cells indicate that four days after the last day of endotoxin exposure, the exposed C3HeB/FeJ mice had significantly elevated concentrations of macrophages when compared to exposed C3H/HeJ mice and control C3HeB/FeJ mice. By the end of the 4-week recovery period there was no difference in cell concentrations between the strains or between exposed and control animals. Preliminary analysis by stereology indicates that the submucosa of medium and large airways in C3HeB/FeJ mice are significantly enlarged compared to those of C3H/HeJ mice. Taken together these data indicate that subchronic endotoxin inhalation challenge results in the development of chronic airway disease in mice and these changes are characterized by airway hyperreactivity, reversible airway inflammation, and airway remodeling. (This abstract does not reflect EPA policy).
ES07498 and ES09607