Abstract
BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), a sensitization to A. fumigatus has been related to a decline in lung function, but the role of fungal agents in the disease pathogenesis remains unclear. The main purpose of the present study was to investigate whether cell inflammation could worsen after exposure to A. fumigatus spores in vitro and then, in mice, following chronic exposure to cigarette smoke mimicking COPD. METHODS: The inflammatory response to cigarette smoke alone or with A. fumigatus was investigated in cell culture models of murine macrophages and alveolar epithelial cells. In an animal model, mice were exposed daily to two cigarettes smoke over 14 weeks, and two intranasal instillations of 10(5) spores at weeks 7 and 14. Then, their lungs were recovered to perform inflammatory and histopathological analyses. RESULTS: In co-cultures of macrophages and epithelial cells treated with both cigarette smoke extracts (CSE) and A. fumigatus compared to CSE alone there were significant inductions in TNF-α (6.2-fold) and CXCL-2 (21.5-fold) gene expression, confirmed by significant increases in the corresponding protein secretion. In the murine model, histological analyses of the lung after chronic smoke exposure showed an increase in airspace enlargement. Moreover, a Bio-Plex approach on bronchoalveolar lavage of cigarette smoke and A. fumigatus-treated mice showed significant increases in multiple inflammatory proteins secreted in the lung. CONCLUSIONS: There was a stronger inflammatory response after cigarette smoke exposure with A. fumigatus compared to cigarette smoke alone. These findings were correlated with histopathological changes in the mouse lung in vivo.