Isolated alveolar macrophages from mice wit different sensitivity to sigarette smoke react differently when exposed to sigarette smoke

RATIONALE: Cigarette smoke (CS) is one of the main risk factors in COPD, but only 20% of chronic smokers develop the disease. In vivo studies demonstrated that mice of the C57Bl/6J strain are sensitive to CS and develop emphysema, while ICR mice are not. Since macrophages play a central role in the development of COPD, the aim of this study was to verify if the different sensitivity observed in vivo in C57Bl/6J and ICR mice could be also extended to their isolated alveolar cells. METHODS & RESULTS: Alveolar macrophages were isolated from bronchoalveolar lavage fluid and exposed to 3 doses of bubbled CS. LDH release revealed that C57Bl/6J cells were more susceptible to CS toxicity than ICR. The type of cell death (necrosis or apoptosis) was then investigated. Apoptosis was evaluated by immunocitochemistry detection of caspase-3. In C57Bl/6J macrophages the number of apoptotic cells was significantly increased at the lowest CS dose, while at high doses necrosis was more evident. No signs of apoptosis were visible in ICR cells. Clear differences were observed in the cytokine profile between the two strains after CS exposure. The release of MIP-2 by C57Bl/6J cells was significantly increased in respect to ICR cells treated with the same CS dose. A similar trend was observed for KC, a MIP-2 isoform. Additionally, TNF- and IL-6 were increased (12 and 3-fold respectively) in C57Bl/6J vs controls, while these cytokines were not detectable in ICR. Exposure of human U937 promonocytes to CS showed responses very similar to those observed in ICR macrophages. CONCLUSIONS: These results demonstrate a different qualitative and quantitative response to CS by alveolar macrophages from C57Bl/6J and ICR mice, suggesting that the in vivo differences may have an in vitro counterpart. (Supported by Siena University, PAR 2005-2006)