Azithromycin increases phagocytosis of apoptotic airway epithelial cells by alveolar macrophages in vitro

Abstract

COPD and bronchiolitis obliterans syndrome (BOS) are inflammatory airways diseases associated with increased apoptosis of airway epithelial cells1. In addition there is defective clearance of these apoptotic cells by alveolar macrophages (AM) in COPD2. Uncleared cells can undergo secondary necrosis and perpetuate the inflammatory response, thus strategies to improve clearance would have therapeutic significance. The 15-member macrolide antibiotic azothromycin has reported anti-inflammatory properties. These effects may be enhanced in the lung due to its ability to reach high concentrations in AM with sustained concentrations in tissues. We investigated the effects of azithromycin at clinically achievable levels (500-100,000ng/ml) on phagocytosis of apoptotic bronchial epithelial cells by BAL-derived AM, using flow cytometry. Azithromycin significantly improved the clearance of apoptotic cells by AM (mean increase 50%). No changes were noted using a 16-member macrolide, clindamycin. Increasing the dose of azithromycin did not significantly improve the rate of phagocytosis. Azithromycin had no negative effect on viability of AM or epithelial cells after 24h. Antiinflammatory effects of azithromycin on AM were confirmed by a significant decrease in levels of IL-8 and TNF-a in culture supernatant. These findings provide an exciting potential for new therapeutic options for COPD and BOS. 1 S Hodge et al, Eur Respir J 2005;25(3) 2 S Hodge et al, Immunol Cell Biol 2003; 81:289