Azithromycin increases phagocytosis of apoptotic bronchial epithelial cells by alveolar macrophages

¹ Dept of Thoracic Medicine, Royal Adelaide Hospital and Lung Research Laboratory, Hanson Institute, Adelaide, South Australia

^* To whom correspondence should be addressed. E-mail: sandy.hodge{at}imvs.sa.gov.au.

	Abstract

Chronic obstructive pulmonary disease (COPD) is associated with increased apoptosis and defective phagocytosis in the airway. As uncleared cells can undergo secondary necrosis and perpetuate inflammation, strategies to improve clearance would have therapeutic significance. There is evidence that the 15-member macrolide antibiotic azithromycin has anti-inflammatory properties. Its effects may be increased in the lung due to its ability to reach high concentrations in alveolar macrophages (AM).

This study investigated the effects of low-dose (500 ng·ml^-1) azithromycin on phagocytosis of apoptotic bronchial epithelial cells and neutrophils by AM.

Flow cytometry was applied to measure phagocytosis and receptors involved in AM recognition of apoptotic cells. Cytokines were investigated using cytometric bead array.

Baseline phagocytosis was reduced in COPD subjects compared to controls. Azithromycin significantly improved the phagocytosis of epithelial cells or neutrophils by AM from COPD subjects by 68% and 38% respectively, often up to levels comparable to controls. The increase in phagocytosis was partially inhibited by phosphatidylserine (PS), implicating the PS pathway in the pro-phagocytic effects of azithromycin. Azithromycin had no effect on other recognition molecules (GM-CSF, CD44, CD31, CD36, CD91, v3integrin). At higher doses azithromycin decreased levels of pro-inflammatory cytokines. Low-dose azithromycin therapy could thus provide an adjunct therapeutic option in COPD.

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