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Type: Journal article
Title: Azithromycin increases phagocytosis of apoptotic bronchial epithelial cells by alveolar macrophages
Author: Hodge, S.
Hodge, G.
Brozyna, S.
Jersmann, H.
Holmes, M.
Reynolds, P.
Citation: European Respiratory Journal, 2006; 28(3):486-495
Publisher: European Respiratory Soc Journals Ltd
Issue Date: 2006
ISSN: 0903-1936
Statement of
S. Hodge, G. Hodge, S. Brozyna, H. Jersmann, M. Holmes, and P. N. Reynolds
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 (AMs). The present study investigated the effects of low-dose (500 ng·mL-1) azithromycin on the phagocytosis of apoptotic bronchial epithelial cells and neutrophils by AMs. 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 with controls. Azithromycin significantly improved the phagocytosis of epithelial cells or neutrophils by AMs from COPD subjects by 68 and 38%, respectively, often up to levels comparable with controls. The increase in phagocytosis was partially inhibited by phosphatidylserine, implicating the phosphatidylserine pathway in the pro-phagocytic effects of azithromycin. Azithromycin had no effect on other recognition molecules (granulocyte-macrophage colony-stimulating factor, CD44, CD31, CD36, CD91, vß3 integrin). At higher doses, azithromycin decreased levels of pro-inflammatory cytokines. Thus, low-dose azithromycin therapy could provide an adjunct therapeutic option in chronic obstructive pulmonary disease.
Keywords: alveolar macrophage; apoptosis; azithromycin; chronic obstructive pulmonary disease; phagocytosis
Rights: © ERS Journals Ltd 2006
RMID: 0020061248
DOI: 10.1183/09031936.06.00001506
Appears in Collections:Medicine publications

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