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Low-dose azithromycin improves phagocytosis of bacteria by both alveolar and monocyte-derived macrophagesin chronic obstructive pulmonary disease subjects

Authors

  • SANDRA HODGE,

    Corresponding author
    1. Lung Research Laboratory, Hanson Institute
    2. Department of Thoracic Medicine, Royal Adelaide Hospital
    3. Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia
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  • PAUL N. REYNOLDS

    1. Lung Research Laboratory, Hanson Institute
    2. Department of Thoracic Medicine, Royal Adelaide Hospital
    3. Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia
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Sandra Hodge, Lung Research, Hanson Institute, Frome Road, Adelaide, SA 5001, Australia. Email: sandra.hodge@health.sa.gov.au

ABSTRACT

Background and objective:  Chronic inflammation and reduced airways integrity in chronic obstructive pulmonary disease (COPD) potentially results from secondary necrosis as a result of impaired phagocytosis of apoptotic material by airway macrophages, and increased bacterial colonization. We have previously shown that administration of low-dose azithromycin to subjects with COPD improved macrophage phagocytosis of apoptotic airway epithelial cells, reduced inflammation and increased expression of macrophage mannose receptor.

Methods:  We firstly investigated whether there were defects in the ability of both alveolar (AM) and monocyte-derived macrophages (MDM) to phagocytose bacteria in COPD, as we have previously reported for phagocytosis of apoptotic cells. We then assessed the effects of administration of low-dose azithromycin to COPD patients on the ability of AM and MDM to phagocytose bacteria. Azithromycin (250 mg orally daily for 5 days then 2× weekly (total 12 weeks)) was administered to 11 COPD subjects and phagocytosis of fluorescein isothiocyanate-labelled Escherichia coli assessed by flow cytometry.

Results:  COPD subjects had a significant defect in the ability of both AM and MDM to phagocytose bacteria that was significantly improved by administration of low-dose azithromycin

Conclusions:  The data provide further support for the long-term use of low dose azithromycin as an attractive adjunct treatment option for COPD. Improved clearance of both apoptotic cells and bacteria in the airway may have a dual effect; reducing the risk of secondary necrosis and release of toxic cell contents that perpetuate inflammation as well as contributing to a reduction in the rate of exacerbations in COPD.

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