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

Respirology. 2012 Jul;17(5):802-7. doi: 10.1111/j.1440-1843.2012.02135.x.

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.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / pharmacology*
  • Apoptosis
  • Azithromycin / pharmacology*
  • Bronchoalveolar Lavage
  • Bronchoscopy
  • Dose-Response Relationship, Drug
  • Escherichia coli*
  • Female
  • Fluorescein
  • Humans
  • Longitudinal Studies
  • Macrophages / drug effects
  • Macrophages / pathology*
  • Macrophages / physiology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / pathology*
  • Macrophages, Alveolar / physiology
  • Male
  • Middle Aged
  • Necrosis
  • Phagocytosis / drug effects*
  • Phagocytosis / physiology
  • Pulmonary Disease, Chronic Obstructive / pathology*
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Azithromycin
  • Fluorescein