title: Low-dose azithromycin improves phagocytosis of bacteria by both alveolar and monocyte-derived macrophages in chronic obstructive pulmonary disease subjects.
abstract: 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.
authors.affiliation: Lung Research Laboratory, Hanson Institute Department of Thoracic Medicine, Royal Adelaide Hospital, University of Adelaide, Adelaide, South Australia, Australia. sandra.hodge@health.sa.gov.au
authors.forename: Sandra
authors.initials: S
authors.lastname: Hodge
authors.forename: Paul N
authors.initials: PN
authors.lastname: Reynolds
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis; D017963:Azithromycin / Q000494:pharmacology*; D018893:Bronchoalveolar Lavage; D001999:Bronchoscopy; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D005260:Female; D019793:Fluorescein; D006801:Humans; D008137:Longitudinal Studies; D008264:Macrophages / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D010587:Phagocytosis / Q000187:drug effects* / Q000502:physiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin; D019793:Fluorescein