title: Azithromycin improves macrophage phagocytic function and expression of mannose receptor in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Defective efferocytosis (phagocytic clearance of apoptotic cells) in the airway may perpetuate inflammation via secondary necrosis in chronic obstructive pulmonary disease (COPD). We have previously reported that low-dose azithromycin improved alveolar macrophage (AM) phagocytic function in vitro.
  
  
  OBJECTIVE
  We investigated collectins (mannose-binding lectin [MBL] and surfactant protein [SP]-D) and mannose receptor (MR) in COPD and their possible role in the azithromycin-mediated improvement in phagocytosis.
  
  
  METHODS
  In vitro effects of azithromycin on AM expression of MR were investigated. MBL, SP-D, and MR were measured in patients with COPD and control subjects. Azithromycin (250 mg orally daily for 5 d then twice weekly for 12 wk) was administered to 11 patients with COPD. Assessments included AM phagocytic ability and expression of MR, MBL, SP-D, bronchial epithelial cell apoptosis, pulmonary function, C-reactive protein, blood/BAL leukocyte counts, cytokine production, and T-cell markers of activation and phenotype.
  
  
  RESULTS
  Azithomycin (500 ng/ml) increased MR expression by 50% in vitro. AM MR expression and levels of MBL and SP-D were significantly reduced in patients with COPD compared with control subjects. In patients with COPD, after azithromycin therapy, we observed significantly improved AM phagocytic ability (pre: 9.9%; post: 15.1%), reduced bronchial epithelial cell apoptosis (pre: 30.0%; post: 19.7%), and increased MR and reduced inflammatory markers in the peripheral blood. These findings implicate the MR in the defective phagocytic function of AMs in COPD and as a target for the azithromycin-mediated improvement in phagocytic ability.
  
  
  CONCLUSIONS
  Our findings indicate a novel approach to supplement existing therapies in COPD.
authors.affiliation: Department of Thoracic Medicine, Royal Adelaide Hospital and Lung Research Laboratory, Hanson Institute, Adelaide, South Australia, Australia. sandy.hodge@imvs.sa.gov.au
authors.forename: Sandra
authors.initials: S
authors.lastname: Hodge
authors.forename: Greg
authors.initials: G
authors.lastname: Hodge
authors.forename: Hubertus
authors.initials: H
authors.lastname: Jersmann
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Matthews
authors.forename: Jessica
authors.initials: J
authors.lastname: Ahern
authors.forename: Mark
authors.initials: M
authors.lastname: Holmes
authors.forename: Paul N
authors.initials: PN
authors.lastname: Reynolds
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D017963:Azithromycin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016022:Case-Control Studies; D002478:Cells, Cultured; D037222:Collectins / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation; D037181:Lectins, C-Type / Q000187:drug effects* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D010587:Phagocytosis / Q000187:drug effects*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D000900:Anti-Bacterial Agents; D037222:Collectins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D017963:Azithromycin