Azithromycin improves macrophage phagocytic function and expression of mannose receptor in chronic obstructive pulmonary disease

Am J Respir Crit Care Med. 2008 Jul 15;178(2):139-48. doi: 10.1164/rccm.200711-1666OC. Epub 2008 Apr 17.

Abstract

Rationale: 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.

Objectives: 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.

Measurements and main 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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Apoptosis / drug effects
  • Azithromycin / administration & dosage
  • Azithromycin / pharmacology*
  • Azithromycin / therapeutic use
  • Bronchoalveolar Lavage Fluid / cytology
  • Case-Control Studies
  • Cells, Cultured
  • Collectins / drug effects
  • Collectins / metabolism
  • Female
  • Humans
  • Inflammation
  • Lectins, C-Type / drug effects*
  • Lectins, C-Type / metabolism
  • Macrophages, Alveolar / drug effects*
  • Male
  • Mannose-Binding Lectins / drug effects*
  • Mannose-Binding Lectins / metabolism
  • Middle Aged
  • Phagocytosis / drug effects*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Receptors, Cell Surface / drug effects*
  • Receptors, Cell Surface / metabolism
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / metabolism
  • Statistics, Nonparametric

Substances

  • Anti-Bacterial Agents
  • Collectins
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • mannose receptor
  • Azithromycin