Azithromycin improves macrophage phagocytic function and expression of mannose receptor in chronic obstructive pulmonary disease.
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.
Hodge
Sandra
S
Department of Thoracic Medicine, Royal Adelaide Hospital and Lung Research Laboratory, Hanson Institute, Adelaide, South Australia, Australia. sandy.hodge@imvs.sa.gov.au
Hodge
Greg
G
Jersmann
Hubertus
H
Matthews
Geoffrey
G
Ahern
Jessica
J
Holmes
Mark
M
Reynolds
Paul N
PN
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
D000900:Anti-Bacterial Agents; D037222:Collectins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D017963:Azithromycin