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Azithromycin Improves Macrophage Phagocytic Function and Expression of Mannose Receptor in Chronic Obstructive Pulmonary Disease

¹ Department of Thoracic Medicine, Royal Adelaide Hospital and Lung Research Laboratory, Hanson Institute, Adelaide, South Australia, Australia; and ² University of Adelaide, Adelaide, South Australia, Australia

Correspondence and requests for reprints should be addressed to Dr. Sandra Hodge, M.Sc. Ph.D., Lung Research, Hanson Institute, Frome Road, Adelaide, South Australia 5001. E-mail: sandy.hodge{at}imvs.sa.gov.au

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.

Key Words: chronic obstructive pulmonary disease • alveolar macrophage • phagocytosis • azithromycin • apoptosis

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Defective phagocytosis in the airway may perpetuate inflammation in chronic obstructive pulmonary disease (COPD). Low-dose azithromycin improves phagocytosis in vitro; however, the mechanisms and the effect of in vivo administration to subjects with COPD have not been determined. What This Study Adds to the Field Our findings of improved macrophage phagocytic ability and reduced systemic inflammation after low-dose azithromycin therapy provide further rationale for investigating macrolides as supplements to existing therapies in COPD.

 

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