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

• Published in: American journal of respiratory and critical care medicine Vol. 178; no. 2; pp. 139 - 148
• Main Authors: Hodge, Sandra, Hodge, Greg, Jersmann, Hubertus, Matthews, Geoffrey, Ahern, Jessica, Holmes, Mark, Reynolds, Paul N
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 15.07.2008; American Lung Association; American Thoracic Society
• Subjects: Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; 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; Biological and medical sciences; Bronchoalveolar Lavage Fluid - cytology; Case-Control Studies; Cells, Cultured; Chronic obstructive pulmonary disease, asthma; Collectins - drug effects; Collectins - metabolism; Female; Humans; Inflammation; Intensive care medicine; Lectins, C-Type - drug effects; Lectins, C-Type - metabolism; Macrophages, Alveolar - drug effects; Male; Mannose-Binding Lectins - drug effects; Mannose-Binding Lectins - metabolism; Medical sciences; Middle Aged; Phagocytosis - drug effects; Pneumology; Pulmonary Disease, Chronic Obstructive - drug therapy; Receptors, Cell Surface - drug effects; Receptors, Cell Surface - metabolism; Respiratory Mucosa - drug effects; Respiratory Mucosa - metabolism; Statistics, Nonparametric; Lung disease; Intensive care; alveolar macrophage; Respiratory disease; Azithromycin; Mannose; Macrolide; Antibiotic; Bronchus disease; Chronic obstructive pulmonary disease; Protein synthesis inhibitor; Antibacterial agent; Phagocytosis; Resuscitation; Apoptosis; Macrophage
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.200711-1666OC

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. 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. 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. 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. Our findings indicate a novel approach to supplement existing therapies in COPD.