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

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.

• Authors: Sandra Hodge, Greg Hodge, Hubertus Jersmann, Geoffrey Matthews, Jessica Ahern, Mark Holmes, Paul N Reynolds
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 178 Issue 2 Pg. 139-48 (Jul 15 2008) ISSN: 1535-4970 [Electronic] United States
• PMID: 18420960 (Publication Type: Clinical Trial, Journal Article)

Chemical References

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

Topics

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