Low-dose azithromycin improves phagocytosis of bacteria by both alveolar and monocyte-derived macrophages in chronic obstructive pulmonary disease subjects.

Abstract

BACKGROUND AND OBJECTIVE:

Chronic inflammation and reduced airways integrity in chronic obstructive pulmonary disease (COPD) potentially results from secondary necrosis as a result of impaired phagocytosis of apoptotic material by airway macrophages, and increased bacterial colonization. We have previously shown that administration of low-dose azithromycin to subjects with COPD improved macrophage phagocytosis of apoptotic airway epithelial cells, reduced inflammation and increased expression of macrophage mannose receptor.

METHODS:

We firstly investigated whether there were defects in the ability of both alveolar (AM) and monocyte-derived macrophages (MDM) to phagocytose bacteria in COPD, as we have previously reported for phagocytosis of apoptotic cells. We then assessed the effects of administration of low-dose azithromycin to COPD patients on the ability of AM and MDM to phagocytose bacteria. Azithromycin (250 mg orally daily for 5 days then 2× weekly (total 12 weeks)) was administered to 11 COPD subjects and phagocytosis of fluorescein isothiocyanate-labelled Escherichia coli assessed by flow cytometry.

RESULTS:

COPD subjects had a significant defect in the ability of both AM and MDM to phagocytose bacteria that was significantly improved by administration of low-dose azithromycin

CONCLUSIONS:

The data provide further support for the long-term use of low dose azithromycin as an attractive adjunct treatment option for COPD. Improved clearance of both apoptotic cells and bacteria in the airway may have a dual effect; reducing the risk of secondary necrosis and release of toxic cell contents that perpetuate inflammation as well as contributing to a reduction in the rate of exacerbations in COPD.

• Authors: Sandra Hodge, Paul N Reynolds
• Journal: Respirology (Carlton, Vic.) (Respirology) Vol. 17 Issue 5 Pg. 802-7 (Jul 2012) ISSN: 1440-1843 [Electronic] Australia
• PMID: 22288725 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.

Chemical References

• Anti-Bacterial Agents
• Azithromycin
• Fluorescein

Topics

• Adult
• Aged
• Anti-Bacterial Agents (pharmacology)
• Apoptosis
• Azithromycin (pharmacology)
• Bronchoalveolar Lavage
• Bronchoscopy
• Dose-Response Relationship, Drug
• Escherichia coli
• Female
• Fluorescein
• Humans
• Longitudinal Studies
• Macrophages (drug effects, pathology, physiology)
• Macrophages, Alveolar (drug effects, pathology, physiology)
• Male
• Middle Aged
• Necrosis
• Phagocytosis (drug effects, physiology)
• Pulmonary Disease, Chronic Obstructive (pathology)
• Treatment Outcome