|
 |
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Copyright ©ERS Journals Ltd 2006
Azithromycin increases phagocytosis of apoptotic bronchial epithelial cells by alveolar macrophages
Dept of Thoracic Medicine, Royal Adelaide Hospital and Lung Research Laboratory, Hanson Institute, Adelaide, Australia.
CORRESPONDENCE: S. Hodge, Lung Research, Hanson Institute, Frome Rd, Adelaide, 5001, South Australia. Fax: 61 881616043. E-mail: sandy.hodge{at}imvs.sa.gov.au
Keywords: Alveolar macrophage, apoptosis, azithromycin, chronic obstructive pulmonary disease, phagocytosis
Received: January 4, 2006
Accepted May 15, 2006
Chronic obstructive pulmonary disease (COPD) is associated with increased apoptosis and defective phagocytosis in the airway. As uncleared cells can undergo secondary necrosis and perpetuate inflammation, strategies to improve clearance would have therapeutic significance. There is evidence that the 15-member macrolide antibiotic azithromycin has anti-inflammatory properties. Its effects may be increased in the lung due to its ability to reach high concentrations in alveolar macrophages (AMs).
The present study investigated the effects of low-dose (500 ng·mL-1) azithromycin on the phagocytosis of apoptotic bronchial epithelial cells and neutrophils by AMs. Flow cytometry was applied to measure phagocytosis and receptors involved in AM recognition of apoptotic cells. Cytokines were investigated using cytometric bead array.
Baseline phagocytosis was reduced in COPD subjects compared with controls. Azithromycin significantly improved the phagocytosis of epithelial cells or neutrophils by AMs from COPD subjects by 68 and 38%, respectively, often up to levels comparable with controls.
The increase in phagocytosis was partially inhibited by phosphatidylserine, implicating the phosphatidylserine pathway in the pro-phagocytic effects of azithromycin. Azithromycin had no effect on other recognition molecules (granulocyte-macrophage colony-stimulating factor, CD44, CD31, CD36, CD91,
vß3 integrin). At higher doses, azithromycin decreased levels of pro-inflammatory cytokines. Thus, low-dose azithromycin therapy could provide an adjunct therapeutic option in chronic obstructive pulmonary disease.
This article has been cited by other articles:
|
|
 |
|
  S. Hodge, G. Matthews, M. M. Dean, J. Ahern, M. Djukic, G. Hodge, H. Jersmann, M. Holmes, and P. N. Reynolds Therapeutic Role for Mannose-Binding Lectin in Cigarette Smoke-Induced Lung Inflammation?: Evidence from a Murine Model Am. J. Respir. Cell Mol. Biol., February 1, 2010; 42(2): 235 - 242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. R. Richens, D. J. Linderman, S. A. Horstmann, C. Lambert, Y.-Q. Xiao, R. L. Keith, D. M. Boe, K. Morimoto, R. P. Bowler, B. J. Day, et al. Cigarette Smoke Impairs Clearance of Apoptotic Cells through Oxidant-dependent Activation of RhoA Am. J. Respir. Crit. Care Med., June 1, 2009; 179(11): 1011 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. F Idris, E. R Chilvers, C. Haworth, D. McKeon, and A. M Condliffe Azithromycin therapy for neutrophilic airways disease: myth or magic? Thorax, March 1, 2009; 64(3): 186 - 189. [Full Text] [PDF]
|
|
|
|
|
|
A. Kazeros, B.-G. Harvey, B. J. Carolan, H. Vanni, A. Krause, and R. G. Crystal Overexpression of Apoptotic Cell Removal Receptor MERTK in Alveolar Macrophages of Cigarette Smokers Am. J. Respir. Cell Mol. Biol., December 1, 2008; 39(6): 747 - 757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hodge, G. Hodge, H. Jersmann, G. Matthews, J. Ahern, M. Holmes, and P. N. Reynolds Azithromycin Improves Macrophage Phagocytic Function and Expression of Mannose Receptor in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., July 15, 2008; 178(2): 139 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Braganza, R. Chaudhuri, and N. C. Thomson Review: Treating patients with respiratory disease who smoke Therapeutic Advances in Respiratory Disease, April 1, 2008; 2(2): 95 - 107. [Abstract] [PDF]
|
|
|
|
 |
|
 B. S. Murphy, V. Sundareshan, T. J. Cory, D. Hayes Jr, M. I. Anstead, and D. J. Feola Azithromycin alters macrophage phenotype J. Antimicrob. Chemother., March 1, 2008; 61(3): 554 - 560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Simpson, H. Powell, M. J. Boyle, R. J. Scott, and P. G. Gibson Clarithromycin Targets Neutrophilic Airway Inflammation in Refractory Asthma Am. J. Respir. Crit. Care Med., January 15, 2008; 177(2): 148 - 155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. D. Starner, J. D. Shrout, M. R. Parsek, P. C. Appelbaum, and G. Kim Subinhibitory Concentrations of Azithromycin Decrease Nontypeable Haemophilus influenzae Biofilm Formation and Diminish Established Biofilms Antimicrob. Agents Chemother., January 1, 2008; 52(1): 137 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hodge, G. Hodge, J. Ahern, H. Jersmann, M. Holmes, and P. N. Reynolds Smoking Alters Alveolar Macrophage Recognition and Phagocytic Ability: Implications in Chronic Obstructive Pulmonary Disease Am. J. Respir. Cell Mol. Biol., December 1, 2007; 37(6): 748 - 755. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |