help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on April 17, 2008, doi:10.1164/rccm.200711-1666OC

Am. J. Respir. Crit. Care Med., Volume 178, Number 2, July 2008, 139-148

A more recent version of this article appeared on July 15, 2008
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
200711-1666OCv1
178/2/139    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hodge, S.
Right arrow Articles by Reynolds, P. N
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hodge, S.
Right arrow Articles by Reynolds, P. N

Submitted on November 11, 2007
Accepted on April 17, 2008

Azithromycin Improves Macrophage Phagocytic Function and Expression of Mannose Receptor in COPD

Sandra Hodge1*, Greg Hodge1, Hubertus Jersmann1, Geoffrey Matthews1, Jessica Ahern1, Mark Holmes1, and Paul N Reynolds1

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

* To whom correspondence should be addressed. 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 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 D (SP-D)) and mannose receptor (MR) in COPD and their possible role in the azithromycin-mediated improvement in phagocytosis. Methods: 1) In vitro effects of azithromycin on AM expression of MR were investigated. 2) MBL, SP-D and MR were measured in COPD subjects and controls. 3) Azithromycin (250mg orally daily for five days then 2x weekly (total 12 weeks)) was administered to 11 COPD subjects. Assessments included AM phagocytic ability and expression of MR, MBL, SP-D, bronchial epithelial cell apoptosis, pulmonary function, CRP, blood/BAL leucocyte counts, cytokine production and T-cell markers of activation and phenotype. Results: Azithomycin (500ng/ml) increased MR expression by 50% in vitro. AM MR expression and levels of MBL and SP-D were significantly reduced in COPD subjects vs controls. In COPD patients following azithromycin therapy, we observed significantly improved AM phagocytic ability (pre: 9.9% vs post: 15.1%), reduced bronchial epithelial cell apoptosis (pre: 30.0% vs post: 19.7%) increased MR and reduced inflammatory markers in the peripheral blood. These findings implicate the MR in both the defective phagocytic function of AM 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.
Key words: COPD, alveolar macrophage, phagocytosis, azithromycin, apoptosis




This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
M. Bosnar, B. Bosnjak, S. Cuzic, B. Hrvacic, N. Marjanovic, I. Glojnaric, O. Culic, M. J. Parnham, and V. E. Haber
Azithromycin and Clarithromycin Inhibit Lipopolysaccharide-Induced Murine Pulmonary Neutrophilia Mainly through Effects on Macrophage-Derived Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-1{beta}
J. Pharmacol. Exp. Ther., October 1, 2009; 331(1): 104 - 113.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
V. M. Borges, R. W. Vandivier, K. A. McPhillips, J. A. Kench, K. Morimoto, S. D. Groshong, T. R. Richens, B. B. Graham, A. M. Muldrow, L. V. Heule, et al.
TNF{alpha} inhibits apoptotic cell clearance in the lung, exacerbating acute inflammation
Am J Physiol Lung Cell Mol Physiol, October 1, 2009; 297(4): L586 - L595.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
A. K. A. Wright, S. Rao, S. Range, C. Eder, T. P. J. Hofer, M. Frankenberger, L. Kobzik, C. Brightling, J. Grigg, and L. Ziegler-Heitbrock
Pivotal Advance: Expansion of small sputum macrophages in CF: failure to express MARCO and mannose receptors
J. Leukoc. Biol., September 1, 2009; 86(3): 479 - 489.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
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]

Home page
 Am. J. Respir. Crit. Care Med.Home page
J. D Maclay, R. A Rabinovich, and W. MacNee
Update in Chronic Obstructive Pulmonary Disease 2008
Am. J. Respir. Crit. Care Med., April 1, 2009; 179(7): 533 - 541.
[Full Text] [PDF]

Home page
 ThoraxHome page
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]

Home page
 Am. J. Respir. Crit. Care Med.Home page
T. A. R. Seemungal, T. M. A. Wilkinson, J. R. Hurst, W. R. Perera, R. J. Sapsford, and J. A. Wedzicha
Long-term Erythromycin Therapy Is Associated with Decreased Chronic Obstructive Pulmonary Disease Exacerbations
Am. J. Respir. Crit. Care Med., December 1, 2008; 178(11): 1139 - 1147.
[Abstract] [Full Text] [PDF]

Home page
 JWatch Infect. DiseasesHome page
Azithromycin as a Treatment for COPD
Journal Watch Infectious Diseases, July 23, 2008; 2008(723): 8 - 8.
[Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2008 American Thoracic Society 		  SOTA, FL