Document Detail

Azithromycin decreases MMP-9 expression in the airways of lung transplant recipients.
MedLine Citation:
PMID:  21740970     Owner:  NLM     Status:  Publisher    
The neomacrolide antibiotic azithromycin is known to have an anti-inflammatory effect and is increasingly being used in the treatment of chronic inflammatory pulmonary diseases. We investigated whether azithromycin influenced matrix remodeling. Matrix metalloproteinase (MMP)-9 protein levels were measured by ELISA in bronchoalveolar lavage fluid (BAL) of 10 lung transplant patients suffering from nCLAD/NRAD and 10 stable control patients. MMP-9 was measured via ELISA before and after 3 to 6months of azithromycin therapy. We further elaborated on the role of MMP-9 by performing gelatin-zymography and gelatinolytic activity assays. Differential and total cell counts on BAL were performed in all cases. The nCLAD/NRAD patients showed higher airway neutrophilia (p<0.0001), ELISA MMP-9 (p<0.0001), zymography proMMP-9 (p<0.0001) and activated MMP-9 (p=0.0003) and gelatinolytic activity (p=0.0002) compared to the control group. Airway neutrophilia in the nCLAD/NRAD group significantly decreased after 3-6months of treatment with azithromycin (p=0.0020). This was associated with a decrease in ELISA MMP-9 levels (p=0.0059), in activated MMP-9 shown on zymography (p=0.016) and in gelatinolytic activity (p=0.031). Remarkably, proMMP-9 levels were not altered by azithromycin. Although azithromycin significantly reduced ELISA MMP-9 levels and gelatinolytic activity in transplant patients, these levels remained higher compared to control patients (p=0.0011 and p=0.043). Neutrophil counts, activated MMP-9 and gelatinolytic activity levels in nCLAD/NRAD decreased after azithromycin treatment, but some remained elevated compared to control patients. This illustrates that treatment with azithromycin did not completely restore chronic inflammation in the airways and suggested that preventive therapy may yield added value to curative therapy.
Stijn E Verleden; Jennifer Vandooren; Robin Vos; Stijn Willems; Lieven J Dupont; Geert M Verleden; Dirk E Van Raemdonck; Ghislain Opdenakker; Bart M Vanaudenaerde
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-29
Journal Detail:
Title:  Transplant immunology     Volume:  -     ISSN:  1878-5492     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-7-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9309923     Medline TA:  Transpl Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
Leuven Lung transplant unit, KULeuven and UZ Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
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