Related Experiment Video
Updated: May 31, 2026
Murine Intrapulmonary Tracheal Transplantation: A Model for Investigating Obliterative Airway Disease After Lung Transplantation
Published on: November 10, 2023
Azithromycin decreases MMP-9 expression in the airways of lung transplant recipients
Stijn E Verleden1, Jennifer Vandooren, Robin Vos
1Leuven Lung Transplant Unit, KU Leuven and UZ Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
Abstract:
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 lavaga fluid in 10 stable patients and in 10 lung transplant patients suffering from nCLAD/NRAD. MMP-9 was measured via ELISA before and after 3 to 6 months 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), 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 3-6 months 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.
Insights
Azithromycin treatment reduced airway neutrophilia and matrix metalloproteinase-9 (MMP-9) activity in chronic lung allograft dysfunction/no-reflow allograft dysfunction patients. However, inflammation markers remained elevated, suggesting azithromycin may be more effective as a preventive therapy.
Area of Science:
- Pulmonology
- Immunology
- Pharmacology
Background:
- Azithromycin, a neomacrolide antibiotic, exhibits anti-inflammatory properties and is used for chronic inflammatory pulmonary diseases.
- Matrix remodeling, particularly involving matrix metalloproteinase-9 (MMP-9), plays a role in chronic lung conditions.
Purpose of the Study:
- To investigate the effect of azithromycin on matrix remodeling in patients with chronic lung allograft dysfunction/no-reflow allograft dysfunction (nCLAD/NRAD).
- To assess changes in MMP-9 levels and activity following azithromycin therapy.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) and gelatin zymography were used to measure MMP-9 protein levels and activity in bronchoalveolar lavage fluid.
- Differential and total cell counts were performed on bronchoalveolar lavage fluid.
- Measurements were taken before and after 3-6 months of azithromycin treatment in stable and lung transplant patients.
Main Results:
- nCLAD/NRAD patients exhibited higher airway neutrophilia, MMP-9 levels, and gelatinolytic activity compared to controls.
- Azithromycin therapy significantly decreased airway neutrophilia, activated MMP-9, and gelatinolytic activity.
- ProMMP-9 levels were not affected by azithromycin, while activated MMP-9 and gelatinolytic activity remained elevated compared to controls post-treatment.
Conclusions:
- Azithromycin effectively reduces airway inflammation and MMP-9 activity in nCLAD/NRAD patients.
- The treatment did not fully restore chronic airway inflammation, as some markers remained elevated.
- Preventive azithromycin therapy might offer greater benefits than curative therapy for these conditions.
Related Concept Videos
01:19Antiasthma Drugs: Leukotriene Modifiers
Leukotriene modifiers work through two distinct mechanisms:
01:25Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...