ArticleRespiratory research2012
Leaky lysosomes in lung transplant macrophages: azithromycin prevents oxidative damage.
Article in Respiratory research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 27 citations in OpenAlex.
- A review on oxidant and antioxidant effects of antibacterial agents: impacts on bacterial cell death and division and therapeutic effects or adverse reactions in humans.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Azithromycin ameliorated cigarette smoke-induced airway epithelial barrier dysfunction by activating Nrf2/GCL/GSH signaling pathway.Respiratory research · 2023Article
- The Azithromycin Pro-Drug CSY5669 Boosts Bacterial Killing While Attenuating Lung Inflammation Associated with Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2022Article
- Azithromycin through the Lens of the COVID-19 Treatment.Antibiotics (Basel, Switzerland) · 2022Review
- Pulmonary Macrophage Cell Death in Lung Health and Disease.American journal of respiratory cell and molecular biology · 2021Review
- Azithromycin in viral infections.Reviews in medical virology · 2021Review
- Could Azithromycin Be Part ofFrontiers in microbiology · 2021Review
- Widely available lysosome targeting agents should be considered as potential therapy for COVID-19.International journal of antimicrobial agents · 2020Article
- Human Lung Macrophages Challenged to Oxidants ex vivo: Lysosomal Membrane Sensitization is Associated with Inflammation and Chronic Airflow Limitation.Journal of inflammation research · 2020Article
- Immunosuppression and allograft rejection following lung transplantation: evidence to date.Drugs · 2013Review
- Increased Lysosomal Membrane Permeabilization in Oxidant-exposed Macrophages of Human Fibrotic Lungs.Journal of cell death · 2013Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLung allografts contain large amounts of iron (Fe), which inside lung macrophages may promote oxidative lysosomal membrane permeabilization (LMP), cell death and inflammation. The macrolide antibiotic azithromycin (AZM) accumulates 1000-fold inside the acidic lysosomes and may interfere with the lysosomal pool of Fe.
objectiveOxidative lysosomal leakage was assessed in lung macrophages from lung transplant recipients without or with AZM treatment and from healthy subjects. The efficiency of AZM to protect lysosomes and cells against oxidants was further assessed employing murine J774 macrophages.
methodsMacrophages harvested from 8 transplant recipients (5 without and 3 with ongoing AZM treatment) and 7 healthy subjects, and J774 cells pre-treated with AZM, a high-molecular-weight derivative of the Fe chelator desferrioxamine or ammonium chloride were oxidatively stressed. LMP, cell death, Fe, reduced glutathione (GSH) and H-ferritin were assessed.
resultsOxidant challenged macrophages from transplants recipients without AZM exhibited significantly more LMP and cell death than macrophages from healthy subjects. Those macrophages contained significantly more Fe, while GSH and H-ferritin did not differ significantly. Although macrophages from transplant recipients treated with AZM contained both significantly more Fe and less GSH, which would sensitize cells to oxidants, these macrophages resisted oxidant challenge well. The preventive effect of AZM on oxidative LMP and J774 cell death was 60 to 300 times greater than the other drugs tested.
conclusionsAZM makes lung transplant macrophages and their lysososomes more resistant to oxidant challenge. Possibly, prevention of obliterative bronchiolitis in lung transplants by AZM is partly due to this action.
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