ArticleAmerican journal of physiology. Lung cellular and molecular physiology2013
Nonantibiotic macrolides prevent human neutrophil elastase-induced mucus stasis and airway surface liquid volume depletion.
Article in American journal of physiology. Lung cellular and molecular physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Trial
- Vaping-Induced Proteolysis Causes Airway Surface Dehydration.International journal of molecular sciences · 2023Article
- Article
- E-cigarette constituents propylene glycol and vegetable glycerin decrease glucose uptake and its metabolism in airway epithelial cells in vitro.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2020Article
- Role of Spdef in the Regulation of Muc5b Expression in the Airways of Naive and Mucoobstructed Mice.American journal of respiratory cell and molecular biology · 2018Article
- Lung disease phenotypes caused by overexpression of combinations of α-, β-, and γ-subunits of the epithelial sodium channel in mouse airways.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Ion channels of the lung and their role in disease pathogenesis.American journal of physiology. Lung cellular and molecular physiology · 2017Review
- Nonantibiotic macrolides restore airway macrophage phagocytic function with potential anti-inflammatory effects in chronic lung diseases.American journal of physiology. Lung cellular and molecular physiology · 2017Article
- The chronic bronchitis phenotype in chronic obstructive pulmonary disease: features and implications.Current opinion in pulmonary medicine · 2015Review
- CFTR and lung homeostasis.American journal of physiology. Lung cellular and molecular physiology · 2014Review
- Cathepsin B contributes to Na+ hyperabsorption in cystic fibrosis airway epithelial cultures.The Journal of physiology · 2014Article
- Accumulation of metals in GOLD4 COPD lungs is associated with decreased CFTR levels.Respiratory research · 2014Article
- Azithromycin analogue CSY0073 attenuates lung inflammation induced by LPS challenge.British journal of pharmacology · 2014Article
- Cigarette smoke and CFTR: implications in the pathogenesis of COPD.American journal of physiology. Lung cellular and molecular physiology · 2013Review
- Biotic acts of antibiotics.Frontiers in microbiology · 2013Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Mucus clearance is an important component of the lung's innate defense system. A failure of this system brought on by mucus dehydration is common to both cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Mucus clearance rates are regulated by the volume of airway surface liquid (ASL) and by ciliary beat frequency (CBF). Chronic treatment with macrolide antibiotics is known to be beneficial to both CF and COPD patients. However, chronic macrolide usage may induce bacterial resistance. We have developed a novel macrolide, 2'-desoxy-9-(S)-erythromycylamine (GS-459755), that has significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and Haemophilus influenzae. Since neutrophilia frequently occurs in chronic lung disease and human neutrophil elastase (HNE) induces mucus stasis by activating the epithelial sodium channel (ENaC), we tested the ability of GS-459755 to protect against HNE-induced mucus stasis. GS-459755 had no effect on HNE activity. However, GS-459755 pretreatment protected against HNE-induced ASL volume depletion in human bronchial epithelial cells (HBECs). The effect of GS-459755 on ASL volume was dose dependent (IC₅₀ ~3.9 μM) and comparable to the antibacterial macrolide azithromycin (IC₅₀ ~2.4 μM). Macrolides had no significant effect on CBF or on transepithelial water permeability. However, the amiloride-sensitive transepithelial voltage, a marker of ENaC activity, was diminished by macrolide pretreatment. We conclude that GS-459755 may limit HNE-induced activation of ENaC and may be useful for the treatment of mucus dehydration in CF and COPD without inducing bacterial resistance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.