Evidence map›Paper›PMID 23542952›Full record

ArticleAmerican journal of physiology. Lung cellular and molecular physiology2013

Nonantibiotic macrolides prevent human neutrophil elastase-induced mucus stasis and airway surface liquid volume depletion.

Robert Tarran, Juan R Sabater, Tainya C Clarke, Chong D Tan, Catrin M Davies, Jia Liu, Arthur Yeung, Alaina L Garland, M Jackson Stutts, William M Abraham and 4 more

Open access · greenAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 36 citations in OpenAlex.

  1. Trial
  2. Vaping-Induced Proteolysis Causes Airway Surface Dehydration.International journal of molecular sciences · 2023
    Article
  3. Article
  4. Article
  5. 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.] · 2020
    Article
  6. Article
  7. Article
  8. Ion channels of the lung and their role in disease pathogenesis.American journal of physiology. Lung cellular and molecular physiology · 2017
    Review
  9. Article
  10. Review
  11. CFTR and lung homeostasis.American journal of physiology. Lung cellular and molecular physiology · 2014
    Review
  12. Article
  13. Article
  14. Article
  15. Cigarette smoke and CFTR: implications in the pathogenesis of COPD.American journal of physiology. Lung cellular and molecular physiology · 2013
    Review
  16. Biotic acts of antibiotics.Frontiers in microbiology · 2013
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Robert TarranCystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, NC 27516, USA. robert_tarran@med.unc.edu
Juan R Sabater
Tainya C Clarke
Chong D Tan
Catrin M Davies
Jia Liu
Arthur Yeung
Alaina L Garland
M Jackson Stutts
William M Abraham
Gary Phillips
William R Baker
Clifford D Wright
Sibylle Wilbert
Gilead Sciences (United States) · USUniversity of North Carolina at Chapel Hill · USMount Sinai Medical Center · US

Funding

SPLUNC1-Derived Peptides as ENaC AntagonistsR01HL108927 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TARRAN, ROBERT · 2012 to 2015
$1.4M
NHLBI NIH HHS R01 HL108927
6 · The paper itself

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.

Indexed as

AzithromycinEpithelial Sodium ChannelsErythromycinHumansLeukocyte ElastaseMacrolidesMucusRespiratory MucosaRespiratory System2'-desoxy-9-erythromycylamineAzithromycinEpithelial Sodium ChannelsErythromycinLeukocyte ElastaseMacrolidesCOPDENaCepitheliaproteasesodium absorption

Identifiers

PMID23542952
PMCPMC3680760
OpenAlexW2122466842

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.