Evidence map›Paper›PMID 10811853›Full record

ArticleThe Journal of clinical investigation2000

Eosinophils generate brominating oxidants in allergen-induced asthma.

W Wu, M K Samoszuk, S A Comhair, M J Thomassen, C F Farver, R A Dweik, M S Kavuru, S C Erzurum, S L Hazen

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01536522 (Asthma Inflammation Research), which is not on this map. Cited by 100 papers.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed
10.5field-weighted citation impact, top 1% 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.

NCT01536522 early_phase1enrolling by invitationnot on this mapstarted 2011, after this paper: background citation

Asthma Inflammation Research

TypeinterventionalSponsorThe Cleveland ClinicRan2011 to 2027Enrolled60ConditionsAsthma, Allergic Asthma, Non-allergic AsthmaArmsNutritional approach for asthma, Low Caloric Shake, whole lung allergen challenge
3 · Its place in the literature

Who cites it

100 citing papers in PubMed, 283 citations in OpenAlex.

  1. Article
  2. Frequent exacerbator-a novel endotype of pediatric asthma.The Journal of allergy and clinical immunology · 2025
    Review
  3. Article
  4. Eosinophil extracellular traps in respiratory ailment: Pathogenic mechanisms and clinical translation.World journal of otorhinolaryngology - head and neck surgery · 2024
    Review
  5. Diacron-Reactive Oxygen Metabolites Levels Are Initially Elevated in Patients with Bullous Pemphigoid.JID innovations : skin science from molecules to population health · 2024
    Article
  6. Review
  7. Misregulation of bromotyrosine compromises fertility in maleProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Urinary total conjugated 3-bromotyrosine, asthma severity, and exacerbation risk.American journal of physiology. Lung cellular and molecular physiology · 2022
    Article
  14. Halogenation Activity of Mammalian Heme Peroxidases.Antioxidants (Basel, Switzerland) · 2022
    Review
  15. Article
  16. Article
  17. Heme Peroxidases at Unperturbed and Inflamed Mucous Surfaces.Antioxidants (Basel, Switzerland) · 2021
    Review
  18. Review
  19. Review
  20. Review

40 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

W WuDepartment of Cell Biology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
M K Samoszuk
S A Comhair
M J Thomassen
C F Farver
R A Dweik
M S Kavuru
S C Erzurum
S L Hazen
Cleveland Clinic · USPulmonary and Critical Care Associates · USInstitute of Molecular Medicine · INQuest Diagnostics (United States) · US

Funding

Peroxidases and AsthmaR01HL061878 · NHLBI · CLEVELAND CLINIC LERNER COL/MED-CWRU · PI HAZEN, STANLEY L · 1998 to 2005
$1.7M
MYELOPEROXIDASE, OXIDANT STRESS AND ATHEROGENESISR01HL062526 · NHLBI · CLEVELAND CLINIC LERNER COL/MED-CWRU · PI HAZEN, STANLEY L · 1999 to 2004
$1.4M
NHLBI NIH HHS HL-62526NHLBI NIH HHS R01 HL061878
6 · The paper itself

Abstract

Eosinophils promote tissue injury and contribute to the pathogenesis of allergen-triggered diseases like asthma, but the chemical basis of damage to eosinophil targets is unknown. We now demonstrate that eosinophil activation in vivo results in oxidative damage of proteins through bromination of tyrosine residues, a heretofore unrecognized pathway for covalent modification of biologic targets in human tissues. Mass spectrometric studies demonstrated that 3-bromotyrosine serves as a specific "molecular fingerprint" for proteins modified through the eosinophil peroxidase-H(2)O(2) system in the presence of plasma levels of halides. We applied a localized allergen challenge to model the effects of eosinophils and brominating oxidants in human lung injury. Endobronchial biopsy specimens from allergen-challenged lung segments of asthmatic, but not healthy control, subjects demonstrated significant enrichments in eosinophils and eosinophil peroxidase. Baseline levels of 3-bromotyrosine in bronchoalveolar lavage (BAL) proteins from mildly allergic asthmatic individuals were modestly but not statistically significantly elevated over those in control subjects. After exposure to segmental allergen challenge, lung segments of asthmatics, but not healthy control subjects, exhibited a >10-fold increase in BAL 3-bromotyrosine content, but only two- to threefold increases in 3-chlorotyrosine, a specific oxidation product formed by neutrophil- and monocyte-derived myeloperoxidase. These results identify reactive brominating species produced by eosinophils as a distinct class of oxidants formed in vivo. They also reveal eosinophil peroxidase as a potential therapeutic target for allergen-triggered inflammatory tissue injury in humans.

Indexed as

AllergensAsthmaBromineBronchoalveolar Lavage FluidCase-Control StudiesEosinophilsHumansIn Vitro TechniquesLungNeutrophilsReactive Oxygen SpeciesTyrosineAllergensBromineReactive Oxygen SpeciesTyrosine

Identifiers

PMID10811853
PMCPMC315470
OpenAlexW2115561143

What OpenQuestion holds

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Registered trials

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.