Evidence map›Paper›PMID 23045615›Full record

Trial reportJournal of immunology (Baltimore, Md. : 1950)2012

Hepoxilin A(3) facilitates neutrophilic breach of lipoxygenase-expressing airway epithelial barriers.

David L Tamang, Waheed Pirzai, Gregory P Priebe, David C Traficante, Gerald B Pier, John R Falck, Christophe Morisseau, Bruce D Hammock, Beth A McCormick, Karsten Gronert and 1 more

Open access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

31 citing papers in PubMed, 37 citations in OpenAlex.

  1. Blocking HXAmBio · 2024
    Article
  2. Article
  3. Blocking HXAbioRxiv : the preprint server for biology · 2024
    Article
  4. Lipoxygenases at the Intersection of Infection and Carcinogenesis.International journal of molecular sciences · 2024
    Review
  5. Review
  6. Article
  7. Review
  8. Challenging the evidence for hepoxilin AAmerican journal of physiology. Lung cellular and molecular physiology · 2020
    Article
  9. Article
  10. Article
  11. Pneumolysin Induces 12-Lipoxygenase-Dependent Neutrophil Migration duringJournal of immunology (Baltimore, Md. : 1950) · 2020
    Article
  12. Article
  13. Review
  14. Frontiers in microbiology · 2019
    Article
  15. Article
  16. Article
  17. Article
  18. Cytosolic Phospholipase AInfection and immunity · 2017
    Article
  19. Article
  20. 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

11 authors at 8 institutions in 1 country.

David L TamangMucosal Immunology Laboratory, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Waheed Pirzai
Gregory P Priebe
David C Traficante
Gerald B Pier
John R Falck
Christophe Morisseau
Bruce D Hammock
Beth A McCormick
Karsten Gronert
Bryan P Hurley
Harvard University Press · USMassachusetts General Hospital · USUniversity of California, Davis · USBrigham and Women's Hospital · USHarvard University · USThe University of Texas Southwestern Medical Center · USUniversity of California, Berkeley · USUniversity of Massachusetts Chan Medical School · US

Funding

Xenograft and Isograft CoreP01DK033506 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI WALKER, W ALLAN · 1986 to 2015
$24.2M
INTESTINAL INFLAMMATION ORCHESTRATED BY PATHOGENSR01DK056754 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MCCORMICK, BETH A · 2000 to 2017
$6.5M
The Role of Hepoxilin A3 in Neutrophil Breach of the Infected Airway MucosaR01AI095338 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI HURLEY, BRYAN P · 2012 to 2022
$5.2M
Novel Eicosanoids: Synthesis and FunctionR01GM031278 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI FALCK, JOHN R. · 1985 to 2012
$4.7M
HYDROLYTIC ENZYMES IN THE METABOLISM OF TOXINSR01ES002710 · NIEHS · UNIVERSITY OF CALIFORNIA DAVIS · PI HAMMOCK, BRUCE D · 1985 to 2018
$4.0M
Mechanism of Cif Virulence: A Bacterial Strategy to Subvert Host-Cell DefensesR01AI091699 · NIAID · DARTMOUTH COLLEGE · PI MADDEN, DEAN R, O'TOOLE, GEORGE A. · 2012 to 2016
$2.3M
Protective Lipid Circuits in Corneal Injury and DiseaseR01EY016136 · NEI · UNIVERSITY OF CALIFORNIA BERKELEY · PI GRONERT, KARSTEN · 2005 to 2009
$1.9M
Sex-specific Regulation of Acute Inflammation and ResolutionR01EY022208 · NEI · UNIVERSITY OF CALIFORNIA BERKELEY · PI GRONERT, KARSTEN · 2012 to 2015
$1.5M
Eicosanoid Production By Infected Lung Epithelial CellsK22AI065425 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI HURLEY, BRYAN P · 2008 to 2009
$269k
NEI NIH HHS EY016136NEI NIH HHS R01 EY016136NEI NIH HHS R01 EY022208NIAID NIH HHS 1 R01 AI095338-01A1NIAID NIH HHS 5K22AI065425-02NIAID NIH HHS K22 AI065425NIAID NIH HHS R01 AI091699NIAID NIH HHS R01 AI095338NIDDK NIH HHS DK 33506NIDDK NIH HHS DK 56754NIDDK NIH HHS P01 DK033506NIDDK NIH HHS R01 DK056754NIEHS NIH HHS R01 ES002710NIGMS NIH HHS R01 GM031278NIGMS NIH HHS R01 GM31278
6 · The paper itself

Abstract

A feature shared by many inflammatory lung diseases is excessive neutrophilic infiltration. Neutrophil homing to airspaces involve multiple factors produced by several distinct cell types. Hepoxilin A(3) is a neutrophil chemoattractant produced by pathogen-infected epithelial cells that is hypothesized to facilitate neutrophil breach of mucosal barriers. Using a Transwell model of lung epithelial barriers infected with Pseudomonas aeruginosa, we explored the role of hepoxilin A(3) in neutrophil transepithelial migration. Pharmacological inhibitors of the enzymatic pathways necessary to generate hepoxilin A(3), including phospholipase A(2) and 12-lipoxygenase, potently interfere with P. aeruginosa-induced neutrophil transepithelial migration. Both transformed and primary human lung epithelial cells infected with P. aeruginosa generate hepoxilin A(3) precursor arachidonic acid. All four known lipoxygenase enzymes capable of synthesizing hepoxilin A(3) are expressed in lung epithelial cell lines, primary small airway epithelial cells, and human bronchial epithelial cells. Lung epithelial cells produce increased hepoxilin A(3) and lipid-derived neutrophil chemotactic activity in response to P. aeruginosa infection. Lipid-derived chemotactic activity is soluble epoxide hydrolase sensitive, consistent with hepoxilin A(3) serving a chemotactic role. Stable inhibitory structural analogs of hepoxilin A(3) are capable of impeding P. aeruginosa-induced neutrophil transepithelial migration. Finally, intranasal infection of mice with P. aeruginosa promotes enhanced cellular infiltrate into the airspace, as well as increased concentration of the 12-lipoxygenase metabolites hepoxilin A(3) and 12-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid. Data generated from multiple models in this study provide further evidence that hepoxilin A(3) is produced in response to lung pathogenic bacteria and functions to drive neutrophils across epithelial barriers.

Indexed as

8,11,14-Eicosatrienoic AcidAnimalsArachidonate 12-LipoxygenaseBlood-Air BarrierEpithelial CellsFemaleHumansMaleMiceNeutrophilsPneumonia, BacterialPseudomonas aeruginosaPseudomonas InfectionsRespiratory MucosaTransendothelial and Transepithelial Migration8,11,14-Eicosatrienoic Acid8-hydroxy-11,12-epoxyeicosa-5,9,14-trienoic acidArachidonate 12-Lipoxygenase

Identifiers

PMID23045615
PMCPMC3490410
OpenAlexW2114428956

What OpenQuestion holds

Textmetadata
LicenceTDM
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.