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Cited by 118Neutrophil, Myeloperoxidase and Oxidative MechanismsRedox biology and oxidative stressWound Healing and Treatments

The DOI matches its Crossref record; 31 of the 32 references it cites were found in a registry or an index.

Neutrophil-Delivered Myeloperoxidase Dampens the Hydrogen Peroxide Burst after Tissue Wounding in Zebrafish

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Pase, Luke, Layton, Judith E., Wittmann, Christine, Ellett, Felix, Nowell, Cameron J., Reyes-Aldasoro, Constantino Carlos, Varma, Sony, Rogers, Kelly L., Hall, Chris J., Keightley, M. Cristina, Crosier, Philip S., Grabher, Clemens, Heath, Joan K., Renshaw, Stephen A., Lieschke, Graham J.·2012·Current Biology
DOI 10.1016/j.cub.2012.07.060
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Abstract

Prompt neutrophil arrival is critical for host defense immediately after injury [1-3]. Following wounding, a hydrogen peroxide (H(2)O(2)) burst generated in injured tissues is the earliest known leukocyte chemoattractant [4]. Generating this tissue-scale H(2)O(2) gradient uses dual oxidase [4] and neutrophils sense H(2)O(2) by a mechanism involving the LYN Src-family kinase [5], but the molecular mechanisms responsible for H(2)O(2) clearance are unknown [6]. Neutrophils carry abundant amounts of myeloperoxidase, an enzyme catalyzing an H(2)O(2)-consuming reaction [7, 8]. We hypothesized that this neutrophil-delivered myeloperoxidase downregulates the high tissue H(2)O(2) concentrations that follow wounding. This was tested in zebrafish using simultaneous fluorophore-based imaging of H(2)O(2) concentrations and leukocytes [4, 9-11] and a new neutrophil-replete but myeloperoxidase-deficient mutant (durif). Leukocyte-depleted zebrafish had an abnormally sustained wound H(2)O(2) burst, indicating that leukocytes themselves were required for H(2)O(2) downregulation. Myeloperoxidase-deficient zebrafish also had abnormally sustained high wound H(2)O(2) concentrations despite similar numbers of arriving neutrophils. A local H(2)O(2)/myeloperoxidase interaction within wound-recruited neutrophils was demonstrated. These data demonstrate that leukocyte-delivered myeloperoxidase cell-autonomously downregulates tissue-generated wound H(2)O(2) gradients in vivo, defining a new requirement for myeloperoxidase during inflammation. Durif provides a new animal model of myeloperoxidase deficiency closely phenocopying the prevalent human disorder [7, 12, 13], offering unique possibilities for investigating its clinical consequences.

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Metadata

Authors
Pase, L., Layton, J. E., Wittmann, C., Ellett, F., Nowell, C. J., Reyes-Aldasoro, C. C., Varma, S., Rogers, K. L., Hall, C. J., Keightley, M. C., Crosier, P. S., Grabher, C., Heath, J. K., Renshaw, S. A., & Lieschke, G. J.
Affiliations
  • The University of Melbourne (AU)
  • Walter and Eliza Hall Institute of Medical Research (AU)
  • Karlsruhe Institute of Technology (DE)
  • Ludwig Cancer Research (BE)
  • Australian Regenerative Medicine Institute (AU)
  • University of Auckland (NZ)
  • University of Sheffield (GB)
Corresponding author
Lieschke, Graham J.
ORCID
Venue
Current Biology
Publisher
Elsevier BV
Published
2012-10
Volume
22
Issue
19
Pages
1818-1824
ISSN
0960-9822 (ISSN-L)
DOI
10.1016/j.cub.2012.07.060
OpenAlex
W2171239786
Cited by
118
References
32
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 8 · 2022: 3 · 2021: 10 · 2020: 13 · 2019: 11 · 2018: 13 · 2017: 5 · 2016: 7 · 2015: 12 · 2014: 16 · 2013: 8 · 2012: 1
FWCI
5.15
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Biology (publishedVersion)
  • PubMed (publishedVersion)
  • City Research Online (City University London) (acceptedVersion)
  • Figshare (submittedVersion, cc-by)
  • ResearchSpace (University of Auckland) (submittedVersion)
Funders
National Heart, Lung, and Blood Institute (R01HL079545)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Surgery › Wound Healing and Treatments
Keywords
myeloperoxidase, neutrophils, hydrogen peroxide, wound healing, tissue damage, dual oxidase, Lyn kinase, myeloperoxidase deficiency, inflammation, leukocyte recruitment, zebrafish
MeSH terms
Animals, Hydrogen Peroxide, Leukocytes, Mutation, Peroxidase, Neutrophils, Zebrafish, Neutrophil Infiltration, Animals, Genetically Modified

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