Journal article

Neutrophil-delivered myeloperoxidase dampens the hydrogen peroxide burst after tissue wounding in zebrafish

L Pase, JE Layton, C Wittmann, F Ellett, CJ Nowell, CC Reyes-Aldasoro, S Varma, KL Rogers, CJ Hall, MC Keightley, PS Crosier, C Grabher, JK Heath, SA Renshaw, GJ Lieschke

Current Biology | Published : 2012

Abstract

Prompt neutrophil arrival is critical for host defense immediately after injury [1-3]. Following wounding, a hydrogen peroxide (H2O 2) burst generated in injured tissues is the earliest known leukocyte chemoattractant [4]. Generating this tissue-scale H2O2 gradient uses dual oxidase [4] and neutrophils sense H2O2 by a mechanism involving the LYN Src-family kinase [5], but the molecular mechanisms responsible for H2O2 clearance are unknown [6]. Neutrophils carry abundant amounts of myeloperoxidase, an enzyme catalyzing an H2O2-consuming reaction [7, 8]. We hypothesized that this neutrophil-delivered myeloperoxidase downregulates the high tissue H 2O2 concentrations that follow wounding. This ..

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University of Melbourne Researchers

Grants

Awarded by State Government of Victoria


Funding Acknowledgements

We thank J. Hayman (technical assistance); M. Greer, K. Turner, and P. Chamberlain (aquarium care); W. Alexander, N. Nicola, N. Rosenthal, and B. Croker (discussions); T. Speed and M. Olshansky (statistical advice); S. Jane, D. Curtis, and RMH-BMRL (support); and the Centre for Advanced Microscopy (Ludwig Institute for Cancer Research) and the Australian Cancer Research Foundation Centre for Therapeutic Target Discovery (microscopy). See Supplemental Information for ethics committee over-sight. Grant support is as follows: G.J.L., National Institutes of Health (R01 HL079545), National Health and Medical Resource Council (234708, 461208, 637394), and Australian Research Council (DP0346823); L.P., Australian Postgraduate Award, Walter and Eliza Hall Institute Edith Moffatt Scholarship; C.W., PhD fellowship from the Helmholtz program "Bio-Interfaces international graduate school" (BIFIGS); C.G., KIT-RISC grant, Marie Curie International Reintegration Grant within the Seventh European Community Framework Program (PIRG07-GA-2010-267552); and S.A.R., MRC Senior Clinical Fellowship (G0701932). The Australian Regenerative Medicine Institute and WEHI are supported by grants from the State Government of Victoria and the Australian Government.