Journal article

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

Luke Pase, Judith E Layton, Christine Wittmann, Felix Ellett, Cameron J Nowell, Constantino Carlos Reyes-Aldasoro, Sony Varma, Kelly L Rogers, Chris J Hall, M Cristina Keightley, Philip S Crosier, Clemens Grabher, Joan K Heath, Stephen A Renshaw, Graham J Lieschke



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 ..

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Awarded by National Institutes of Health

Awarded by National Health and Medical Resource Council

Awarded by Australian Research Council

Awarded by Marie Curie International Reintegration Grant within the Seventh European Community Framework Program

Awarded by MRC


Awarded by Medical Research Council

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.