Neutrophil-Delivered Myeloperoxidase Dampens the Hydrogen Peroxide Burst after Tissue Wounding in Zebrafish
- Pase, L; Layton, JE; Wittmann, C; Ellett, F; Nowell, CJ; Reyes-Aldasoro, CC; Varma, S; Rogers, KL; Hall, CJ; Keightley, MC; Crosier, PS; Grabher, C; Heath, JK; Renshaw, SA; Lieschke, GJ;
Publication Year 2012-10-09, Volume 22, Issue #19, Page 1818-1824
- Journal Title
- CURRENT BIOLOGY
- Publication Type
- Journal Article
- Prompt neutrophil arrival is critical for host defense immediately after injury [1-3]. Following wounding, a hydrogen peroxide (H2O2) burst generated in injured tissues is the earliest known leukocyte chemoattractant . Generating this tissue-scale H2O2 gradient uses dual oxidase  and neutrophils sense H2O2 by a mechanism involving the LYN Src-family kinase , but the molecular mechanisms responsible for H2O2 clearance are unknown . 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 H2O2 concentrations that follow wounding. This was tested in zebrafish using simultaneous fluorophore-based imaging of H2O2 concentrations and leukocytes [4,9-11] and a new neutrophil-replete but myeloperoxidase-deficient mutant (durif). Leukocyte-depleted zebrafish had an abnormally sustained wound H2O2 burst, indicating that leukocytes themselves were required for H2O2 downregulation. Myeloperoxidase-deficient zebrafish also had abnormally sustained high wound H2O2 concentrations despite similar numbers of arriving neutrophils. A local H2O2/myeloperoxidase interaction within wound-recruited neutrophils was demonstrated. These data demonstrate that leukocyte-delivered myeloperoxidase cell-autonomously downregulates tissue-generated wound H2O2 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.
- CELL PRESS
- DEFICIENCY; IMMUNITY; INNATE; INFLAMMATION; MICROBES; MODEL; MICE
- WEHI Research Division(s)
- Cancer And Haematology
- Publisher's Version
- Rights Notice
- Copyright © 2012 Elsevier Ltd. All rights reserved.
Creation Date: 2012-10-09 12:00:00Last Modified: 0001-01-01 12:00:00