Image-Based Measurement of H2 O2 Reaction-Diffusion in Wounded Zebrafish Larvae

Biophysical Journal
Mark JelcicPhilipp Niethammer

Abstract

Epithelial injury induces rapid recruitment of antimicrobial leukocytes to the wound site. In zebrafish larvae, activation of the epithelial NADPH oxidase Duox at the wound margin is required early during this response. Before injury, leukocytes are near the vascular region, that is, ∼100-300 μm away from the injury site. How Duox establishes long-range signaling to leukocytes is unclear. We conceived that extracellular hydrogen peroxide (H2O2) generated by Duox diffuses through the tissue to directly regulate chemotactic signaling in these cells. But before it can oxidize cellular proteins, H2O2 must get past the antioxidant barriers that protect the cellular proteome. To test whether, or on which length scales this occurs during physiological wound signaling, we developed a computational method based on reaction-diffusion principles that infers H2O2 degradation rates from intravital H2O2-biosensor imaging data. Our results indicate that at high tissue H2O2 levels the peroxiredoxin-thioredoxin antioxidant chain becomes overwhelmed, and H2O2 degradation stalls or ceases. Although the wound H2O2 gradient reaches deep into the tissue, it likely overcomes antioxidant barriers only within ∼30 μm of the wound margin. Thus, Duox-medi...Continue Reading

Citations

Jul 31, 2019·Journal of Biochemistry·Haya AlshaabiBrian Cunniff
Sep 2, 2020·Nature Cell Biology·Anushka KatikaneniPhilipp Niethammer
Dec 21, 2020·Redox Biology·Haya AlshaabiBrian Cunniff
Nov 5, 2020·International Journal of Molecular Sciences·Alexander I KostyukDmitry S Bilan
Jan 29, 2021·Antioxidants·Steen Vang PetersenFrederik Vilhardt
Jul 29, 2017·Seminars in Cell & Developmental Biology·Philipp Niethammer
May 1, 2021·Scientific Reports·Hassan MoradPeter A McNaughton

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