PUBLICATION

Lipid peroxidation regulates long-range wound detection through 5-lipoxygenase in zebrafish

Authors
Katikaneni, A., Jelcic, M., Gerlach, G.F., Ma, Y., Overholtzer, M., Niethammer, P.
ID
ZDB-PUB-200902-6
Date
2020
Source
Nature cell biology   22(9): 1049-1055 (Journal)
Registered Authors
Niethammer, Philipp
Keywords
none
MeSH Terms
  • Animals
  • Arachidonate 5-Lipoxygenase/metabolism*
  • Arachidonic Acid/metabolism
  • Leukocytes/metabolism
  • Lipid Peroxidation/physiology*
  • Oxidation-Reduction
  • Reactive Oxygen Species/metabolism
  • Wounds and Injuries/metabolism*
  • Zebrafish/metabolism*
PubMed
32868902 Full text @ Nat. Cell Biol.
Abstract
Rapid wound detection by distant leukocytes is essential for antimicrobial defence and post-infection survival1. The reactive oxygen species hydrogen peroxide and the polyunsaturated fatty acid arachidonic acid are among the earliest known mediators of this process2-4. It is unknown whether or how these highly conserved cues collaborate to achieve wound detection over distances of several hundreds of micrometres within a few minutes. To investigate this, we locally applied arachidonic acid and skin-permeable peroxide by micropipette perfusion to unwounded zebrafish tail fins. As in wounds, arachidonic acid rapidly attracted leukocytes through dual oxidase (Duox) and 5-lipoxygenase (Alox5a). Peroxide promoted chemotaxis to arachidonic acid without being chemotactic on its own. Intravital biosensor imaging showed that wound peroxide and arachidonic acid converged on half-millimetre-long lipid peroxidation gradients that promoted leukocyte attraction. Our data suggest that lipid peroxidation functions as a spatial redox relay that enables long-range detection of early wound cues by immune cells, outlining a beneficial role for this otherwise toxic process.
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