ZFIN ID: ZDB-PUB-111129-4
Lyn is a redox sensor that mediates leukocyte wound attraction in vivo
Yoo, S.K., Starnes, T.W., Deng, Q., and Huttenlocher, A.
Date: 2011
Source: Nature   480(7375): 109-12 (Journal)
Registered Authors: Huttenlocher, Anna
Keywords: none
MeSH Terms:
  • Animals
  • Cells, Cultured
  • HEK293 Cells
  • Humans
  • Hydrogen Peroxide/metabolism
  • Larva
  • Neutrophils/enzymology*
  • Oxidation-Reduction*
  • Wounds and Injuries/enzymology*
  • Zebrafish/metabolism
  • Zebrafish/physiology*
  • Zebrafish Proteins/metabolism*
  • src-Family Kinases/metabolism*
PubMed: 22101434 Full text @ Nature
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ABSTRACT

Tissue wounding induces the rapid recruitment of leukocytes1. Wounds and tumours-a type of 'unhealed wound'2-generate hydrogen peroxide (H2O2) through an NADPH oxidase (NOX). This extracellular H2O2 mediates recruitment of leukocytes, particularly the first responders of innate immunity, neutrophils, to injured tissue3, 4, 5, 6. However, the sensor that neutrophils use to detect the redox state at wounds is unknown. Here we identify the Src family kinase (SFK) Lyn as a redox sensor that mediates initial neutrophil recruitment to wounds in zebrafish larvae. Lyn activation in neutrophils is dependent on wound-derived H2O2 after tissue injury, and inhibition of Lyn attenuates neutrophil wound recruitment. Inhibition of SFKs also disrupted H2O2-mediated chemotaxis of primary human neutrophils. In vitro analysis identified a single cysteine residue, C466, as being responsible for direct oxidation-mediated activation of Lyn. Furthermore, transgenic-tissue-specific reconstitution with wild-type Lyn and a cysteine mutant revealed that Lyn C466 is important for the neutrophil wound response and downstream signalling in vivo. This is the first identification, to our knowledge, of a physiological redox sensor that mediates leukocyte wound attraction in multicellular organisms.

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