Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Lyn is a redox sensor that mediates leukocyte wound attraction in vivo.

Nature | Dec 1, 2011

http://www.ncbi.nlm.nih.gov/pubmed/22101434

Tissue wounding induces the rapid recruitment of leukocytes. Wounds and tumours--a type of 'unhealed wound'--generate hydrogen peroxide (H(2)O(2)) through an NADPH oxidase (NOX). This extracellular H(2)O(2) mediates recruitment of leukocytes, particularly the first responders of innate immunity, neutrophils, to injured tissue. 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 H(2)O(2) after tissue injury, and inhibition of Lyn attenuates neutrophil wound recruitment. Inhibition of SFKs also disrupted H(2)O(2)-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.

Pubmed ID: 22101434 RIS Download

Mesh terms: Animals | Cells, Cultured | HEK293 Cells | Humans | Hydrogen Peroxide | Larva | Neutrophils | Oxidation-Reduction | Wounds and Injuries | Zebrafish | Zebrafish Proteins | src-Family Kinases

Research resources used in this publication

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NHLBI NIH HHS, Id: 5T32 HL07899
  • Agency: NHLBI NIH HHS, Id: F30 HL114143
  • Agency: NIGMS NIH HHS, Id: GM074827
  • Agency: NIGMS NIH HHS, Id: R01 GM074827
  • Agency: NIGMS NIH HHS, Id: R01 GM074827-08

ZFIN (Data, Gene Expression)

Addgene (Reagent, Plasmid)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.