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

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