Cargando…

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

Tissue wounding induces the rapid recruitment of leukocytes(1). Wounds and tumors, a type of “unhealed wound”(2), generate hydrogen peroxide (H(2)O(2)) through a NADPH oxidase (NOX) and the extracellular H(2)O(2) mediates recruitment of leukocytes, particularly first responders of innate immunity, n...

Descripción completa

Detalles Bibliográficos
Autores principales: Yoo, Sa Kan, Starnes, Taylor W., Deng, Qing, Huttenlocher, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228893/
https://www.ncbi.nlm.nih.gov/pubmed/22101434
http://dx.doi.org/10.1038/nature10632
_version_ 1782217885441064960
author Yoo, Sa Kan
Starnes, Taylor W.
Deng, Qing
Huttenlocher, Anna
author_facet Yoo, Sa Kan
Starnes, Taylor W.
Deng, Qing
Huttenlocher, Anna
author_sort Yoo, Sa Kan
collection PubMed
description Tissue wounding induces the rapid recruitment of leukocytes(1). Wounds and tumors, a type of “unhealed wound”(2), generate hydrogen peroxide (H(2)O(2)) through a NADPH oxidase (NOX) and the extracellular H(2)O(2) mediates recruitment of leukocytes, particularly first responders of innate immunity, neutrophils, to injured tissue(3–6). However, it is not known what sensor neutrophils use to detect the redox state at wounds. 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) following 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 signaling in vivo. This is the first identification, to our knowledge, of a physiological redox sensor that mediates leukocyte wound attraction in multicellular organisms.
format Online
Article
Text
id pubmed-3228893
institution National Center for Biotechnology Information
language English
publishDate 2011
record_format MEDLINE/PubMed
spelling pubmed-32288932012-06-01 Lyn is a redox sensor that mediates leukocyte wound attraction in vivo Yoo, Sa Kan Starnes, Taylor W. Deng, Qing Huttenlocher, Anna Nature Article Tissue wounding induces the rapid recruitment of leukocytes(1). Wounds and tumors, a type of “unhealed wound”(2), generate hydrogen peroxide (H(2)O(2)) through a NADPH oxidase (NOX) and the extracellular H(2)O(2) mediates recruitment of leukocytes, particularly first responders of innate immunity, neutrophils, to injured tissue(3–6). However, it is not known what sensor neutrophils use to detect the redox state at wounds. 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) following 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 signaling in vivo. This is the first identification, to our knowledge, of a physiological redox sensor that mediates leukocyte wound attraction in multicellular organisms. 2011-11-20 /pmc/articles/PMC3228893/ /pubmed/22101434 http://dx.doi.org/10.1038/nature10632 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Yoo, Sa Kan
Starnes, Taylor W.
Deng, Qing
Huttenlocher, Anna
Lyn is a redox sensor that mediates leukocyte wound attraction in vivo
title Lyn is a redox sensor that mediates leukocyte wound attraction in vivo
title_full Lyn is a redox sensor that mediates leukocyte wound attraction in vivo
title_fullStr Lyn is a redox sensor that mediates leukocyte wound attraction in vivo
title_full_unstemmed Lyn is a redox sensor that mediates leukocyte wound attraction in vivo
title_short Lyn is a redox sensor that mediates leukocyte wound attraction in vivo
title_sort lyn is a redox sensor that mediates leukocyte wound attraction in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228893/
https://www.ncbi.nlm.nih.gov/pubmed/22101434
http://dx.doi.org/10.1038/nature10632
work_keys_str_mv AT yoosakan lynisaredoxsensorthatmediatesleukocytewoundattractioninvivo
AT starnestaylorw lynisaredoxsensorthatmediatesleukocytewoundattractioninvivo
AT dengqing lynisaredoxsensorthatmediatesleukocytewoundattractioninvivo
AT huttenlocheranna lynisaredoxsensorthatmediatesleukocytewoundattractioninvivo