Lyn is a redox sensor that mediates leukocyte wound attraction in vivo (Nature, 2011, 480:109-112)

報告日期: 2012/06/19
報告時間: 14:10/15:00
報告學生: 蕭尊先
講評老師: 傅子芳
附件下載: 下載[1203-1334225320-1.pdf] 

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

Sa Kan Yoo, Taylor W. Starnes, Qing Deng2 and Anna Huttenlocher

Nature. 480:109-12. 2011

 

Student: Tsun-Hsien Hsiao                                  Place: Room 601

Commentator: Dr. Tzu-Fun Fu                   Time: 2012/6/12 15:00 ~16:00

 

Abstract

Leukocytes, including neutrophils and macrophages, are rapidly recruited when tissue are wounded. The prevailing view is that leukocytes are attracted to wound sites via signals, such as ATP, lipids and nuclear proteins, and release hydrogen peroxide (H2O2) to limit the infection. Recently, one study reported that tissue injuring generates a rapid concentration gradient of H2O2 which provided the critical first chemoattractant for leukocytes recruitment to the wound site. These data suggested that H2O2 production in the injured site by epithelial Duox, an NADPH oxidase, mediates the initial killing of bacteria and recruitment of leukocytes, especially neutrophils, to amplify the immune response. However, how neutrophils sense the redox and migrate toward the wounds is still unknown. In this study, the authors used zebrafish as an animal model and identified the Src family kinases (SFKs) as a redox sensor for neutrophils attraction. Knockdown of Duox results in inhibition of SFKs phosphorylation. Inhibition of SFKs leads to attenuation of neitrophils attraction to the wounds site. Among 9 members of Src family kinases, only Lyn is expressed in neutrophil. Knockdown of Lyn also attenuates the neutrophils attraction to the injured site and phosphorylation of SFKs in the neutrophil. The data suggested that Lyn is primarily responsible for SFK in the wounds. Furthermore, the authors found that the oxidation of Lyn C466 residue is important for redox sensing rather than basal activity. The authors also characterized the underlying mechanism, showing that Lyn senses H2O2 and mediates the subsequent recruitment of neutrophils through Erk signaling. In conclusion, Lyn oxidized on C466 residue by H2O2 when tissue wounding, is the redox sensor that mediates the recruitment of neutrophils through Erk activation.

 

References

  1. Yoo SK and Huttenlocher A. Innate immunity: wounds burst H2O2 signals to leukocytes. Curr Biol. 19:R553-5. 2009.
  2. Niethammer, P., Grabher, C., Look, A. T. & Mitchison, T. J. A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature. 459: 996–999. 2009.