Article (Scientific journals)
The 5-phosphatase SHIP2 promotes neutrophil chemotaxis and recruitment.
Michael, Melina; McCormick, Barry; Anderson, Karen E. et al.
2021In Frontiers in Immunology
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Abstract :
[en] Neutrophils, the most abundant circulating leukocytes in humans have key roles in host defense and in the inflammatory response. Agonist-activated phosphoinositide 3-kinases (PI3Ks) are important regulators of many facets of neutrophil biology. PIP3 is subject to dephosphorylation by several 5' phosphatases, including SHIP family phosphatases, which convert the PI3K product and lipid second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3) into PI(3,4)P2, a lipid second messenger in its own right. In addition to the leukocyte restricted SHIP1, neutrophils express the ubiquitous SHIP2. This study analyzed mice and isolated neutrophils carrying a catalytically inactive SHIP2, identifying an important regulatory function in neutrophil chemotaxis and directionality in vitro and in neutrophil recruitment to sites of sterile inflammation in vivo, in the absence of major defects of any other neutrophil functions analyzed, including, phagocytosis and the formation of reactive oxygen species. Mechanistically, this is explained by a subtle effect on global 3-phosphorylated phosphoinositide species. This work identifies a non-redundant role for the hitherto overlooked SHIP2 in the regulation of neutrophils, and specifically, neutrophil chemotaxis/trafficking. It completes an emerging wider understanding of the complexity of PI3K signaling in the neutrophil, and the roles played by individual kinases and phosphatases within.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Michael, Melina
McCormick, Barry
Anderson, Karen E.
Karmakar, Utsa
Vermeren, Matthieu
Schurmans, Stéphane  ;  Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > Biochimie métabolique vétérinaire
Amour, Augustin
Vermeren, Sonja
Language :
Title :
The 5-phosphatase SHIP2 promotes neutrophil chemotaxis and recruitment.
Publication date :
Journal title :
Frontiers in Immunology
Publisher :
Frontiers Research Foundation, Lausanne, Switzerland
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 01 April 2021


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