Article (Scientific journals)
Regulation of innate immunity by inositol 1,3,4,5-tetrakisphosphate
Jia, Y.; Schurmans, Stéphane; Luo, H. R.
2008In Cell Cycle, 7, p. 2803-2808
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Keywords :
InsP3KB; neutrophils; Ins(1,3,4,5)P4; innate immunity; hematopoiesis; PtdIns(3,4,5)P3
Abstract :
[en] Many neutrophil functions are mediated by PtdIns(3,4,5)P3 that exerts its role by mediating protein translocation via binding to their PH-domains. Inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5) P4) binds the same PH domain, competes for its binding to PtdIns(3,4,5)P3, and thus negatively regulates PtdIns(3,4,5)P3 signaling. In neutrophils, chemoattractant stimulation triggers rapid elevation in Ins(1,3,4,5)P4 level. Depletion of Ins(1,3,4,5) P4 by deleting InsP3KB, the major enzyme producing Ins(1,3,4,5) P4 in neutrophils, augments PtdIns(3,4,5)P3 downstream signals, leading to enhanced sensitivity to chemoattractant stimulation, elevated superoxide production, and enhanced neutrophil recruitment to inflamed peritoneal cavity. nsP3KB gene is also expressed in hematopoietic stem/progenitor cells. In InsP3KB null mice, the bone marrow granulocyte monocyte progenitor (GMP) population is expanded and the proliferation of GMP cells is accelerated. As results, neutrophil production in the bone marrow is enhanced and peripheral blood neutrophil count is elevated. Ins(1,3,4,5)P4 also plays a role in maintaining neutrophil survival. Depletion of Ins(1,3,4,5)P4 leads to accelerated neutrophil spontaneous death. Finally, InsP3KB and Ins(1,3,4,5)P4 are essential components in bacterial killing by neutrophils. Despite of the augmented neutrophil recruitment, the clearance of bacteria in the InsP3KB knockout mice is significantly impaired. Collectively, these findings establish InsP3KB and its product Ins(1,3,4,5)P4 as essential modulators of neutrophil function and innate immunity
Disciplines :
Biochemistry, biophysics & molecular biology
Genetics & genetic processes
Author, co-author :
Jia, Y.;  Harvard Medical School, Dana-Farber/Harvard Cancer Center > Department of Pathology
Schurmans, Stéphane  ;  Université de Liège - ULiège > Département de sciences fonctionnelles > Biochimie métabolique vétérinaire
Luo, H. R.;  Harvard Medical School ; Dana-Farber/Harvard Cancer Center ; Department of Laboratory Medicine ; Children’s Hospital Boston > Department of Pathology
Language :
English
Title :
Regulation of innate immunity by inositol 1,3,4,5-tetrakisphosphate
Publication date :
2008
Journal title :
Cell Cycle
ISSN :
1538-4101
eISSN :
1551-4005
Publisher :
Landes Bioscience, Georgetown, United States - Texas
Volume :
7
Pages :
2803-2808
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Abbreviations: InsP3K, inositol trisphosphate kinases; GMP, granulocyte monocyte progenitor; PtdIns(3,4,5)P3, phosphatidylinositol 3,4,5 trisphosphate; PTEN, phosphatase and tensin homologue deleted on chromosome ten
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