Please use this identifier to cite or link to this item: http://dl.umsu.ac.ir/handle/Hannan/31058
Title: Regulation of Innate Immunity by Inositol 1,3,4,5-Tetrakisphosphate
Authors: Jia, Yonghui;Schurmans, Stephane;Luo, Hongbo
Year: 2008
Publisher: Landes Bioscience
Description: 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. InsP3KB 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.
URI: http://www.ncbi.nlm.nih.gov/pubmed/18769148
http://nrs.harvard.edu/urn-3:HUL.InstRepos:13348327
Standard no: Jia, Yonghui, Stephane Schurmans, and Hongbo R. Luo. 2008. “Regulation of Innate Immunity by Inositol 1,3,4,5-Tetrakisphosphate.” Cell Cycle 7 (18) (September 15): 2803–2808. doi:10.4161/cc.7.18.6688. http://dx.doi.org/10.4161/cc.7.18.6688.
1538-4101
1551-4005
Appears in Collections:HMS Scholarly Articles

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