Document Detail


Glucose-6-phosphatase-β, implicated in a congenital neutropenia syndrome, is essential for macrophage energy homeostasis and functionality.
MedLine Citation:
PMID:  22246029     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glucose-6-phosphatase-β (G6Pase-β or G6PC3) deficiency, also known as severe congenital neutropenia syndrome 4, is characterized not only by neutropenia but also by impaired neutrophil energy homeostasis and functionality. We now show the syndrome is also associated with macrophage dysfunction, with murine G6pc3(-/-) macrophages having impairments in their respiratory burst, chemotaxis, calcium flux, and phagocytic activities. Consistent with a glucose-6-phosphate (G6P) metabolism deficiency, G6pc3(-/-) macrophages also have a lower glucose uptake and lower levels of G6P, lactate, and ATP than wild-type macrophages. Furthermore, the expression of NADPH oxidase subunits and membrane translocation of p47(phox) are down-regulated, and G6pc3(-/-) macrophages exhibit repressed trafficking in vivo both during an inflammatory response and in pregnancy. During pregnancy, the absence of G6Pase-β activity also leads to impaired energy homeostasis in the uterus and reduced fertility of G6pc3(-/-) mothers. Together these results show that immune deficiencies in this congenital neutropenia syndrome extend beyond neutrophil dysfunction.
Authors:
Hyun Sik Jun; Yuk Yin Cheung; Young Mok Lee; Brian C Mansfield; Janice Y Chou
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2012-01-12
Journal Detail:
Title:  Blood     Volume:  119     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-27     Completed Date:  2012-07-12     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4047-55     Citation Subset:  AIM; IM    
Affiliation:
Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Blotting, Western
Calcium / metabolism
Cell Proliferation
Chemotaxis
Cytokines / metabolism
Female
Glucose / metabolism
Glucose Transporter Type 1 / genetics,  metabolism
Glucose Transporter Type 3 / genetics,  metabolism
Glucose-6-Phosphatase / physiology*
Glucose-6-Phosphate / metabolism*
Homeostasis / physiology*
Immunoenzyme Techniques
Inflammation / genetics,  metabolism,  pathology*
Macrophages / cytology,  physiology*
Mice
Mice, Inbred C57BL
Mice, Knockout
NADPH Oxidase / genetics,  metabolism
Neutropenia / congenital*,  genetics,  metabolism,  pathology
Phagocytosis
Pregnancy
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Respiratory Burst
Signal Transduction
Syndrome
Chemical
Reg. No./Substance:
0/Cytokines; 0/Glucose Transporter Type 1; 0/Glucose Transporter Type 3; 0/RNA, Messenger; 0/Slc2a1 protein, mouse; 0/Slc2a3 protein, mouse; 50-99-7/Glucose; 56-73-5/Glucose-6-Phosphate; 7440-70-2/Calcium; EC 1.6.3.1/NADPH Oxidase; EC 1.6.3.1/neutrophil cytosolic factor 1; EC 3.1.3.9/Glucose-6-Phosphatase; EC 3.1.3.9/glucose-6-phosphatase-beta, mouse
Comments/Corrections

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