|Glucose-6-phosphatase-β, implicated in a congenital neutropenia syndrome, is essential for macrophage energy homeostasis and functionality.|
|PMID: 22246029 Owner: NLM Status: MEDLINE|
|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.|
|Hyun Sik Jun; Yuk Yin Cheung; Young Mok Lee; Brian C Mansfield; Janice Y Chou|
Related Documents :
|21857739 - Thrombophilia and ovarian hyperstimulation syndrome: a case report.
21943449 - Testicular pain as a presentation of cowden syndrome.
21710389 - Stepped approach for prediction of syndrome z in patients attending sleep clinic: a nor...
21631179 - Four systems involved with congenital abnormalities: a new type of syndromic hearing lo...
22134259 - Acute cranial decompression in meckel-gruber syndrome and slit-ventricle syndrome with ...
21941489 - Neuroblastoma presenting with acute kidney injury, hyponatremic-hypertensive-like syndr...
20392409 - Horner's syndrome as a co-presentation of tuberculous retropharyngeal abscess.
3588169 - Incidence of nephrotic syndrome in patients with glomerulonephritis.
3605039 - Biliary tract manifestations of the marfan syndrome.
|Type: Journal Article; Research Support, N.I.H., Intramural Date: 2012-01-12|
|Title: Blood Volume: 119 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2012 Apr|
|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|
|Languages: eng Pagination: 4047-55 Citation Subset: AIM; IM|
|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.|
|APA/MLA Format Download EndNote Download BibTex|
Calcium / metabolism
Cytokines / metabolism
Glucose / metabolism
Glucose Transporter Type 1 / genetics, metabolism
Glucose Transporter Type 3 / genetics, metabolism
Glucose-6-Phosphatase / physiology*
Glucose-6-Phosphate / metabolism*
Homeostasis / physiology*
Inflammation / genetics, metabolism, pathology*
Macrophages / cytology, physiology*
Mice, Inbred C57BL
NADPH Oxidase / genetics, metabolism
Neutropenia / congenital*, genetics, metabolism, pathology
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
|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 220.127.116.11/NADPH Oxidase; EC 18.104.22.168/neutrophil cytosolic factor 1; EC 22.214.171.124/Glucose-6-Phosphatase; EC 126.96.36.199/glucose-6-phosphatase-beta, mouse|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Engraftment of human HSCs in nonirradiated newborn NOD-scid IL2r? null mice is enhanced by transgeni...
Next Document: Overlapping and divergent signalling pathways of N- and VE-cadherin in endothelial cells.