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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Soluble ecto-5'-nucleotidase (5'-NT), alkaline phosphatase, and adenosine deaminase (ADA1) activities in neonatal blood favor elevated extracellular adenosine
Journal of Biological Chemistry, Volume 288, No. 38, Year 2013
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Description
Extracellular adenosine, a key regulator of physiology and immune cell function that is found at elevated levels in neonatal blood, is generated by phosphohydrolysis of adenine nucleotides released from cells and catabolized by deamination to inosine. Generation of adenosine monophosphate (AMP) in blood is driven by cell-associated enzymes, whereas conversion of AMP to adenosine is largely mediated by soluble enzymes. The identities of the enzymes responsible for these activities in whole blood of neonates have been defined in this study and contrasted to adult blood. We demonstrate that soluble 5'-nucleotidase (5'-NT) and alkaline phosphatase (AP) mediate conversion of AMP to adenosine, whereas soluble adenosine deaminase (ADA) catabolizes adenosine to inosine. Newborn blood plasma demonstrates substantially higher adenosine-generating 5'-NT and AP activity and lower adenosine-metabolizing ADA activity than adult plasma. In addition to a role in soluble purine metabolism, abundant AP expressed on the surface of circulating neonatal neutrophils is the dominant AMPase on these cells. Plasma samples from infant observational cohorts reveal a relative plasma ADA deficiency at birth, followed by a gradual maturation of plasma ADA through infancy. The robust adenosine-generating capacity of neonates appears functionally relevant because supplementation with AMP inhibited whereas selective pharmacologic inhibition of 5'-NT enhanced Toll-like receptor-mediated TNF-α production in neonatal whole blood. Overall, we have characterized previously unrecognized age-dependent expression patterns of plasma purine-metabolizing enzymes that result in elevated plasma concentrations of anti-inflammatory adenosine in newborns. Targeted manipulation of purine-metabolizing enzymes may benefit this vulnerable population. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3779727/bin/supp_288_38_27315__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3779727/bin/supp_M113.484212_jbc.M113.484212-1.pdf
Authors & Co-Authors
Pettengill, Matthew Aaron
United States, Boston
Boston Children's Hospital
United States, Boston
Harvard Medical School
Robson, Simon Christopher
United States, Boston
Harvard Medical School
United States, Boston
Beth Israel Deaconess Medical Center
Tresenriter, Megan
United States, Boston
Boston Children's Hospital
Millán, José Luis San
United States, San Diego
Sanford Burnham Prebys Medical Discovery Institute
Usheva, Anny A.
United States, Boston
Harvard Medical School
United States, Boston
Beth Israel Deaconess Medical Center
Bingham, Taiese
United States, Boston
Boston Children's Hospital
United States, Boston
Harvard Medical School
Belderbos, Mirjam E.
Netherlands, Utrecht
University Medical Center Utrecht
Bergelson, Ilana
United States, Boston
Boston Children's Hospital
Burl, Sarah
Gambia, Banjul
Medical Research Council Laboratories Gambia
United Kingdom, London
Imperial College London
Kampmann, Beate B.
Gambia, Banjul
Medical Research Council Laboratories Gambia
United Kingdom, London
Imperial College London
Gelinas, Laura
Canada, Vancouver
The University of British Columbia
Kollmann, Tobias R.
Canada, Vancouver
The University of British Columbia
Bont, Louis J.
Netherlands, Utrecht
University Medical Center Utrecht
Levy, Ofer
United States, Boston
Boston Children's Hospital
United States, Boston
Harvard Medical School
Statistics
Citations: 75
Authors: 14
Affiliations: 8
Identifiers
Doi:
10.1074/jbc.M113.484212
ISSN:
00219258
e-ISSN:
1083351X
Research Areas
Maternal And Child Health
Study Design
Cross Sectional Study
Cohort Study