Evidence map›Paper›PMID 23897810›Full record

Trial reportThe Journal of biological chemistry2013

Soluble ecto-5'-nucleotidase (5'-NT), alkaline phosphatase, and adenosine deaminase (ADA1) activities in neonatal blood favor elevated extracellular adenosine.

Matthew Pettengill, Simon Robson, Megan Tresenriter, José Luis Millán, Anny Usheva, Taiese Bingham, Mirjam Belderbos, Ilana Bergelson, Sarah Burl, Beate Kampmann and 4 more

Open access · hybridAbstract readClinical Trial
In one paragraph

Trial report in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
7.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 90 citations in OpenAlex.

  1. Trial
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  3. Hypophosphatasia-pathophysiological understanding, preclinical data looking beyond the skeleton, and upcoming treatments.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 7 institutions in 5 countries.

Matthew PettengillDepartment of Medicine, Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts 02115; Harvard Medical School, Boston, Massachusetts 02115.
Simon RobsonHarvard Medical School, Boston, Massachusetts 02115; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215.
Megan TresenriterDepartment of Medicine, Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts 02115.
José Luis MillánSanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California 92037.
Anny UshevaHarvard Medical School, Boston, Massachusetts 02115; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215.
Taiese BinghamDepartment of Medicine, Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts 02115; Harvard Medical School, Boston, Massachusetts 02115.
Mirjam BelderbosDepartment of Pediatrics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Ilana BergelsonDepartment of Medicine, Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts 02115.
Sarah BurlVaccinology Theme Group, Medical Research Council Unit, Fajara, The Gambia; Department of Pediatrics, Imperial College London, London W2 IPG, United Kingdom.
Beate KampmannVaccinology Theme Group, Medical Research Council Unit, Fajara, The Gambia; Department of Pediatrics, Imperial College London, London W2 IPG, United Kingdom.
Laura GelinasExperimental Medicine Program, Department of Medicine.
Tobias KollmannDivision of Infectious and Immunologic Diseases, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
Louis BontDepartment of Pediatrics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Ofer LevyDepartment of Medicine, Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts 02115; Harvard Medical School, Boston, Massachusetts 02115. Electronic address: ofer.levy@childrens.harvard.edu.
Boston Children's Hospital · USHarvard University · USImperial College London · GBUniversity Medical Center Utrecht · NLBeth Israel Deaconess Medical Center · USSanford Burnham Prebys Medical Discovery Institute · USUniversity of British Columbia · CA

Funding

INFECTIOUS DISEASE AND BASIC MICROBIOLOGICAL MECHANISMST32AI007061 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Marcia B Goldberg · 1985 to 2026
$12.1M
MOLECULAR PATHOGENESIS/TREATMENT OF HYPOPHOSPHATASIAR01DE012889 · NIDCR · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MILLAN, JOSE LUIS · 1999 to 2020
$9.2M
Thrombus Formation In VivoP01HL087203 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI FURIE, BRUCE · 2008 to 2012
$8.8M
Mechanisms of initiation of skeletal mineralizationR01AR053102 · NIAMS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MILLAN, JOSE LUIS · 2006 to 2015
$3.8M
Pediatric Infectious Diseases Research TrainingT32HD055148 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI WESSELS, MICHAEL R · 2008 to 2018
$2.7M
YY1 FUNCTIONS IN VASCULAR SMOOTH MUSCLE CELLSR01HL062458 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI USHEVA-SIMIDJIYSKA, ANNY · 2000 to 2008
$2.6M
Modeling distinct neonatal purine metabolism to inform vaccine developmentR01AI100135 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI LEVY, OFER · 2012 to 2016
$2.5M
Purinergic ThromboregulationR01HL094400 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI ROBSON, SIMON C. · 2009 to 2010
$1.4M
Engineering Inhibitory Antibodies to Ectoenzymes for Cancer TreatmentR21CA164970 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI ROBSON, SIMON C. · 2012 to 2013
$405k
IMMUNE FUNCTION AND BIODEFENSE IN CHILDREN. ELDERLY AND IMMUNOCOMPROMI-266050023N01AI050023 · NIAID · UNIVERSITY OF WASHINGTON · PI WILSON, CHRISTOPHER · 2006 to 2006
–
CIHRMedical Research Council MC_UP_A900_1115Medical Research Council MC_UP_A900_1122NCI NIH HHS R21 CA164970NHLBI NIH HHS P01 HL087203NHLBI NIH HHS R01 HL062458NHLBI NIH HHS R01 HL094400NIAID NIH HHS 1R01AI100135-01NIAID NIH HHS N01 AI050023NIAID NIH HHS R01 AI100135NIAID NIH HHS T32 AI007061NIAMS NIH HHS R01 AR053102NICHD NIH HHS T32 HD055148NIDCR NIH HHS R01 DE012889
6 · The paper itself

Abstract

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.

Indexed as

5'-NucleotidaseAdenosineAdenosine DeaminaseAdultAgingAlkaline PhosphataseFemaleGene Expression Regulation, EnzymologicHumansInfant, NewbornInosineMale5'-NucleotidaseADA protein, humanAdenosineAdenosine DeaminaseAlkaline PhosphataseInosineAdenosineAdenosine ReceptorADPAMPATPImmunologyInfectious DiseasesInnate ImmunityPurinePurinergic Agonists

Identifiers

PMID23897810
PMCPMC3779727
OpenAlexW1987974483

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.