Evidence map›Paper›PMID 28448526›Full record

ArticlePloS one2017

Human alkaline phosphatase dephosphorylates microbial products and is elevated in preterm neonates with a history of late-onset sepsis.

Matthew Pettengill, Juan D Matute, Megan Tresenriter, Julie Hibbert, David Burgner, Peter Richmond, José Luis Millán, Al Ozonoff, Tobias Strunk, Andrew Currie and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

28 citing papers in PubMed, 43 citations in OpenAlex.

  1. Trial
  2. Article
  3. Bone turnover markers in the management of CKD-associated osteoporosis-a European consensus.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026
    Review
  4. 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
    Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. BECC-engineered live-attenuatedResearch square · 2024
    Article
  10. Article
  11. Review
  12. Article
  13. Observational
  14. Review
  15. TNAP: A New Multitask Enzyme in Energy Metabolism.International journal of molecular sciences · 2021
    Review
  16. Article
  17. Article
  18. Hypophosphatasia: A Unique Disorder of Bone Mineralization.International journal of molecular sciences · 2021
    Review
  19. TNAP as a New Player in Chronic Inflammatory Conditions and Metabolism.International journal of molecular sciences · 2021
    Review
  20. Observational
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 8 institutions in 2 countries.

Matthew PettengillPrecision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts, United States of America.
Juan D MatuteHarvard Medical School, Boston, Massachusetts, United States of America.
Megan TresenriterUniversity of California Davis School of Medicine, Davis, California, United States of America.
Julie HibbertThe University of Western Australia, Crawley, Western Australia, Australia.
David BurgnerMurdoch Children's Research Institute, Parkville, Victoria, Australia.
Peter RichmondDepartment of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.
José Luis MillánSanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, LaJolla, California, United States of America.
Al OzonoffHarvard Medical School, Boston, Massachusetts, United States of America.
Tobias StrunkThe University of Western Australia, Crawley, Western Australia, Australia.
Andrew CurrieThe University of Western Australia, Crawley, Western Australia, Australia.
Ofer LevyPrecision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts, United States of America.
Boston Children's Hospital · USHarvard University · USUniversity of Western Australia · AUMurdoch Children's Research Institute · AUMurdoch University · AUSanford Burnham Prebys Medical Discovery Institute · USUniversity of California, Davis · USUniversity of Melbourne · AU

Funding

MOLECULAR PATHOGENESIS/TREATMENT OF HYPOPHOSPHATASIAR01DE012889 · NIDCR · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MILLAN, JOSE LUIS · 1999 to 2020
$9.2M
Pediatric Infectious Diseases Research TrainingT32HD055148 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI WESSELS, MICHAEL R · 2008 to 2018
$2.7M
Modeling distinct neonatal purine metabolism to inform vaccine developmentR01AI100135 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI LEVY, OFER · 2012 to 2016
$2.5M
Adenosine Shapes Neonatal Toll-like Receptor FunctionR01AI067353 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI LEVY, OFER · 2006 to 2010
$2.1M
NIAID NIH HHS R01 AI067353NIAID NIH HHS R01 AI100135NICHD NIH HHS T32 HD055148NIDCR NIH HHS R01 DE012889
6 · The paper itself

Abstract

backgroundA host defense function for Alkaline phosphatases (ALPs) is suggested by the contribution of intestinal ALP to detoxifying bacterial lipopolysaccharide (endotoxin) in animal models in vivo and the elevation of ALP activity following treatment of human cells with inflammatory stimuli in vitro. However the activity of ALP in human plasma (primarily tissue-nonspecific ALP; TNAP) on lipopolysaccharide and other microbial products has not been assessed, nor has its expression been studied in preterm newborns, a vulnerable population at high risk of sepsis. In this context, the aim of our study was to characterize the activity of TNAP on Toll-like receptor (TLR) agonists and assess the concentrations of plasma ALP during late-onset sepsis in preterm newborns.

methodsRecombinant human TNAP was incubated with microbial products and phosphate release was measured by malachite green assay. Plasma ALP activity was measured serially in a cohort of preterm (N = 129) infants at high risk of late-onset sepsis (LOS).

resultsTNAP dephosphorylates poly-inosine:cytosine (Toll-like receptor (TLR) 3 agonist) and LPS from Klebsiella pneumoniae and Salmonella minnesota (TLR4 agonists). Plasma ALP significantly increased postnatally over the first 4 weeks of life in preterm and term newborns. Bacteremic LOS in preterm infants (gestational age ≤ 30 weeks) was associated with significantly elevated plasma ALP at 4 weeks postnatal age.

conclusionsTNAP, the main circulating isozyme of ALP, de-phosphorylates TLR agonists, demonstrates a post-natal age dependent increase in preterm and term plasma across the first 4 weeks of life, and is elevated in association with preterm LOS.

Indexed as

Alkaline PhosphataseEnzyme AssaysFemaleGestational AgeHumansInfantInfant, NewbornInfant, PrematureIsoenzymesKlebsiella pneumoniaeLate Onset DisordersLipopolysaccharidesMalePhosphatesRecombinant ProteinsRosaniline DyesAlkaline PhosphataseIsoenzymesLipopolysaccharidesmalachite greenPhosphatesRecombinant ProteinsRosaniline DyesToll-Like Receptors

Identifiers

PMID28448526
PMCPMC5407836
OpenAlexW2610062256

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.