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Journal article
Human alkaline phosphatase dephosphorylates microbial products and is elevated in preterm neonates with a history of late-onset sepsis
PLOS ONE, Vol.12(4), e0175936
2017
Abstract
Background A 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. Methods Recombinant 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). Results TNAP 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. Conclusions TNAP, 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.
Details
- Title
- Human alkaline phosphatase dephosphorylates microbial products and is elevated in preterm neonates with a history of late-onset sepsis
- Authors/Creators
- M. Pettengill (Author/Creator) - Boston Children's HospitalJ.D. Matute (Author/Creator) - Harvard UniversityM. Tresenriter (Author/Creator) - University of California, DavisJ. Hibbert (Author/Creator) - The University of Western AustraliaD. Burgner (Author/Creator) - Murdoch Children's Research InstituteP. Richmond (Author/Creator) - The University of MelbourneJ. Luis Millán (Author/Creator)A. Ozonoff (Author/Creator) - Harvard UniversityT. Strunk (Author/Creator) - The University of Western AustraliaA.J. Currie (Author/Creator) - Murdoch UniversityO. Levy (Author/Creator) - Boston Children's Hospital
- Publication Details
- PLOS ONE, Vol.12(4), e0175936
- Publisher
- Public Library of Science
- Identifiers
- 991005542684807891
- Copyright
- © 2017 Pettengill et al.
- Murdoch Affiliation
- School of Veterinary and Life Sciences
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.80 Bone Diseases
- 1.80.2081 Hypophosphatasia
- Web Of Science research areas
- Gastroenterology & Hepatology
- ESI research areas
- Clinical Medicine