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dc.contributor.authorPettengill, M
dc.contributor.authorMatute, JD
dc.contributor.authorTresenriter, M
dc.contributor.authorHibbert, J
dc.contributor.authorBurgner, D
dc.contributor.authorRichmond, P
dc.contributor.authorMillian, JL
dc.contributor.authorOzonoff, A
dc.contributor.authorStrunk, T
dc.contributor.authorCurrie, A
dc.contributor.authorLevy, O
dc.date.accessioned2021-02-04T00:43:55Z
dc.date.available2021-02-04T00:43:55Z
dc.date.issued2017-04-27
dc.identifierpii: PONE-D-16-27081
dc.identifier.citationPettengill, M., Matute, J. D., Tresenriter, M., Hibbert, J., Burgner, D., Richmond, P., Millian, J. L., Ozonoff, A., Strunk, T., Currie, A. & Levy, O. (2017). Human alkaline phosphatase dephosphorylates microbial products and is elevated in preterm neonates with a history of late-onset sepsis. PLOS ONE, 12 (4), https://doi.org/10.1371/journal.pone.0175936.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/259177
dc.description.abstractBACKGROUND: 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.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.titleHuman alkaline phosphatase dephosphorylates microbial products and is elevated in preterm neonates with a history of late-onset sepsis
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0175936
melbourne.affiliation.departmentPaediatrics (RCH)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titlePLoS One
melbourne.source.volume12
melbourne.source.issue4
dc.rights.licenseCC BY
melbourne.elementsid1205419
melbourne.contributor.authorBurgner, David
melbourne.contributor.authorRICHMOND, PETER
dc.identifier.eissn1932-6203
melbourne.accessrightsOpen Access


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