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.
|
Authors | Matthew Pettengill, Juan D Matute, Megan Tresenriter, Julie Hibbert, David Burgner, Peter Richmond, José Luis Millán, Al Ozonoff, Tobias Strunk, Andrew Currie, Ofer Levy |
Journal | PloS one
(PLoS One)
Vol. 12
Issue 4
Pg. e0175936
( 2017)
ISSN: 1932-6203 [Electronic] United States |
PMID | 28448526
(Publication Type: Journal Article)
|
Chemical References |
- Isoenzymes
- Lipopolysaccharides
- Phosphates
- Recombinant Proteins
- Rosaniline Dyes
- Toll-Like Receptors
- malachite green
- Alkaline Phosphatase
|
Topics |
- Alkaline Phosphatase
(blood, genetics, metabolism)
- Enzyme Assays
- Female
- Gestational Age
- Humans
- Infant
- Infant, Newborn
- Infant, Premature
- Isoenzymes
(blood, metabolism)
- Klebsiella pneumoniae
(metabolism)
- Late Onset Disorders
- Lipopolysaccharides
(metabolism)
- Male
- Phosphates
(analysis, chemistry)
- Recombinant Proteins
(isolation & purification, metabolism)
- Rosaniline Dyes
(chemistry, metabolism)
- Salmonella
(metabolism)
- Sepsis
(diagnosis, microbiology, mortality)
- Toll-Like Receptors
(agonists, metabolism)
|