The protective role of intestinal alkaline phosphatase in necrotizing enterocolitis.
BACKGROUND
Enterocytes produce intestinal alkaline phosphatase (iAP), which detoxifies lipopolysaccharide (LPS), a mediator in necrotizing enterocolitis (NEC) pathogenesis. We hypothesize that aberrant expression or function of iAP contributes to the pathogenesis of NEC.


METHODS
Newborn Sprague Dawley rat pups were divided into three main groups. Control pups were breast fed, while two groups were exposed to intermittent hypoxia, LPS, and formula feeding for 4 d to induce NEC. Bovine iAP, with and without the presence of LPS, was administered orally to one of the NEC groups. The intestine was harvested and used to detect alkaline phosphatase (AP) activity and protein expression. Terminal ileum sections were used to grade intestinal injury and stained for AP. Comparisons were made with adult rat duodenum.


RESULTS
Compared with adult rats, control pups expressed significantly less AP protein but had 2-fold higher AP activity. NEC pup AP activity was significantly decreased compared to controls (P < or = 0.05), which paralleled both the AP protein expression and immunofluorescence assay results. Following iAP administration, immunofluorescence, protein expression, and activity of AP were significantly increased compared with NEC pups without iAP supplementation. All NEC pups had intestinal injury grades > or = 2 on a 4-point scale, while control and iAP-treated pups had grades < 0.25 (P < 0.001).


CONCLUSIONS
Enteral administration of iAP to rat pups with experimental NEC increased AP activity levels to that of controls, and appears to protect the intestine. This opens up a new area of study in NEC pathophysiology as well as a potential novel treatment strategy to prevent the development of NEC.
Whitehouse
Jill S
JS
Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Riggle
Kevin M
KM
Purpi
David P
DP
Mayer
Alan N
AN
Pritchard
Kirkwood A
KA
Oldham
Keith T
KT
Gourlay
David M
DM
D000469:Alkaline Phosphatase / Q000378:metabolism* / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D002417:Cattle; D020345:Enterocolitis, Necrotizing / Q000201:enzymology* / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D007082:Ileum / Q000473:pathology; D007527:Isoenzymes / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007527:Isoenzymes; C415671:Akp3 protein, rat; C415670:Alpi protein, rat; D000469:Alkaline Phosphatase