The role of recombinant platelet-activating factor acetylhydrolase in a neonatal rat model of necrotizing enterocolitis.
Previous studies have shown that the endogenous inflammatory mediator platelet-activating factor (PAF) plays an important role in the pathophysiology of neonatal necrotizing enterocolitis (NEC). This study was designed to investigate the role of the PAF-degrading enzyme acetylhydrolase (PAF-AH) in a neonatal rat model of NEC. To study the absorption, localization, and activity of human recombinant PAF-AH (rPAF-AH), newborn rats were treated with enteral rPAF-AH, and plasma and intestines were sampled at 8 and 24 h for determination of PAF-AH enzyme activity and rPAF-AH concentration using a specific enzyme-linked immunoassay. To study the effect of rPAF-AH on neonatal NEC, rats were treated with rPAF-AH via the enteral route every 3 h, and then subjected to formula feeding and asphyxia per an established neonatal rat protocol for NEC. Pretreatment with enteral rPAF-AH significantly reduced the incidence of NEC compared with controls (6/26 versus 19/26, p < 0.001). We found that enteral rPAF-AH administration resulted in significant intestinal PAF-AH activity but no circulating PAF-AH activity despite immunohistochemical localization of the administered rPAF-AH to the intestinal epithelial cells. These findings suggest that rPAF-AH is functional and stable in the gut of neonatal rats. We conclude that enteral administration of rPAF-AH remains locally active and reduces the incidence of NEC in our experimental animal model.
Caplan
M S
MS
Department of Pediatrics, Evanston Hospital, Northwestern University Medical School, Illinois 60201, USA.
Lickerman
M
M
Adler
L
L
Dietsch
G N
GN
Yu
A
A
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004761:Enterocolitis, Pseudomembranous / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D010741:Phospholipases A / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism
D011994:Recombinant Proteins; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase