Dual roles of endogenous platelet-activating factor acetylhydrolase in a murine model of necrotizing enterocolitis

Academic Article

Abstract

  • Human preterm infants with necrotizing enterocolitis (NEC) have increased circulating and luminal levels of platelet-activating factor (PAF) and decreased serum PAF-acetylhydrolase (PAF-AH), the enzyme that inactivates PAF. Formula supplemented with recombinant PAF-AH decreases NEC in a neonatal rat model. We hypothesized that endogenous PAF-AH contributes to neonatal intestinal homeostasis and therefore developed PAF-AH -/- mice using standard approaches to study the role of this enzyme in the neonatal NEC model. After exposure to a well-established NEC model, intestinal tissues were evaluated for histology, proinflammatory cytokine mRNA synthesis, and death using standard techniques. We found that mortality rates were significantly lower in PAF-AH -/- pups compared with wild-type controls before 24 h of life but surviving PAF-AH -/- animals were more susceptible to NEC development compared with wild-type controls. Increased NEC incidence was associated with prominent inflammation characterized by elevated intestinal mRNA expression of sPLA 2, inducible NOS, and CXCL1. In conclusion, the data support a protective role for endogenous PAF-AH in the development of NEC, and because preterm neonates have endogenous PAF-AH deficiency, this may place them at increased risk for disease. © 2010 International Pediatric Research Foundation, Inc.
  • Published In

  • Pediatric Research  Journal
  • Digital Object Identifier (doi)

    Author List

  • Lu J; Pierce M; Franklin A; Jilling T; Stafforini DM; Caplan M
  • Start Page

  • 225
  • End Page

  • 230
  • Volume

  • 68
  • Issue

  • 3