| Dual roles of endogenous platelet-activating factor acetylhydrolase in a murine model of necrotizing enterocolitis. | |
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MedLine Citation:
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PMID: 20531249 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 sPLA2, 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. |
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Authors:
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Jing Lu; Marissa Pierce; Andrew Franklin; Tamas Jilling; Diana M Stafforini; Michael Caplan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Pediatric research Volume: 68 ISSN: 1530-0447 ISO Abbreviation: Pediatr. Res. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-13 Completed Date: 2010-11-30 Revised Date: 2011-09-13 |
Medline Journal Info:
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Nlm Unique ID: 0100714 Medline TA: Pediatr Res Country: United States |
Other Details:
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Languages: eng Pagination: 225-30 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Pritzker School of Medicine, University of Chicago, Evanston, IL 60201, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Alkyl-2-acetylglycerophosphocholine Esterase
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blood,
deficiency*,
genetics Analysis of Variance Animals Apoptosis / physiology Chemokine CXCL1 / metabolism Cytokines / metabolism Enterocolitis, Necrotizing / enzymology*, mortality, pathology Mice Mice, Knockout Nitric Oxide Synthase Type II / metabolism Phospholipases A2, Secretory / metabolism Platelet Activating Factor / metabolism RNA, Messenger / metabolism* Reverse Transcriptase Polymerase Chain Reaction |
| Grant Support | |
ID/Acronym/Agency:
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AI058128/AI/NIAID NIH HHS; HD37581/HD/NICHD NIH HHS; HL35828/HL/NHLBI NIH HHS; R01 DK062960-03/DK/NIDDK NIH HHS; R01 DK062960-04/DK/NIDDK NIH HHS; R01 HD037581-09/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chemokine CXCL1; 0/Cytokines; 0/Platelet Activating Factor; 0/RNA, Messenger; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 3.1.1.4/Phospholipases A2, Secretory; EC 3.1.1.47/1-Alkyl-2-acetylglycerophosphocholine Esterase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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