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Surgery. 2002 Aug;132(2):193-9.

Recombinant human neutral endopeptidase ameliorates pancreatic elastase-induced lung injury.

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  • 1Department of Surgery, University of California, San Francisco, USA.

Abstract

BACKGROUND:

Genetic deletion of neutral endopeptidase (NEP), a cell-surface metalloprotease that degrades proinflammatory peptides, exacerbates lung injury induced by pancreatic elastase in a model of pancreatitis-associated lung injury. We tested 3 hypotheses: (1) genetic deletion of NEP prolongs lung recovery after elastase injections; (2) elastase-mediated lung injury is associated with down-regulation of NEP; and (3) pretreatment of NEP (-/-) and (+/+) animals with recombinant human NEP (rhNEP) reduces pulmonary damage in this model.

METHODS:

NEP (+/+) or (-/-) mice were injected with pancreatic elastase (0.085 U/g/dose intraperitoneally) or saline carrier at t = 0 hours and t = 1 hour. Some mice were pretreated with rhNEP (3 mg/kg intraperitoneally). Serum elastase, lung histologic score, myeloperoxidase, and NEP activities were measured at 4, 8, or 12 hours.

RESULTS:

NEP (-/-) mice had worse pulmonary inflammation at 4 and 8 hours versus (+/+) mice. Lung NEP activity was similar in elastase-treated and control (+/+) animals. Pretreatment with rhNEP reduced myeloperoxidase and improved histology at 4 hours in NEP (-/-) and (+/+) mice.

CONCLUSIONS:

Pancreatic elastase induces lung injury that is worse and prolonged in NEP (-/-) mice. Pretreatment with rhNEP ameliorates this injury. Thus, upregulation of NEP is a potential therapeutic approach for pancreatitis-associated lung injury.

PMID:
12219011
[PubMed - indexed for MEDLINE]
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