Neutral endopeptidase modulates septic shock

Ann N Y Acad Sci. 1996 Mar 22;780:156-63. doi: 10.1111/j.1749-6632.1996.tb15119.x.

Abstract

Neutral endopeptidase (NEP; EC 3.4.24.11) is a type-2 cell-surface metalloproteinase known by a variety of eponyms, including enkephalinase, common acute lymphoblastic leukemia antigen (CALLA), and CD10. Identified substrates are largely neural or humoral oligopeptide agonists, and the enzyme functions to terminate signaling by degrading the ligand, analogous to the acetylcholine/acetylcholinesterase system. Targeted disruption of the NEP locus in mice results in enhanced lethality to endotoxin shock with a pronounced gene-dosage effect. The site(s) of action appears downstream from release of TNF and IL-1, as NEP-deficient animals demonstrate increased sensitivity to these mediators as well. This unexpected finding indicates an important protective role for NEP in septic shock.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Toxins
  • Endotoxins
  • Female
  • Gene Targeting
  • Genomic Library
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Neprilysin / genetics
  • Neprilysin / metabolism*
  • Regression Analysis
  • Salmonella enteritidis
  • Shock, Septic / enzymology*
  • Shock, Septic / prevention & control

Substances

  • Bacterial Toxins
  • Endotoxins
  • salmonella toxin
  • Neprilysin