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Neutral Endopeptidase Modulates Septic Shock a
Author(s) -
LU BAO,
GERARD NORMA P.,
JR. LEE F. KOLAKOWSKI,
FINCO ORETTA,
CARROLL MICHAEL C.,
GERARD CRAIG
Publication year - 1996
Publication title -
annals of the new york academy of sciences
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1996.tb15119.x
Subject(s) - neprilysin , enkephalinase , septic shock , chemistry , oligopeptide , acetylcholinesterase , metalloproteinase , thiorphan , enzyme , biochemistry , receptor , immunology , sepsis , biology , peptide , enkephalin , opioid
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.