Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Med. 2008 Apr;14(4):392-8. doi: 10.1038/nm1738. Epub 2008 Mar 30.

Neurotensin increases mortality and mast cells reduce neurotensin levels in a mouse model of sepsis.

Author information

  • 1Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.

Abstract

Sepsis is a complex, incompletely understood and often fatal disorder, typically accompanied by hypotension, that is considered to represent a dysregulated host response to infection. Neurotensin (NT) is a 13-amino-acid peptide that, among its multiple effects, induces hypotension. We find that intraperitoneal and plasma concentrations of NT are increased in mice after severe cecal ligation and puncture (CLP), a model of sepsis, and that mice treated with a pharmacological antagonist of NT, or NT-deficient mice, show reduced mortality during severe CLP. In mice, mast cells can degrade NT and reduce NT-induced hypotension and CLP-associated mortality, and optimal expression of these effects requires mast cell expression of neurotensin receptor 1 and neurolysin. These findings show that NT contributes to sepsis-related mortality in mice during severe CLP and that mast cells can lower NT concentrations, and suggest that mast cell-dependent reduction in NT levels contributes to the ability of mast cells to enhance survival after CLP.

PMID:
18376408
[PubMed - indexed for MEDLINE]
PMCID:
PMC2873870
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk