Skip to main content
SLU publication database (SLUpub)

Research article2008Peer reviewedOpen access

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

Piliponsky, Adrian M.; Chen, Ching-Cheng; Nishimura, Toshihiko; Metz, Martin; Rios, Eon J.; Dobner, Paul R.; Wada, Etsuko; Wada, Keiji; Zacharias, Sherma; Mohanasundaram, Uma M.; Faix, James D.; Abrink, Magnus; Pejler, Gunnar; Pearl, Ronald G.; Tsai, Mindy; Galli, Stephen J.

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.

Published in

Nature Medicine
2008, volume: 14, number: 4, pages: 392-398

SLU Authors

UKÄ Subject classification

Animal and Dairy Science
Veterinary Science

Publication identifier

  • DOI: https://doi.org/10.1038/nm1738

Permanent link to this page (URI)

https://res.slu.se/id/publ/20807