Neurotensin increases mortality and mast cells reduce neurotensin levels in a mouse model of sepsis
2008 (English)In: Nature Medicine, ISSN 1078-8956, Vol. 14, no 4, 392-398 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2008. Vol. 14, no 4, 392-398 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-98895DOI: 10.1038/nm1738ISI: 000254674100025PubMedID: 18376408OAI: oai:DiVA.org:uu-98895DiVA: diva2:201494