title: Neurotensin increases mortality and mast cells reduce neurotensin levels in a mouse model of sepsis.
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.
authors: Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors: Adrian M
authors: AM
authors: Piliponsky
authors: Ching-Cheng
authors: CC
authors: Chen
authors: Toshihiko
authors: T
authors: Nishimura
authors: Martin
authors: M
authors: Metz
authors: Eon J
authors: EJ
authors: Rios
authors: Paul R
authors: PR
authors: Dobner
authors: Etsuko
authors: E
authors: Wada
authors: Keiji
authors: K
authors: Wada
authors: Sherma
authors: S
authors: Zacharias
authors: Uma M
authors: UM
authors: Mohanasundaram
authors: James D
authors: JD
authors: Faix
authors: Magnus
authors: M
authors: Abrink
authors: Gunnar
authors: G
authors: Pejler
authors: Ronald G
authors: RG
authors: Pearl
authors: Mindy
authors: M
authors: Tsai
authors: Stephen J
authors: SJ
authors: Galli
mesh_terms: D000818:Animals; D015550:Cell Degranulation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007022:Hypotension / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D008407:Mast Cells / Q000378:metabolism* / Q000502:physiology; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009496:Neurotensin / Q000037:antagonists & inhibitors / Q000097:blood / Q000172:deficiency / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D018028:Receptors, Neurotensin / Q000378:metabolism; D018805:Sepsis / Q000097:blood / Q000378:metabolism*
chemical_list: D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin; D019009:Proto-Oncogene Proteins c-kit; D008666:Metalloendopeptidases; C062316:neurolysin