Article abstract
Nature Medicine 14, 392 - 398 (2008)
Published online: 30 March 2008 | doi:10.1038/nm1738
Neurotensin increases mortality and mast cells reduce neurotensin levels in a mouse model of sepsis
Adrian M Piliponsky1, Ching-Cheng Chen1,12, Toshihiko Nishimura2,12, Martin Metz3,4, Eon J Rios1, Paul R Dobner5, Etsuko Wada6,7, Keiji Wada6,7, Sherma Zacharias8, Uma M Mohanasundaram8, James D Faix1, Magnus Abrink9, Gunnar Pejler10, Ronald G Pearl8, Mindy Tsai1 & Stephen J Galli1,11
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.
- Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
- Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, California 94305, USA.
- Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité-Universitätsmedizin Berlin, D-10117 Berlin, Germany.
- Department of Dermatology, University Hospital Mainz, 55131 Mainz, Germany.
- Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA.
- Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
- CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 322-0012, Japan.
- Department of Anesthesiology, Stanford University School of Medicine, Stanford, California 94305, USA.
- Department of Medical Biochemistry and Microbiology, Uppsala University, SE-751 05 Uppsala, Sweden.
- Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden.
- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA.
- These authors contributed equally to this work.
Correspondence to: Stephen J Galli1,11 e-mail: sgalli@stanford.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
Parametric Images of the Extrastriatal D2 Receptor Density Obtained Using a High-Affinity Ligand (FLB 457) and a Double-Saturation MethodJournal of Cerebral Blood Flow & Metabolism Original Article
Mutations in PROP1 cause familial combined pituitary hormone deficiencyNature Genetics Letter (01 Feb 1998)
The mouse pudgy mutation disrupts Delta homologue Dll3 and initiation of early somite boundariesNature Genetics Letter (01 Jul 1998)
IL-15 constrains mast cell?dependent antibacterial defenses by suppressing chymase activitiesNature Medicine Article (01 Aug 2007)
See all 8 matches for Research
