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Neurokinin-1 receptor antagonist treatment protects mice against lung injury in polymicrobial sepsis.
- Source :
-
Journal of leukocyte biology [J Leukoc Biol] 2007 Sep; Vol. 82 (3), pp. 678-85. Date of Electronic Publication: 2007 Jun 12. - Publication Year :
- 2007
-
Abstract
- Earlier work from our laboratory has suggested a role for the neuropeptide substance P (SP) in inducing lung injury in sepsis. In that study, mice lacking the preprotachykinin-A gene, which encodes for SP, were protected against lung injury in sepsis. To further substantiate the role of SP in sepsis and to study its mechanism, we have evaluated the effect of SR140333, a SP receptor antagonist, on lung injury in sepsis, which was induced in male Swiss mice by cecal ligation and puncture (CLP). Sham-operated animals received the same surgical procedure, except CLP. Vehicle or SR140333 (1 mg/kg, s.c.) was administered to CLP mice 30 min before or 1 h after the CLP. Eight hours after surgery, lung tissue was collected and analyzed for myeloperoxidase (MPO) activity, chemokines, cytokines, and adhesion molecules. The CLP procedure alone caused a significant increase in the lung levels of MIP-2, MCP-1, IL-1beta, IL-6, ICAM-1, E- and P-selectin, and MPO activity when compared with sham-operated mice. SR140333 injected 30 min before or 1 h after CLP significantly attenuated the increased lung MPO activity and levels of MIP-2, MCP-1, IL-1beta, IL-6, ICAM-1, and E- and P-selectin compared with CLP-operated mice injected with the vehicle. Histological evaluation of the lung sections further supported the beneficial effect of SR140333 on lung inflammation. Therefore, SP receptor antagonism can be a potential therapeutic target in polymicrobial sepsis, and this effect is brought about via reduction in leukocyte recruitment.
- Subjects :
- Animals
Cecum drug effects
Cecum injuries
Chemokines metabolism
Cytokines metabolism
Enzyme-Linked Immunosorbent Assay
Lung Diseases immunology
Lung Diseases metabolism
Lung Injury
Male
Mice
Neutrophils metabolism
Peroxidase pharmacology
Protein Precursors metabolism
Receptors, Neurokinin-1 genetics
Receptors, Neurokinin-1 metabolism
Sepsis immunology
Sepsis metabolism
Stereoisomerism
Tachykinins metabolism
Lung drug effects
Lung Diseases drug therapy
Neurokinin-1 Receptor Antagonists
Piperidines pharmacology
Quinuclidines pharmacology
Sepsis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0741-5400
- Volume :
- 82
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of leukocyte biology
- Publication Type :
- Academic Journal
- Accession number :
- 17565047
- Full Text :
- https://doi.org/10.1189/jlb.0407217