Involvement of the neuropeptide substance P in lung inflammation induced by hepatic ischemia/reperfusion.
OBJECTIVE
The purpose of this study was to examine the potential role of substance P in accumulation of neutrophils in the lung following hepatic ischemia/reperfusion.


METHODS
Male C57BL/6 mice (8-10 weeks of age) were subjected to either sham surgery, partial hepatic ischemia with or without reperfusion, or intratracheal administration of saline or 1 ng substance P. Lung neutrophil accumulation was assessed by tissue content of myeloperoxidase. Activation of the transcription factor, NF-kappaB, was determined by electrophoretic mobility shift assay. Levels of substance P and macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage (BAL) fluid was measured using enzyme-linked immunosorbent assays.


RESULTS
Significant pulmonary neutrophil accumulation was observed just prior to hepatic reperfusion in association with increased BAL levels of substance P. Intratracheal administration of substance P resulted in a similar pattern of neutrophil accumulation which was associated with activation of NF-kappaB and increased BAL levels of the chemokine, MIP-2.


CONCLUSIONS
The data suggest that hepatic ischemia causes substance P release in the lung which activates NF-kappaB leading to the production of MIP-2 and accumulation of neutrophils.
Okaya
T
T
Laboratory of Trauma, Sepsis & Inflammation Research, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0558, USA.
Holthaus
R
R
Kato
A
A
Lentsch
A B
AB
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D054426:Chemokine CXCL2; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000378:metabolism*; D008099:Liver / Q000473:pathology*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015846:Monokines / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D013373:Substance P / Q000502:physiology*; D013997:Time Factors
D054426:Chemokine CXCL2; D015846:Monokines; D016328:NF-kappa B; D009479:Neuropeptides; D013373:Substance P; D009195:Peroxidase