Involvement of the neuropeptide substance P in lung inflammation induced by hepatic ischemia/reperfusion

Objective and Design: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. Materials and 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.