Secretory leukocyte protease inhibitor in mice regulates local and remote organ inflammatory injury induced by hepatic ischemia/reperfusion.
OBJECTIVE
This study identified and characterized the hepatic expression of secretory leukocyte protease inhibitor (SLPI) during hepatic ischemia and reperfusion in mice. In addition, the effects of exogenously administered and endogenous SLPI on liver and lung injury induced by hepatic ischemia and reperfusion were evaluated.


METHODS
C57BL/6 mice underwent 90 minutes of partial hepatic ischemia and 4 hours of reperfusion in the presence or absence of exogenous SLPI or neutralizing antibodies to SLPI.


RESULTS
Intravenous infusion of SLPI reduced liver and lung damage and diminished neutrophil accumulation in both organs. These effects were accompanied by reduced serum levels of tumor necrosis factor (TNF)-alpha and the CXC chemokine macrophage inflammatory protein (MIP)-2. SLPI also suppressed activation of the transcription factor NF-kappaB in liver. Hepatic ischemia and reperfusion caused increased expression of SLPI messenger RNA and SLPI protein, which was found in hepatocytes. Treatment of mice with anti-SLPI enhanced serum levels of TNF-alpha and MIP-2 and increased hepatic neutrophil accumulation and amount of liver injury.


CONCLUSIONS
These data indicate that SLPI has protective effects against hepatic ischemia/reperfusion injury and suggest that endogenous SLPI functions to regulate the hepatic inflammatory response.
Lentsch
A B
AB
Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA. albent01@ulkyvm.louisville.edu
Yoshidome
H
H
Warner
R L
RL
Ward
P A
PA
Edwards
M J
MJ
D000818:Animals; D016207:Cytokines / Q000097:blood; D007249:Inflammation / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000097:blood; D007511:Ischemia / Q000150:complications* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008102:Liver Circulation; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D015427:Reperfusion Injury / Q000150:complications* / Q000473:pathology; D053481:Secretory Leukocyte Peptidase Inhibitor
D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D053481:Secretory Leukocyte Peptidase Inhibitor; C506815:Slpi protein, mouse