CXC-chemokine regulation and neutrophil trafficking in hepatic ischemia-reperfusion injury in P-selectin/ICAM-1 deficient mice

<p>Abstract</p> <p>Background</p> <p>Neutrophil adhesion and migration are critical in hepatic ischemia and reperfusion injury (I/R). P-selectin and the intercellular adhesion molecule (ICAM)-1 can mediate neutrophil-endothelial cell interactions, neutrophil migration,...

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Main Authors: Crockett Elahé T, Dowlatshahi Shadi, Monson Keith M
Format: Article
Language:English
Published: BMC 2007-05-01
Series:Journal of Inflammation
Online Access:http://www.journal-inflammation.com/content/4/1/11
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spelling doaj-080b5b9cde064ef89466ee2250eea2b82020-11-24T23:28:07ZengBMCJournal of Inflammation1476-92552007-05-01411110.1186/1476-9255-4-11CXC-chemokine regulation and neutrophil trafficking in hepatic ischemia-reperfusion injury in P-selectin/ICAM-1 deficient miceCrockett Elahé TDowlatshahi ShadiMonson Keith M<p>Abstract</p> <p>Background</p> <p>Neutrophil adhesion and migration are critical in hepatic ischemia and reperfusion injury (I/R). P-selectin and the intercellular adhesion molecule (ICAM)-1 can mediate neutrophil-endothelial cell interactions, neutrophil migration, and the interactions of neutrophils with hepatocytes in the liver. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy in reperfusion injury, indicating that the length of injury might be a critical factor in neutrophil infiltration. Therefore, the aim of this study was to assess the role of P-selectin and ICAM-1 in neutrophil infiltration and liver injury during early and late phases of liver I/R.</p> <p>Methods</p> <p>Adult male wild-type and P-selectin/ICAM-1-deficient (P/I null) mice underwent 90 minutes of partial liver ischemia followed by various periods of reperfusion (6, 15 h, and a survival study). Liver injury was assessed by plasma level of alanine aminotransferase (ALT) and histopathology. The plasma cytokines, TNF-α, IL-6, MIP-2 and KC, were measured by ELISA.</p> <p>Results</p> <p>Reperfusion caused significant hepatocellular injury in both wild-type and P/I null mice as was determined by plasma ALT levels and liver histopathology. The injury was associated with a marked neutrophil infiltration into the ischemic livers of both wild-type and P/I null mice. Although the levels of ALT and neutrophil infiltration were slightly lower in the P/I null mice compared with the wild-type mice the differences were not statistically significant. The plasma cytokine data of TNF-α and IL-6 followed a similar pattern to ALT data, and no significant difference was found between the wild-type and P/I null groups. In contrast, a significant difference in KC and MIP-2 chemokine levels was observed between the wild-type and P/I null mice. Additionally, the survival study showed a trend towards increased survival in the P/I null group.</p> <p>Conclusion</p> <p>While ICAM-1 and P-selectin does not appear to be critical for neutrophil infiltration and I/R injury in the liver, they may regulate CXC-chemokine production. Blockage of these adhesion molecules may improve survival and remote organ injury that often accompanies liver I/R injury, through chemokine regulation.</p> http://www.journal-inflammation.com/content/4/1/11
collection DOAJ
language English
format Article
sources DOAJ
author Crockett Elahé T
Dowlatshahi Shadi
Monson Keith M
spellingShingle Crockett Elahé T
Dowlatshahi Shadi
Monson Keith M
CXC-chemokine regulation and neutrophil trafficking in hepatic ischemia-reperfusion injury in P-selectin/ICAM-1 deficient mice
Journal of Inflammation
author_facet Crockett Elahé T
Dowlatshahi Shadi
Monson Keith M
author_sort Crockett Elahé T
title CXC-chemokine regulation and neutrophil trafficking in hepatic ischemia-reperfusion injury in P-selectin/ICAM-1 deficient mice
title_short CXC-chemokine regulation and neutrophil trafficking in hepatic ischemia-reperfusion injury in P-selectin/ICAM-1 deficient mice
title_full CXC-chemokine regulation and neutrophil trafficking in hepatic ischemia-reperfusion injury in P-selectin/ICAM-1 deficient mice
title_fullStr CXC-chemokine regulation and neutrophil trafficking in hepatic ischemia-reperfusion injury in P-selectin/ICAM-1 deficient mice
title_full_unstemmed CXC-chemokine regulation and neutrophil trafficking in hepatic ischemia-reperfusion injury in P-selectin/ICAM-1 deficient mice
title_sort cxc-chemokine regulation and neutrophil trafficking in hepatic ischemia-reperfusion injury in p-selectin/icam-1 deficient mice
publisher BMC
series Journal of Inflammation
issn 1476-9255
publishDate 2007-05-01
description <p>Abstract</p> <p>Background</p> <p>Neutrophil adhesion and migration are critical in hepatic ischemia and reperfusion injury (I/R). P-selectin and the intercellular adhesion molecule (ICAM)-1 can mediate neutrophil-endothelial cell interactions, neutrophil migration, and the interactions of neutrophils with hepatocytes in the liver. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy in reperfusion injury, indicating that the length of injury might be a critical factor in neutrophil infiltration. Therefore, the aim of this study was to assess the role of P-selectin and ICAM-1 in neutrophil infiltration and liver injury during early and late phases of liver I/R.</p> <p>Methods</p> <p>Adult male wild-type and P-selectin/ICAM-1-deficient (P/I null) mice underwent 90 minutes of partial liver ischemia followed by various periods of reperfusion (6, 15 h, and a survival study). Liver injury was assessed by plasma level of alanine aminotransferase (ALT) and histopathology. The plasma cytokines, TNF-α, IL-6, MIP-2 and KC, were measured by ELISA.</p> <p>Results</p> <p>Reperfusion caused significant hepatocellular injury in both wild-type and P/I null mice as was determined by plasma ALT levels and liver histopathology. The injury was associated with a marked neutrophil infiltration into the ischemic livers of both wild-type and P/I null mice. Although the levels of ALT and neutrophil infiltration were slightly lower in the P/I null mice compared with the wild-type mice the differences were not statistically significant. The plasma cytokine data of TNF-α and IL-6 followed a similar pattern to ALT data, and no significant difference was found between the wild-type and P/I null groups. In contrast, a significant difference in KC and MIP-2 chemokine levels was observed between the wild-type and P/I null mice. Additionally, the survival study showed a trend towards increased survival in the P/I null group.</p> <p>Conclusion</p> <p>While ICAM-1 and P-selectin does not appear to be critical for neutrophil infiltration and I/R injury in the liver, they may regulate CXC-chemokine production. Blockage of these adhesion molecules may improve survival and remote organ injury that often accompanies liver I/R injury, through chemokine regulation.</p>
url http://www.journal-inflammation.com/content/4/1/11
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AT dowlatshahishadi cxcchemokineregulationandneutrophiltraffickinginhepaticischemiareperfusioninjuryinpselectinicam1deficientmice
AT monsonkeithm cxcchemokineregulationandneutrophiltraffickinginhepaticischemiareperfusioninjuryinpselectinicam1deficientmice
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