Abstract | AIM: MATERIAL AND METHODS: In an in vivo model (42 Wistar rats), ischemia of the left liver lobe was induced for 90 min under anesthesia with xylazine/ ketanest. Sham-operated untreated ischemic and treatment group with FTY720 (1 mg/kg body weight intravenous) were investigated. The effect of FTY on I/R injury was assessed by in vivo microscopy 30-90 min after reperfusion (perfusion rate, vessel diameter, leukocyte-endothelial cell interactions, T cell infiltration), by measurement of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), reverse transcription-polymerase chain reaction (RT-PCR) of interleukin (IL)-2, IL-6, IL-10, TNF-alpha, toll-like receptor 4 (TLR-4), and by histological investigation. RESULTS: After 30 min of reperfusion, the number of T cells in sinusoids was increased four-fold. In the FTY group, the number of T cells was reduced to an half of the number of the ischemia group. Likewise, the number of adherent leukocytes in sinusoids (150.8 +/- 10.9% of s.o.) was reduced in the treatment group (117.3 +/- 12.2%; p < 0.05 vs ischemia), leading to an improvement in perfusion rate in this group (85.0 +/- 4.6% of sham group) compared to nontreated animals (57.5 +/- 10.8%; p < 0.05). According to improved microcirculation, AST/ALT values and histological tissue damage were reduced in the therapy group. RT-PCR revealed an increased expression of IL-2, IL-6, and TLR-4 in the nontreated ischemic group. This expression was clearly reduced in the treatment group. CONCLUSION: In conclusion, FTY720 ameliorates the microcirculatory, biochemical, and histological manifestations of hepatic I/R injury by preventing T cell infiltration. These results indicate that T cells are pivotal mediators in hepatic I/R and may have important implications early after liver transplantation and in warm ischemia.
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Authors | Mathias Martin, Christina Mory, Andrea Prescher, Christian Wittekind, Martin Fiedler, Dirk Uhlmann |
Journal | Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
(J Gastrointest Surg)
Vol. 14
Issue 3
Pg. 511-9
(Mar 2010)
ISSN: 1873-4626 [Electronic] United States |
PMID | 19937475
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- Cytokines
- Receptors, Lysosphingolipid
- Toll-Like Receptor 4
- Aspartate Aminotransferases
- Alanine Transaminase
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Topics |
- Alanine Transaminase
(analysis)
- Animals
- Aspartate Aminotransferases
(analysis)
- Biomarkers
(blood)
- CD4 Lymphocyte Count
- Cytokines
(analysis)
- Disease Models, Animal
- Female
- Immunohistochemistry
- Liver Circulation
(drug effects, physiology)
- Liver Diseases
(immunology, pathology, prevention & control)
- Microcirculation
(drug effects, physiology)
- Microscopy, Fluorescence
- Random Allocation
- Rats
- Rats, Wistar
- Receptors, Lysosphingolipid
(antagonists & inhibitors)
- Reperfusion Injury
(immunology, pathology, prevention & control)
- Reverse Transcriptase Polymerase Chain Reaction
- Sensitivity and Specificity
- T-Lymphocyte Subsets
(metabolism)
- Toll-Like Receptor 4
(analysis)
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