| 1. |
- Thorlacius, Karin, et al.
(författare)
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Protective effect of fasudil, a Rho-kinase inhibitor, on chemokine expression, leukocyte recruitment, and hepatocellular apoptosis in septic liver injury.
- 2006
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Ingår i: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 1938-3673 .- 0741-5400. ; 79:5, s. 923-931
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Tidskriftsartikel (refereegranskat)abstract
- Rho-kinase signaling regulates important features of inflammatory reactions. Herein, we investigated the effect and mechanisms of action of the Rho-kinase inhibitor fasudil in endotoxemic liver injury. C57/BL/6 mice were challenged with lipopolysaccharide (LPS) and D-galactosamine, with or without pretreatment with the Rho-kinase inhibitor fasudil. Six hours after endotoxin challenge, leukocyte-endothelium interactions in the hepatic microvasculature were studied by use of intravital fluorescence microscopy and tumor necrosis factor {alpha} (TNF-{alpha}); CXC chemokines as well as liver enzymes and apoptosis were determined. Administration of fasudil reduced LPS-induced leukocyte adhesion in postsinusoidal venules and sequestration in sinusoids. Moreover, we found that fasudil abolished extravascular infiltration of leukocytes as well as production of TNF-{alpha} and CXC chemokines in the liver of endotoxemic mice. Liver enzymes and hepatocellular apoptosis were markedly reduced, and sinusoidal perfusion was improved significantly in endotoxemic mice pretreated with fasudil. Our novel data document that fasudil is a potent inhibitor of endotoxin-induced expression of TNF-{alpha} and CXC chemokines as well as leukocyte infiltration and hepatocellular apoptosis in the liver. Based on the present findings, it is suggested that inhibition of the Rho-kinase signaling pathway may be a useful target in the treatment of septic liver injury.
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| 3. |
- Hakansson, A, et al.
(författare)
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Rose Hip and Lactobacillus plantarum DSM 9843 Reduce Ischemia/Reperfusion Injury in the Mouse Colon.
- 2006
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Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; 51:11, s. 2094-2101
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Tidskriftsartikel (refereegranskat)abstract
- schaemia/reperfusion (I/R) of the colon is an inflammatory condition that leads to tissue injury where reactive oxygen species play a central role. Rose hip is rich in biologically active polyphenols with antioxidative properties, which may be important in prevention of lipid peroxidation. L. plantarum DSM 9843 possesses enzymatic activity towards polyphenols. The objective of this study was to define the effect of oral administration of L. plantarum and rose hip in I/R injury. Administration of rose hip and L. plantarum significantly decreased MDA levels in caecum tissue and Enterobacteriaceae counts in caecum stool. A positive correlation between MDA levels and Enterobacteriaceae counts was found. The results support a synergistic/additive role of rose hip and L. plantarum in reducing lipid peroxidation. Therefore rose hip and L. plantarum may be used as a pretreatment to tissue injuries, e.g. colonic surgery, organ transplantation and vascular surgery.
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| 5. |
- Sato, T, et al.
(författare)
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Short-term homing assay reveals a critical role for lymphocyte function-associated antigen-1 in the hepatic recruitment of lymphocytes in graft-versus-host disease
- 2006
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Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278. ; 44:6, s. 1132-1140
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: The liver is a major target organ of graft versus host disease (GvHD) with massive infiltration of alloreactive lymphocytes resulting in hepatitis and hepatocyte injury. Although adhesive mechanisms have been implicated in the biology of GvHD hepatitis, the identity of homing receptors involved in the initial recruitment of cells from the blood is not known. Methods: We have developed a short-term homing assay in a model of murine GvHD. Splenocytes from donors at an active stage of GvHD were injected intravenously into adoptive recipients also undergoing GvHD. The recruitment of cells to the liver was assessed 6 h after cell transfer. Results: Activated donor CD8 and CD4 lymphocytes expressed lymphocyte function antigen-1 (LITA-1), alpha 4-integrins, and P-selectin binding ligands, and localized more efficiently than naive T cells. Immunoneutralization of LFA-1 reduced the recruitment of CD8 and CD4 lymphocytes to the liver by more than 60%. Anti-LFA-1 antibody also markedly reduced infiltration of lymphocytes in periportal areas and protected against hepatocellular damage. Conclusions: We demonstrate a critical role of LFA-1 in the recruitment of activated lymphocytes to the liver and in immune-cell mediated hepatitis. LFA-1 may be an effective therapeutic target for protecting the liver following bone marrow transplantation. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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| 6. |
- Schramm, R, et al.
(författare)
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The cervical lymph node preparation: A novel approach to study lymphocyte homing by intravital microscopy
- 2006
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Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 55:4, s. 160-167
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Lymphocyte recirculation constitutes an integral part of the adaptive immune system. Blood-borne lymphocytes migrate into secondary lymphoid organs, crossing the vascular wall of site-specific high endothelial venules (HEVs). We created a preparation of the cervical lymph node in mice to study lymphocyte homing in vivo. Methods and Results: Our novel approach allowed the detailed analysis of hemodynamics and lymphocyte-HEV endothelium interactions by means of intravital fluorescence microscopy. We confirm the key roles of L-selectin and LFA-1 for lymphocyte homing. Blockade of L-selectin function inhibited lymphocyte rolling and firm adhesion by 92 % and 66%. In LFA-1-deficient mice, lymphocyte firm adhesion was reduced by 70%. In addition to the microcirculation studies, the cervical lymph node preparation allowed for visualization of afferent lymphatic transport, which is mainly derived from the oral mucosa. Conclusion: This study reports a novel technical tool for the detailed in vivo analysis of adaptive immune responses.
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