| 2. |
- Li, Xiang, et al.
(författare)
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Critical role of CXC chemokines in endotoxemic liver injury in mice.
- 2004
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Ingår i: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 1938-3673 .- 0741-5400. ; 75:3, s. 443-452
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Tidskriftsartikel (refereegranskat)abstract
- Tissue accumulation of leukocytes constitutes a rate-limiting step in endotoxin-induced tissue injury. Chemokines have the capacity to regulate leukocyte trafficking. However, the role of CXC chemokines, i.e., macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC), in leukocyte recruitment, microvascular perfusion failure, cellular injury, and apoptosis in the liver remains elusive. Herein, mice were challenged with lipopolysaccharide (LPS) in combination with D-galactosamine, and intravital microscopy of the liver microcirculation was conducted 6 h later. It was found that immunoneutralization of MIP-2 and KC did not reduce LPS-induced leukocyte rolling and adhesion in postsinusoidal venules. In contrast, pretreatment with monoclonal antibodies against MIP-2 and KC abolished (83% reduction) extravascular recruitment of leukocytes in the livers of endotoxemic mice. Notably, endotoxin challenge increased the expression of CXC chemokines, which was mainly confined to hepatocytes. Moreover, endotoxin-induced increases of liver enzymes and hepatocellular apoptosis were decreased by more than 82% and 68%, respectively, and sinusoidal perfusion was restored in mice passively immunized against MIP-2 and KC. In conclusion, this study indicates that intravascular accumulation of leukocytes in the liver is independent of CXC chemokines in endotoxemic mice. Instead, our novel data suggest that CXC chemokines are instrumental in regulating endotoxin-induced transmigration and extravascular tissue accumulation of leukocytes. Indeed, these findings demonstrate that interference with MIP-2 and KC functions protects against septic liver damage and may constitute a potential therapeutic strategy to control pathological inflammation in endotoxemia.
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| 3. |
- Muhammad, Asad, et al.
(författare)
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P-Selectin and P-Selectin Glycoprotein Ligand 1 Mediate Rolling of Activated CD8+ T Cells in Inflamed Colonic Venules.
- 2009
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Ingår i: Journal of Investigative Medicine. - 1708-8267. ; 57:7, s. 765-768
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:: Activated T cells regulate inflammatory diseases in the intestinal tract; however, the adhesive mechanisms governing CD8 T-cell recruitment in the colon are not known. METHODS:: Herein, we used a graft-versus-host disease (GvHD) model to study CD8 T-cell rolling and adhesion in the large intestine by use of intravital fluorescence microscopy. Graft-versus-host disease was induced by transferring 50 x 10 allogeneic donor splenocytes from BDF1, B6, H-2b mice to recipient BDF1, H-2 mice. After 8 days, rhodamine-labeled CD8 T cells (4 x 10) from healthy and GvHD mice were injected into both healthy and GvHD recipient mice, and CD8 T-cell-endothelium interactions were studied in the colon. RESULTS:: Activated CD8 T cells from GvHD mice expressed higher levels of P-selectin ligand and decreased levels of L-selectin. Immunoneutralization of P-selectin and P-selectin glycoprotein ligand 1 reduced CD8 T-cell rolling and adhesion in inflamed colonic venules by more than 71%. Inhibition of E-selectin had no effect on GvHD-induced CD8 T-cell-endothelium interactions. CONCLUSIONS:: We conclude that P-selectin and P-selectin glycoprotein ligand 1 are dominating molecules in supporting adhesive interactions of CD8 T cells in inflamed colonic venules and may be useful targets to protect against pathological inflammation in the large bowel.
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