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[摘要]：Background. Mechanisms mediating CD4(+) T-cell recruitment during alloantigen-independent hepatic ischemia-reperfusion (I/R) remain not fully understood. We hypothesized that Kupffer cells activate CD4(+) T-cells in the postischemic liver, by the release of free oxygen radicals and cytokines.Methods. Recruitment of freshly isolated and fluorescence-labeled CD4(+) T-cell was analyzed after hepatic I/R (90/30-120 min) using intravital microscopy in sham-operated mice, in mice after hepatic I/R and in postischemic groups after Kupffer cell depletion, after treatment with antioxidant glutathione, in interleukin (IL)-6-/- mice; and in wild-type mice after infusion of tumor necrosis factor (TNF) receptor-1-/-CD4+ T-cells. Using flow cytometry and immunohistochemistry, we assessed whether Kupffer cell-derived mediators activate CD4(+) T-cells and sinusoidal endothelial cells. The clearance kinetics of fluorescence-labeled latex beads was determined as a marker of Kupffer cell activity in vivo.Results. I/R-induced accumulation of CD4(+) T-cells in hepatic sinusoids was significantly attenuated on Kupffer cell depletion, after scavenging of free radicals and after interruption of the IL-6- and TNF-alpha-dependent pathways. These mediators directly activate CD4(+) T-cells and up-regulated the expression of T cell-relevant adhesion molecules on sinusoidal endothelial cells. Postischemic activity of Kupffer cells was significantly impaired in wild-type mice, and was even more depressed in CD4-/- animals.Conclusion. Kupffer cells trigger recruitment of CD4(+) T-cells in the postischemic liver by the release of reactive oxygen species, IL-6, and TNF-alpha. These mediators are capable of activating CD4(+) T-cells and sinusoidal endothelial cells. CD4(+) T-cells, in turn, influence the activation of Kupffer cells. |
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