کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4300374 | 1288419 | 2013 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: The role of β2-integrins and CD44 in intrahepatic leukocyte sequestration The role of β2-integrins and CD44 in intrahepatic leukocyte sequestration](/preview/png/4300374.png)
BackgroundIntrahepatic leukocyte sequestration is a component of the systemic inflammatory response, and can be triggered by systemic immune dysfunction during sepsis.MethodsTo examine leukocyte sequestration over time during endotoxemia, its influence on liver function, and the role of specific cell adhesion molecules, endotoxemia was induced in mice by intraperitoneal application of lipopolysaccharides. Leukocyte sequestration was measured at different times after induction using fluorescence microscopy. Liver injury was evaluated by measuring liver enzymes and tissue histology.ResultsEndotoxin induces a strong leukocyte sequestration in the liver microvasculature. This was associated with an induction of liver injury, as reflected by an increase in enzyme levels and histomorphologic changes. Intrahepatic leukocyte sequestration was reduced in CD44−/−, but not in intercellular adhesion molecule-1 (ICAM-1)−/−, lymphocyte function-associated antigen-1−/−, and macrophage-1−/− antigen mice. Leukocyte sequestration dropped in ICAM-1−/−, lymphocyte function-associated antigen-1−/−, and macrophage-1−/− mice in later stages, but remained stable in wild-type and CD44−/− animals. Reduced leukocyte sequestration in CD44−/− mice was accompanied by a significant decrease in transferase levels.ConclusionsEndotoxemia induces stable intra-sinusoidal leukocyte sequestration, which contributes to liver injury. At the initial stage of the endotoxemia, leukocyte sequestration depends on CD44 but is independent of ICAM-1 and β2-integrins. Intercellular adhesion molecule-1 and β2-integrins, but not CD44, stabilize leukocyte sequestration during the later stage of endotoxemia. The molecular modulation of intrahepatic leukocyte sequestration may have important therapeutic implications in sepsis, reducing liver injury, and improving immune defense capabilities.
Journal: Journal of Surgical Research - Volume 184, Issue 2, October 2013, Pages 1070–1075