Department of Surgery, University of Heidelberg, Heidelberg, Germany.
J Surg Res. 2013 Oct;184(2):1070-5. doi: 10.1016/j.jss.2013.04.064. Epub 2013 May 18.
Intrahepatic leukocyte sequestration is a component of the systemic inflammatory response, and can be triggered by systemic immune dysfunction during sepsis.
To 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.
Endotoxin 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.
Endotoxemia 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.
肝内白细胞扣留是全身炎症反应的一个组成部分，可在脓毒症期间全身免疫功能障碍时被触发。
为了研究内毒素血症期间白细胞扣留随时间的变化，及其对肝功能的影响，以及特定细胞黏附分子的作用，我们通过腹腔内应用脂多糖在小鼠中诱导内毒素血症。使用荧光显微镜在诱导后的不同时间测量白细胞扣留。通过测量肝酶和组织组织学来评估肝损伤。
内毒素在肝微血管中强烈诱导白细胞扣留。这与肝损伤的诱导有关，反映在酶水平的增加和组织形态学变化上。在 CD44(-/-)小鼠中，而非在细胞间黏附分子-1（ICAM-1）(-/-)、淋巴细胞功能相关抗原-1(-/-)和巨噬细胞-1(-/-)抗原小鼠中，肝内白细胞扣留减少。在 ICAM-1(-/-)、淋巴细胞功能相关抗原-1(-/-)和巨噬细胞-1(-/-)小鼠中，白细胞扣留在后期阶段下降，但在野生型和 CD44(-/-)动物中保持稳定。CD44(-/-)小鼠中白细胞扣留减少伴随着转移酶水平的显著降低。
内毒素血症诱导稳定的窦内白细胞扣留，这有助于肝损伤。在内毒素血症的初始阶段，白细胞扣留依赖于 CD44，但不依赖于 ICAM-1 和 β2 整合素。ICAM-1 和 β2 整合素，但不是 CD44，在内毒素血症的后期稳定白细胞扣留。肝内白细胞扣留的分子调节在脓毒症中可能具有重要的治疗意义，减少肝损伤并改善免疫防御能力。
