Kato Takashi, Sato Yoshinobu, Takahashi Satoshi, Kawamura Hiroki, Hatakeyama Katsuyoshi, Abo Toru
First Department of Surgery, Niigata University School of Medicine, Niigata, Japan.
J Hepatol. 2004 Feb;40(2):285-90. doi: 10.1016/j.jhep.2003.10.017.
BACKGROUND/AIMS: Natural killer T (NKT) cells are present in the liver of mice. We examined whether NKT cells and other leukocytes were associated with hepatic inflammation after partial hepatectomy.
Approximately 70% of the liver was removed from mice using the method described by Higgins and Anderson.
Partial hepatectomy induced the expansion of NKT cells in the liver and the elevation of transaminase. These responses were completely suppressed by the administration of tacrolimus. NKT cell-deficient mice showed a decreased level of transaminase after partial hepatectomy. Perforin (-/-) mice showed an elevation of transaminase while B6-gld/gld mice (Fas ligand-) showed a decreased elevation of transaminase. In TAP-1(-/-) mice which lacked CD8+ cytotoxic T cells, inflammation remained at a normal level after partial hepatectomy. Since NKT cell-deficient mice showed up to 50% decrease in the level of inflammation, we examined the association of other leukocytes with the remaining inflammation. The number and proportion of granulocytes were increased by partial hepatectomy.
Both NKT cells and granulocytes participated in the hepatic inflammation after partial hepatectomy. The function of NKT cells, but not of granulocytes, was found to be sensitive to the immunosuppressive effect of tacrolimus.
背景/目的:自然杀伤T(NKT)细胞存在于小鼠肝脏中。我们研究了部分肝切除术后NKT细胞和其他白细胞是否与肝脏炎症有关。
采用希金斯和安德森描述的方法从小鼠体内切除约70%的肝脏。
部分肝切除术导致肝脏中NKT细胞扩增和转氨酶升高。这些反应被给予他克莫司完全抑制。NKT细胞缺陷小鼠在部分肝切除术后转氨酶水平降低。穿孔素(-/-)小鼠转氨酶升高,而B6-gld/gld小鼠(Fas配体缺陷)转氨酶升高程度降低。在缺乏CD8+细胞毒性T细胞的TAP-1(-/-)小鼠中,部分肝切除术后炎症仍维持在正常水平。由于NKT细胞缺陷小鼠的炎症水平降低了50%,我们研究了其他白细胞与剩余炎症的关系。部分肝切除术使粒细胞数量和比例增加。
NKT细胞和粒细胞均参与了部分肝切除术后的肝脏炎症。发现NKT细胞而非粒细胞的功能对他克莫司的免疫抑制作用敏感。