Itoh H, Abo T, Sugawara S, Kanno A, Kumagai K
Department of Microbiology, Tohoku University School of Dentistry, Sendai, Japan.
J Immunol. 1988 Jul 1;141(1):315-23.
We investigated the distribution of liver NK cells in mice of various ages and their cytotoxicity against regenerating hepatocytes. Liver NK cells were identified by asialo GM1 antibody in mononuclear cell suspension from the liver, whereas NK activity was assayed against YAC-1 target cells. Mononuclear cells in the liver consisted of more than 25% NK cells with potent NK activity in C3H/He mice, 8 wk of age. The strain-specific distribution (C3H/He greater than C57BL/6 greater than DBA/2) of liver NK cells was the same as those in the spleen and blood. The proportion of liver NK cells and the level of NK activity in C3H/He mice were further demonstrated to vary depending on age, in that both the proportion and the function were generated at 4 wk of age, reached a maximum between the 6th and 8th wk, and then rapidly decreased around the 9th wk. The appearance of an increased number of NK cells in the liver seemed to coincide with the slowing of the rapid increase of murine liver weight. We then investigated whether liver NK cells mediated their cytotoxicity against regenerating hepatocytes. Both specific 51Cr-release assay and single cell cytotoxicity assay demonstrated that liver NK cells were significantly cytotoxic against regenerating hepatocytes in partially hepatectomized liver, but to a lesser extent against normal hepatocytes in resting liver. Morphologic study revealed that normal liver predominantly consisted of hepatocytes with binuclei (greater than 60%) but that regenerating liver mainly consisted of hepatocytes with a single nucleus (greater than 70%). One-nucleus hepatocytes were more susceptible to the cytotoxicity of liver NK cells. A comparative study of restoration kinetics of the liver weight and the number of liver NK cells after partial hepatectomy also showed a unique relationship. These results raise the possibility that liver NK cells might be responsible for regulating hepatocyte growth.
我们研究了不同年龄小鼠肝脏自然杀伤（NK）细胞的分布及其对再生肝细胞的细胞毒性。通过抗唾液酸GM1抗体在肝脏单核细胞悬液中鉴定肝脏NK细胞，而针对YAC-1靶细胞检测NK活性。8周龄的C3H/He小鼠肝脏中的单核细胞由超过25%具有强大NK活性的NK细胞组成。肝脏NK细胞的品系特异性分布（C3H/He＞C57BL/6＞DBA/2）与脾脏和血液中的分布相同。进一步证明，C3H/He小鼠肝脏NK细胞的比例和NK活性水平随年龄而变化，即比例和功能在4周龄时产生，在第6至8周达到最大值，然后在第9周左右迅速下降。肝脏中NK细胞数量增加的出现似乎与小鼠肝脏重量快速增加的减缓相吻合。然后，我们研究了肝脏NK细胞是否介导其对再生肝细胞的细胞毒性。特异性51Cr释放试验和单细胞细胞毒性试验均表明，肝脏NK细胞对部分肝切除肝脏中的再生肝细胞具有显著的细胞毒性，但对静止肝脏中的正常肝细胞的细胞毒性较小。形态学研究表明，正常肝脏主要由双核肝细胞组成（＞60%），而再生肝脏主要由单核肝细胞组成（＞70%）。单核肝细胞更容易受到肝脏NK细胞的细胞毒性作用。部分肝切除术后肝脏重量和肝脏NK细胞数量恢复动力学的比较研究也显示出独特的关系。这些结果增加了肝脏NK细胞可能负责调节肝细胞生长的可能性。
