NATURAL-KILLER CELL-ACTIVITY - AGE, ESTROUS-STAGE AND CIRCADIAN-STAGE DEPENDENCE AND INVERSE CORRELATION WITH METASTATIC POTENTIAL
NATURAL-KILLER CELL-ACTIVITY - AGE, ESTROUS-STAGE AND CIRCADIAN-STAGE DEPENDENCE AND INVERSE CORRELATION WITH METASTATIC POTENTIAL
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DOI：
10.1093/jnci/80.15.1232
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发表时间：
1988-10-05
影响因子：
10.3
通讯作者：
SIMMONS, RL
中科院分区：
文献类型：
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作者：
HRUSHESKY, WJM;GRUBER, SA;SIMMONS, RL
动情周期内手术切除移植的小鼠乳腺肿瘤的时间深刻影响肺转移的频率。我们通过测量两个年龄组的同基因无肿瘤小鼠在每个昼夜节律时间和四个发情阶段的脾脏自然杀伤 (NK) 细胞活性和白细胞介素 2 (IL-2) 的产生来研究免疫反应在这种现象中的潜在作用。通过在处死和收获脾脏之前立即评估阴道涂片细胞结构来确定动情阶段。在单细胞脾细胞制剂中，使用放射性标记的铬释放测定评估针对标准肿瘤细胞靶标的 NK 细胞毒性，同时利用 IL-2 依赖性 CTLL-2 细胞系在生物测定中测定 IL-2 活性。研究发现，年轻组小鼠的 NK 活性高出 8 倍，IL-2 产量高出 35%。将 NK 和 IL-2 值与年龄标准化后，在四个动情期和两个昼夜节律阶段之间发现 NK 活性存在高度统计学显着差异。在每个动情阶段的每日休息期间，NK 活性都较高。在光照范围内采样时，IL-2 值在发情间期和发情前期最高；在黑暗中采样时，在发情后期中 IL-2 值最高。生育周期中与最低转移潜力（发情前期/发情期）相关的阶段与脾细胞 NK 活性最高的阶段精确对应。这些结果表明，细胞免疫反应的一个重要组成部分在宿主的生育周期和昼夜节律周期中都有节奏地变化。 NK 活性的节律性变化可能在一定程度上导致了术后转移性播散的类似节律性频率。
The timing within the estrous cycle of surgical removal of a transplanted murine mammary tumor profoundly influences the frequency of pulmonary metastases. We investigated the potential role of the immune response in this phenomenon by measuring splenic natural killer (NK) cell activity and interleukin-2 (IL-2) production in syngeneic tumor-free mice of two age groups at each of two circadian times and in each of four estrous stages. Estrous stage was determined by assessment of vaginal smear cellularity immediately prior to killing and spleen harvest. In a single-cell splenocyte preparation, NK cytotoxicity against a standard tumor cell target was assessed using a radiolabeled chromium release assay while IL-2 activity was determined in a bioassay utilizing the IL-2-dependent CTLL-2 cell line. Mice from the younger group were found to have eight-fold higher NK activity and 35% greater IL-2 production. After normalization of NK and IL-2 values for age, a highly statistically significant difference in NK activity was found among the four estrous and between the two circadian stages of sacrifice. NK activity was greater during the daily resting span across every estrous stage. IL-2 values were highest in diestrus and proestrus when sampled in the light span and in estrus-metestrus when sampled in the dark. The stages within the fertility cycle associated with lowest metastatic potential (proestrus/estrus) correspond precisely with those of highest splenocyte NK activity. These results indicate that an important component of the cellular immune response varies rhythmically both during the fertility and circadian cycles of the host. The rhythmic changes in NK activity may be in part responsible for the similarly rhythmic frequency of postsurgical metastatic dissemination.