Basse P, Hokland P, Heron I, Hokland M
J Natl Cancer Inst. 1988 Jul 6;80(9):657-65. doi: 10.1093/jnci/80.9.657.
The arrest, retention, and elimination (i.e., clearance) of radiolabeled YAC-1 lymphoma cells injected either iv or into the left ventricle (LV) of the heart were studied in male BALB/c mice, with special emphasis on the role of natural killer (NK) cells. After iv injection YAC-1 cells were arrested and, to a large extent, destroyed in the lungs, which contain the first capillary bed that iv injected tumor cells meet. After LV injection the initial distribution of the tumor cells, which depends on the distribution of cardiac output at the time of injection, was estimated by use of radiolabeled microspheres. Using this technique, we have shown that LV-injected tumor cells, in contrast to iv injected tumor cells, were not arrested in the first capillary bed that they encountered but passed viably through the microvasculature of the brain, heart, kidneys, intestinal tract, and to some extent, the bone, skin, and muscle. The only organs that could arrest the LV-injected tumor cells were the lungs and the liver. In the lungs clearance of YAC-1 cells began immediately after the cells were arrested. However, the rate of clearance could be almost abrogated by pretreatment of the recipients with anti-asialo GM1 antiserum, which destroys most of the NK cells in vivo and strongly depresses the in vitro NK cell activity. In contrast, YAC-1 cells arrested in the liver were not cleared from this organ during the first 1-2 hours after arrest. After this delay clearance of the cells commenced. Pretreatment of the recipients with anti-asialo GM1 also strongly depressed the clearance of tumor cells from the liver. Although pretreatment with polyinosinic-polycytidylic acid enhanced in vitro NK cell activity, it could augment only slightly the clearance of YAC-1 cells from the lungs and the liver. Thus these results strongly support the hypothesis that the rapid clearance of tumor cells from both the lungs and the liver depends, at least partially, on the NK cell activity within these organs.
在雄性BALB/c小鼠中研究了静脉注射或注射到心脏左心室（LV）的放射性标记YAC-1淋巴瘤细胞的捕获、滞留和清除（即清除率），特别强调了自然杀伤（NK）细胞的作用。静脉注射后，YAC-1细胞在肺中被捕获，并在很大程度上被破坏，肺中含有静脉注射的肿瘤细胞遇到的第一个毛细血管床。左心室注射后，利用放射性标记微球估计肿瘤细胞的初始分布，其取决于注射时的心输出量分布。使用该技术，我们已经表明，与静脉注射的肿瘤细胞相比，左心室注射的肿瘤细胞不会在它们遇到的第一个毛细血管床中被捕获，而是能够存活地穿过脑、心脏、肾脏、肠道的微血管，并且在一定程度上穿过骨骼、皮肤和肌肉。唯一能够捕获左心室注射的肿瘤细胞的器官是肺和肝脏。在肺中，YAC-1细胞被捕后立即开始清除。然而，用抗去唾液酸GM1抗血清预处理受体可几乎消除清除率，该抗血清在体内破坏大部分NK细胞并强烈抑制体外NK细胞活性。相比之下，在肝脏中被捕的YAC-1细胞在被捕后的最初1-2小时内不会从该器官中清除。在此延迟后，细胞开始清除。用抗去唾液酸GM1预处理受体也强烈抑制肿瘤细胞从肝脏中的清除。虽然用聚肌苷酸-聚胞苷酸预处理可增强体外NK细胞活性，但它只能略微增加YAC-1细胞从肺和肝脏中的清除率。因此，这些结果有力地支持了这样的假设，即肿瘤细胞从肺和肝脏中的快速清除至少部分取决于这些器官内的NK细胞活性。
