Heuff G, Oldenburg H S, Boutkan H, Visser J J, Beelen R H, Van Rooijen N, Dijkstra C D, Meyer S
Department of Surgery, Free University Hospital, Amsterdam, The Netherlands.
Cancer Immunol Immunother. 1993 Jul;37(2):125-30. doi: 10.1007/BF01517045.
The evidence that Kupffer cells are capable of controlling metastatic growth in the liver in vivo is largely circumstantial. The best approach when studying natural cytotoxicity activities of Kupffer cells is to investigate the effect of Kupffer cell elimination on tumour growth. Until now it has not been possible to eliminate Kupffer cells without affecting other cell populations. We have recently developed a new method to eliminate Kupffer cells selectively: intravenous injection of liposome-encapsulated (dichloromethylene)bisphosphonate (Cl2MDP-liposomes) leads to effective elimination of all Kupffer cells, without affecting non-phagocytic cells. Wag/Rij rats were injected with Cl2MDP-liposomes. After 48 h, rats were inoculated with syngeneic CC531 colon carcinoma cells by injection in the portal system. The results show a strongly enhanced tumour growth in the liver of the Cl2MDP-liposome-treated rats. In these animals, livers were almost completely replaced by tumour and had increased in weight, whereas in the control groups only a few (four to eight) small (1-mm) tumour nodules were found. These data show that selective elimination of Kupffer cells results in enhanced tumour growth in the liver, implying that Kupffer cells play a crucial role in controlling tumour growth in the liver.
库普弗细胞能够在体内控制肝脏中转移瘤生长的证据大多是间接的。研究库普弗细胞自然细胞毒性活性的最佳方法是研究消除库普弗细胞对肿瘤生长的影响。到目前为止，还无法在不影响其他细胞群体的情况下消除库普弗细胞。我们最近开发了一种选择性消除库普弗细胞的新方法：静脉注射脂质体包裹的（二氯亚甲基）双膦酸盐（Cl2MDP-脂质体）可有效消除所有库普弗细胞，而不影响非吞噬细胞。给Wag/Rij大鼠注射Cl2MDP-脂质体。48小时后，通过门静脉系统注射给大鼠接种同基因CC531结肠癌细胞。结果显示，经Cl2MDP-脂质体处理的大鼠肝脏中肿瘤生长明显增强。在这些动物中，肝脏几乎完全被肿瘤取代且重量增加，而在对照组中仅发现少数（4至8个）小的（1毫米）肿瘤结节。这些数据表明，选择性消除库普弗细胞会导致肝脏中肿瘤生长增强，这意味着库普弗细胞在控制肝脏肿瘤生长中起关键作用。
