The role of Kupffer cells in the surveillance of tumor growth in the liver.

The present study was designed to investigate the role of Kupffer cells (Kc) in the surveillance of liver tumors. We examined the antitumor activity of Kc by 51Cr releasing assay and inhibition of [3H]thymidine ([3H]TdR) incorporation into tumor cells. We also studied the change in the growth of liver tumors following the activation and the blockade of Kc. The cytotoxicity of Kc against K562 increased as the effector:target (E:T) ratio rose and reached its maximum level of about 18% at an E:T ratio of 20:1. [3H]TdR incorporation into target cells (P815 and AH130) was also inhibited by Kc. Such antitumor activity of Kc was augmented by OK432 (K562, from 13.8 +/- 5.6 to 21.9 +/- 2.5%; AH130, from 19.2 +/- 14.5 to 37.1 +/- 12.6%). In the experiment of the inoculation of AH130 via the portal vein, OK432 decreased the number of hepatic foci, whereas macrophage inhibitors carrageenan and gadolinium increased the number of tumor nodules. In addition, gadolinium injection reduced the number of Kupffer cells reactive with monoclonal antibodies directed against macrophages ED2 and Ki-M2R. Tumor growth in the liver was maximum in rats with both gadolinium treatment and splenectomy. In conclusion, Kc have antitumor activity, and augmentation of Kc may be a possible strategy to prevent hematogenous hepatic metastasis.