Evidence of direct interaction between Kupffer cells and colon cancer cells: an ultrastructural study of the co‐culture

A co-culture study of purified rat Kupffer cells and human colon cancer cells was performed, and the process of the tumor cell injury was observed under an inverted type fluorescence microscope loaded with propidium iodide, and also under an electron microscope. Ultrastructurally there was direct membrane-to-membrane interaction between Kupffer cells and colon cancer cells in time. The interaction occurred 1 h after start of the co-culture, and injured tumor cells were observed closely attached to pseudopodia of Kupffer cells at 6 h. The number of propidium iodide-positive tumor cells with damage increased in time. Pretreatment with NG-monomethyl-L-arginine reduced the number of injured tumor cells without preventing morphological interactions, but superoxide dismutase did not prevent the tumoricidal effect. Pretreatment with trypsin completely inhibited cell interaction and damage to tumor cells. In conclusion, the morphological interaction of Kupffer cells as a first step and the involvement of nitric oxide-derived free radicals as a second step seem to play a significant role in the host-defense mechanism.