ENHANCED HUMAN KUPFFER CELL-MEDIATED CYTOTOXICITY AFTER ACTIVATION OFTHE EFFECTOR-CELLS AND MODULATION OF THE TARGET-CELLS BY INTERFERON-GAMMA - A MECHANISTIC STUDY AT THE CELLULAR-LEVEL

In this study we demonstrate enhanced Kupffer cell (KC) cytotoxicity a gainst several colorectal cell lines by activation of KC and by modula tion of the targets (SW948, WiDR, HT29, and SW620) with IFN-gamma. We demonstrated that soluble TNF-alpha had no effect on these tumor cells , while cytotoxicity against SW948 and WiDR was blocked by anti-TNF-al pha. Experiments using a transwell system stressed the importance of c lose intercellular contact for this process. Anti-IL-l did not inhibit cytotoxicity against SW948. Modulation of HT29, WiDR, and SW948 by IF N-gamma (500 U/ml) induced a significant increase in cytotoxicity. We conclude that cell-associated TNF-LU may be responsible for KC cytotox icity against SW948, a process requiring close intercellular contact. WiDR is only partly lysed by a TNF-alpha-dependent mechanism, whereas HT29 is not. Furthermore, IFN-gamma is involved in the regulation of t umor susceptibility. (C) 1995 Academic Press, Inc.