Changes in the Susceptibility of 12-O-Tetradecanoyl-phorbol 13-Acetate (TPA)-Treated HL-60 Cells to Staphylococcal Leukocidin

Abstract

Susceptibility of human promyelocytic leukemia HL-60 cells to staphylococcal leukocidin following treatment of cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) was examined. TPA treatment for 6 hr rendered the cells very resistant transiently to leukocidin. There was no change in binding of leukocidin to the cells, but leukocidin-induced45CaCl2 influx, phospholipase A2 and C activities were inhibited. Further incubation with TPA rendered the cells sensitive again and then more sensitive than original HL-60 cells following increase of the binding, and leukocidin-induced activities described above appeared again. Those cells treated with TPA for more than 18 hr started to differentiate to macrophages morphologically and functionally. These data suggest that the differentiated cells were more sensitive than original HL-60 cells because of increased binding of leukocidin and that treatment of TPA for 6 hr may transiently impair the signal transduction system of leukocidin after binding of leukocidin to the specific receptor of the cell membrane. Using these TPA-treated cells, it was shown in this report that calcium influx, phospholipase A2 and C activities were important to induce cytotoxic action of leukocidin after binding of leukocidin to specific receptors on the cells. © 1993, Center For Academic Publications Japan. All rights reserved.