Heat treatment of leukemic cell lines can increase their sensitivity to NK lysis.
The effect of stress on target cell susceptibility to human natural killer cell-mediated lysis was examined. Targets were incubated at 37, 42, or 45 degrees C for 1 hr and then tested for NK sensitivity in chromium-release assays. The T cell target JURKAT displayed minor increases in susceptibility to NK lysis with 42 degrees C pretreatment (20-50% increases) and dramatic increases in lysability with 45 degrees C pretreatment (100-300% increase) compared to control. In contrast, lysis of the NK prototypic target K562 is not increased after 42 or 45 degrees C pretreatment. Kinetic studies indicated an optimal NK sensitivity enhancement time of 1 hr at 45 degrees C for JURKAT. Inhibition of target cell protein synthesis by emetine pretreatment does not produce an increase in susceptibility to NK lysis. JURKAT cells pretreated with sodium arsenite exhibited a comparable increase in NK sensitivity to the heat treatments. Cold target inhibition assays suggest that the increase in sensitivity after heat treatment is at a postbinding stage. This was exemplified by the increased sensitivity of JURKAT, but not K562, to lysis mediated by isolated rat NK granules. These results indicate that a heat-sensitive, de novo protein synthesis-independent defense mechanism against lysis may exist in some tumors, altering their susceptibility to lysis by NK cells.
Scott
J E
JE
Duke University Medical Center, Durham, North Carolina 27701, USA.
Dawson
J R
JR
D018053:Arsenites / Q000633:toxicity; D001426:Bacterial Proteins; D003167:Complement Activation / Q000276:immunology; D003594:Cytoplasmic Granules / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006358:Hot Temperature; D006801:Humans; D007114:Immunization; D007694:Killer Cells, Natural / Q000276:immunology*; D013301:Streptolysins / Q000276:immunology; D013312:Stress, Physiological / Q000503:physiopathology*; D014407:Tumor Cells, Cultured / Q000276:immunology
D018053:Arsenites; D001426:Bacterial Proteins; D013301:Streptolysins; C025964:streptolysin O; C015001:arsenite