NK cell sensitivity of the leukemic K 562 cells; effect of sodium butyrate and hemin induction.

Abstract

Two differentiation inducers, hemin and sodium butyrate, have been studied for their effect on the NK sensitivity of human leukemic K 562 cells. When cultivated in the presence of 0.1 mM hemin, K 562 cells increased their hemoglobin synthesis. However, their susceptibility to NK lysis remained unaffected. On the other hand, sodium butyrate, which is known as a more potent differentiating agent, consistently reduced the NK sensitivity of K 562 cells and simultaneously induced the appearance of several differentiation markers. The effect of sodium butyrate on NK sensitivity was dose-dependent (maximal action at 2-mM concentration), appeared after 2 days in culture, and was maximal after 5 days. After sodium butyrate removal from the culture medium, K 562 cells recovered their normal NK susceptibility within 4 days. In cold-target competition experiments, untreated K 562 cells acted as better competitors than butyrate-treated K 562 cells. Target-binding cell assays and specific NK cell removal on K 562 monolayers demonstrated that NK cells were less adherent to butyrate-treated than to control K 562 cells. From these data, it could be postulated that sodium butyrate modulates the expression of some target structure(s) involved in NK target binding. Five subclones of K 562 have been selected for exhibiting distinct, stable properties with regard to their cellular commitment (either to erythroid or to megakaryocytic lineage). The NK sensitivity of these subclones was roughly identical, and in all of them, butyrate treatment induced similar protection against NK-mediated lysis. Thus, the susceptibility to NK lysis and its modulation did not depend upon the predominant lineage present in each clone.