TIAZOFURIN INDUCES A DOWN-MODULATION OF ICAM-1 EXPRESSION ON K562 TARGET-CELLS IMPAIRING NK ADHESION AND KILLING

Tiazofurin treatment of K562 leukemia cells in vitro depletes the meta bolites of the guanylate biosynthetic pathway, inducing erythroid diff erentiation, that, in turn, alters the phenotypic profile. As a conseq uence, K562 cells possibly modify their interaction with immune cells. Here we describe the binding and killing activity of peripheral blood NR cells against differentiating K562 cells and the correlation betwe en their altered binding capacity and ICAM-1 expression levels in diff erentiating K562 cells. We found that decreased percentages of NK (and T) cells were bound to differentiating K562 cells generating a decrea sed cytotoxic activity. This corresponded to decreased expression of I CAM-1, as detected by FAGS analysis and Western blot. Erythroid differ entiation, binding and killing reduction, and ICAM-1 down-modulation w ere completely abrogated by guanosine treatment. Tiazofurin causes a d ecrease in lymphocyte recognition and binding to K562 target cells. Th is can be ascribed to the down-modulation of ICAM-1 expression on targ et cells, which, therefore, can escape killing, acquiring a selective survival advantage. (C) 1995 Academic Press, Inc.