INVOLVEMENT OF MAC-1-MEDIATED ADHERENCE AND SPHINGOSINE 1-PHOSPHATE IN SURVIVAL OF PHORBOL ESTER-TREATED U937 CELLS

Phorbol esters exert a dual function in human leukemia cells, inductio n of differentiation and activation of integrin-mediated functions. He re we have shown that the plastic adherence of phorbol ester-treated U 937 cells is mediated by expression of integrin Mac-1 (CD11b/CD18) on the cell surface and that these adherent cells exhibit anoikis (apopto sis when adherent cells are detached or adherence is inhibited). We us ed U937-derived clones overexpressing either antisense RNAs antisense to CD11b and CD18 mRNAs or mRNA from a truncated mutant CD11b gene. We have also shown that apoptosis in non-adherent cells or anoikis was m ediated by sphingosine and that survival of adherent cells was achieve d by a shift of the dynamic balance between sphingosine and sphingosin e 1-phosphate toward the latter by adherence-activated sphingosine 1-k inase. (C) 1998 Academic Press.