DIFFERENTIATION OF U937 MYELOMONOCYTIC CELL-LINE BY ALL-TRANS-RETINOIC ACID AND 1,25-DIHYDROXYVITAMIN D-3 - SYNERGISTIC EFFECTS ON TISSUE TRANSGLUTAMINASE

We studied tissue transglutaminase (TGase) expression in human myelomo nocytic leukemia cells treated by combinations of all-trans retinoic a cid (RA) and 1,25 dihydroxyvitamin D-3 (VD). We found that in U937 cel ls, as in HL-60 and THP-1 cells, RA alone caused an early induction of enzyme activity, correlated with increased mRNA expression. VD alone also induced rapid TGase mRNA expression but in this case TGase enzyma tic activity was not measurable until 96 h following onset of treatmen t. Combinations of both agents had no additional effects over those of RA alone on HL-60 cells, THP-1, and U937 cells during the first 48 h. However, following further incubation, U937 cells expressed increased levels of TGase when treated by both agents. By many criteria, includ ing their sensitivity to various inducers of oxidative burst, lipopoly saccharide-induced production of monokines and in the present work, ly sozyme secretion and TGase expression, U937 cells exposed to combinati ons of RA and VD exhibit a behavior different from those of HL-60 and THP-1 cells. They represent a type of leukemia cell amenable by this t reatment to a stage close to that of a terminally differentiated macro phage.