DEFECTIVE CALCIUM INFLUX IN RAT MYELOMONOCYTIC LEUKEMIA-CELLS WHICH ARE RESISTANT TO DIFFERENTIATION-INDUCING EFFECTS OF LIPID-A

We compared the calcium mobilization in parent lipid A-sensitive leuke mia cells (P2) and lipid A-resistant cells (LR) after treating them wi th lipid A in order to clarify the signal transduction involved in the differentiation induced by lipid A. Lipid A induced differentiation i n P2 cells; however, LR cells were completely resistant to it. A drama tic elevation of intracellular free calcium ion concentration ([Ca2+]( i)) occurred in P2 cells, but only a slight elevation of [Ca2+](i) in LR cells. Calcium ionophore in combination with lipid A induced differ entiation in LR cells. An elevation of [Ca2+](i) observed in P2 cells was abrogated by an addition of EGTA, which partially inhibited the di fferentiation of P2 cells stimulated by lipid A. Altogether, these dat a indicate that calcium influx is essential for the differentiation of P2 cells stimulated by lipid A and that defective calcium influx is r esponsible for the resistance to lipid A in LR cells. (C) 1996 Academi c Press, Inc.