Regulation of prostaglandin synthesis during differentiation of cultured mouse myeloid leukemia cells

✍ Scribed by Yoshio Honma; Takashi Kasukabe; Motoo Hozumi; Yasuko Koshihara

• Publisher: John Wiley and Sons
• Year: 1980
• Tongue: English
• Weight: 674 KB
• Volume: 104
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041040308

✦ Synopsis

Mouse myeloid leukemia cells (MI) were induced to differentiate into mature macrophages and granulocytes by various inducers. The differentiated M1 cells synthesized and released prostaglandins, whereas untreated M1 cells did not. When the cells were prelabelled with [ 14C]arachidonate, the major prostaglandins released into the culture media were found to be prostaglandin E,, D,, and F,, in an early stage of differentiation, but the mature cells produced predominantly prostaglandin E,. The synthesis and release of prostaglandins were completely inhibited by indomethacin. Dexamethasone, a potent inducer of differentiation of MI cells, did not induce production of prostaglandins in resistant M1 cells that could not differentiate even with a high concentration of dexamethasone. These results suggest that production of prostaglandins in M1 cells is closely associated with differentiation of the cells. Homogenates of dexamethasonetreated M1 cells converted arachidonate to prostaglandins, but this conversion was scarcely observed with homogenates of untreated M1 cells. Dexamethasone and the other inducers stimulated the release of arachidonate from phospholipids. Therefore, induction of prostaglandin synthesis during differentiation of M1 cells may result from induction of prostaglandin synthetase activity and stimulation of the release of arachidonate from cellular lipids. Lysozyme activity, which is a typical biochemical marker ofmacrophages, was induced in MI cells by prostaglandin E, or D, alone, as well as by inducers of differentiation of the cells, but it was not induced by arachidonate or prostaglandin F, These results suggest that prostaglandin synthesis is important in differentiation of myeloid leukemia cells.