MODULATION OF TISSUE PLASMINOGEN-ACTIVATOR BIOSYNTHESIS BY PHOSPHATIDYLINOSITOL LIPOSOMES IN HUMAN FETAL LUNG FIBROBLASTS

Phosphatidylinositol (Pl) liposomes at 40-mu-M increased tissue plasminogen activator (t-PA) biosynthesis by human fetal lung fibroblasts IMR-90 (FLF), after 5 days of incubation by 7.4 +/- 1.4 times of the control level. Other phospholipid liposomes, such as phosphatidylserine (PS), phosphatidylcholine (PC), and phosphatidylglycerol (PG), had no effect on t-PA biosynthesis by FLF. The induction of t-PA biosynthesis by Pl liposomes was inhibited by specific inhibitors of phosphoinositide pathway: gentamycin and lithium chloride. Thus, gentamycin inhibited the effect of Pl liposomes on t-PA biosynthesis by 76% (P < 0.001), while it had no effect on control FLF. Likewise, lithium chloride inhibited t-PA biosynthesis of both Pl-treated and control FLF by > 84%. The induction of t-PA biosynthesis by Pl liposomes was dependent on RNA transcription and independent of DNA biosynthesis.