Cholesterol and phospholipid biosynthesis in guinea pig megakaryocytes

Megakaryocytes are the bone marrow cells which produce the blood platelets. Platelet lipids are thought to be important determinants of platelet activity in thrombosis and hemostasis. We have investigated lipid synthesis from [U-14C]-acetate in isolated guinea pig megakaryocytes with the goal of elucidating the genesis of platelet lipids. Cholesterol was the major product of megakaryocyte lipid synthesis from [U-14C]acetate. Incorporation of acetate (0.1 mM) into cholesterol per 10(6) megakaryocytes (1.1 mg protein) was 0.14 nmol in 0.5 h, 0.95 nmol in 1.5 h and 3.2 nmol in 4.0 h. Megakaryocytes also synthesized cholesterol from [U-14C]glucose. In contrast, platelet sterol synthesis was negligible. Both megakaryocytes and platelets synthesized phospholipids from [U-14C]acetate. Megakaryocytes incorporated 0.07 nmol acetate per 10(6) cells into phospholipid in 0.5 h, 0.38 nmol in 1.5 h and 1.8 nmol in 4.0 h. Platelets (10(9) cells, 1.3 mg protein) incorporated 0.15 nmol acetate into phospholipids in 1.5 h. Phosphatidylcholine accounted for 62% of the phospholipid radioactive label in megakaryocytes and 78% in platelets. Phospholipid radioactivity was associated with the fatty acids. We hypothesize that the megakaryocyte may synthesize a major portion of platelet cholesterol and that the phospholipid and fatty acid synthetic pathways available to the platelet are derived from the megakaryocytes.