Cholesterol synthesis in cultured human peripheral lymphocytes. Influence of LDL, HDL, cholesterol/phosphatidylcholine liposomes and complete serum.

Lipoprotein-deficient milieu, freshly isolated human peripheral blood lymphocytes lose about 50% of their membrane cholesterol into the medium within 8 h. The cholesterol loss is counter-regulated by de novo synthesis commencing after a lag phase of 8-12 h, and reaching a steady state within 24 h at a diminished membrane cholesterol level. About 50 micrograms free cholesterol/ml, offered in the form of low-density lipoproteins (LDL) and cholesterol/phosphatidylcholine liposomes, suppressed cholesterol synthesis to about 20% of that controls (lipoprotein-deficient culture). By contrast, pure phosphatidylcholine liposomes enhanced cholesterol synthesis to about 150% of control values. High-density lipoproteins (HDL) exerted a slightly suppressive effect on cholesterol synthesis only at high concentrations (greater than 100 micrograms HDL cholesterol/ml). HDL added to cultures containing fixed concentrations of LDL led to a dose-dependent neutralization of LDL suppression of cholesterol synthesis. Culture medium containing complete serum caused a suppression of cholesterol synthesis to about 50% of the control. The lesser reduction in cholesterol synthesis caused by complete serum compared with LDL or cholesterol/phosphatidylcholine liposomes can be explained by the presence of HDL in the former. Our results support the view that the cholesterol requirement of blood lymphocytes in their lipid-rich milieu is met by cholesterol neosynthesis as well as an exchange mechanism with surrounding lipoproteins. In our system, the cholesterol neosynthesis appears to be controlled by the ratio of LDL to HDL in the surrounding medium.