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Lovastatin is a widely used anticholesterolemic drug which exercises its effect by inhibiting hepatic cholesterol synthesis and up-regulating low density lipoprotein (LDL) receptors. In the present study, we determined that the drug has no adverse effects on the expression of three cell surface antigens of human monocytes, i.e. high affinity Fc receptors (Fc gamma RI), low affinity Fc receptors (Fc gamma RII) and CD14 antigen. We have shown previously these antigens are regulated by cholesterol and lipoproteins. At 0.5 micrograms/mL of culture medium, lovastatin did not reduce the percentage of receptor-positive cells or the average number of receptor molecules per cell. These observations add to the attractiveness of the drug as an anticholesterolemic agent and also indicate that endogenous cholesterol biosynthesis by monocytes is not required for expression of Fc gamma RI, Fc gamma RII, or CD14.

The CD14 antigen which is expressed on human monocytes and macrophages is a phosphatidylinositol-linked surface protein. We investigated the effects of cellular cholesterol depletion and repletion on cell surface expression of this glycoprotein. Adherent normal human monocytes were cultured for four days in media containing delipidated fetal calf serum which depleted cellular cholesterol. Immunofluorescence analysis demonstrated a markedly diminished surface expression of CD14 on cells cultured in delipidated serum compared to normal serum. Expression of CD64 (high-affinity Fc receptors, Fc gamma RI) also was reduced under these conditions. This inhibition of CD14 expression was overcome by addition to the culture medium of cholesterol, low density lipoprotein, or very low density lipoprotein. All of these supplements replenished cellular cholesterol. Expression of CD64(Fc gamma RI) was not restored by addition of cholesterol. These observations indicate that cholesterol can regulate the surface expression of some phosphatidylinositol-anchored glycoproteins.