Low density lipoprotein receptor activity in human monocyte-derived macrophages and its relation to atheromatous lesions.

Abstract

Human peripheral monocytes, isolated from a previously unused source (a leukocyte concentrate byproduct of the plateletphoresis procedure for platelet transfusion), transformed into macrophages while cultured with 5% human serum or isolated lipoprotein fractions. Used for the study of their cholesterol (Chol) metabolism, these human monocyte-derived macrophages had a high-affinity receptor that is saturable, specific for low density lipoprotein (LDL) and maximally induced by incubation for as little as 24 hr in medium devoid of lipoproteins or Chol. Macrophages were shown to have separate receptor activity for 125I-labeled LDL and 125I-labeled acetylated LDL; macrophages that had been incubated with lipoprotein-depleted serum degraded native and acetylated LDL at similar rates. The receptor for LDL was functional in maintaining Chol homeostasis, as demonstrated by feedback inhibition of Chol synthesis after culture with LDL or very low density lipoprotein (VLDL). The Chol content of macrophages was doubled by incubation with medium containing VLDL compared to incubation with LDL (60 microgram of Chol per ml of medium). Incubation with native lipoproteins did not lead to accumulation of esterified Chol by macrophages. Changes in the Chol metabolism of macrophages, rather than modifications in circulating LDL, may cause these cells to store cholesteryl ester and take on the characteristics of cholesteryl ester-laden macrophages of atheromatous lesions.