In earlier studies, we showed that incubation of HMM with LDL IC led to cellular CE accumulation and to the transformation of macrophages into foam cells. This study demonstrates that the stimulation of macrophages with RBC-LDL-IC also increases the uptake of native LDL, most likely because of an increased LDL receptor number, as shown by Scatchard plot analysis (x-axis intercept 1267 vs. 352 ng LDL/mg protein in control cells). To determine whether the increase in LDL-receptor activity was secondary to a decrease in the macrophage free (nonassociated) cholesterol content, we measured the T-UC and the UC associated with intracellular intact LDL and demonstrated that 50% of the T-UC is associated with intact LDL. UC not associated with LDL (free cholesterol) was lower in LDL-IC-stimulated cells than in control cells. These results suggest that UC associated with nondegraded intracellular LDL is nonregulatory, a conclusion that was also supported by finding increased sterol synthesis (192.8 ± 22.9 pmol/mg protein vs. 94.8 ±11.8) in RBC-LDL-IC-stimulated macrophages. In conclusion, the uptake of RBC-LDL-IC by macrophages led to increased intracellular accumulation of CE and UC, to a decrease in the cell regulatory pool of free cholesterol, and to an increase in LDL-receptor activity.

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