Effect of plasma lipoproteins on cholesterol accumulation in macrophages: comparison of lipoproteins from normal and homozygous familial hypercholesterolemic subjects.

Total cholesterol (TC) content of mouse peritoneal macrophages (MPM) increased when incubated with increasing concentrations of normal low density (N-LDL) or very low density (N-VLDL) lipoprotein. Incubation with increasing concentrations of normal high density lipoprotein (N-HDL) caused a decrement in cellular mass of TC in MPM. Incubation of MPM with serum from normal subjects as well as from subjects with homozygous familial hypercholesterolemia (HFH) resulted in a 25% increment in cellular mass of TC, due to an increment in both free cholesterol (FC) and cholesteryl ester (CE) fractions. Accumulation of TC in MPM, due mainly to elevation of CE, was observed when the macrophages were incubated in the presence of LDL or VLDL derived from either group of subjects. N-LDL caused a higher increment in cellular CE compared to HFH-LDL. However, the presence of HFH-VLDL in the medium caused elevation in the cellular TC and CE content to a higher level than did N-VLDL. The presence of N-HDL as well as of HFH-HDL in the medium resulted in a similar decrement in the cholesterol content of MPM. The decrement was expressed in both FC and CE fractions. The present study shows different abilities of normal and HFH plasma lipoproteins to cause cholesterol accumulation in MPM.