Plasma lipoproteins and monocyte-macrophages in a peroxisome-deficient system: study of a patient with infantile refsum disease.
Hypocholesterolaemia in infantile Refsum disease (IRD) may link peroxisomes and lipoprotein metabolism. In our patient, plasma cholesterol levels were reduced to 26% and 29% of control in LDL and HDL fractions, respectively. Plasma apolipoproteins B-100 and A-I levels were 52% and 66% of controls, respectively. In the kindred, plasma cholesterol concentration was 61-73% of controls. The HDL-cholesterol/apo A-I ratios were: patient 0.12; kindred 0.17; controls 0.28. Analysis of the IRD patient's lipoprotein revealed compositional abnormalities in all fractions. The patient's LDL demonstrated a substantial reduction in its lipid-to-protein ratio. Alterations in plasma lipoproteins affect their interaction with macrophages. Upon incubation of the patient's LDL with J-774 macrophages, its cellular uptake, measured as cholesterol esterification rate, was only 66% of a control rate. The abnormal LDL of the IRD patient showed also only 25% of control susceptibility to in vitro oxidation. Studies of cellular cholesterol metabolism in the patient's monocyte-derived macrophages (MDM) showed 57% increased cholesterol esterification rate in comparison to normal MDM. The possible link between lipoprotein abnormalities and monocyte-macrophage cholesterol metabolism is discussed.
D000818:Animals; D001053:Apolipoproteins / Q000097:blood; D002460:Cell Line; D002648:Child; D002784:Cholesterol / Q000097:blood; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007958:Leukocyte Count; D008074:Lipoproteins / Q000097:blood*; D008264:Macrophages; D008297:Male; D051379:Mice; D008830:Microbodies / Q000502:physiology*; D009000:Monocytes; D010084:Oxidation-Reduction; D012035:Refsum Disease / Q000097:blood* / Q000235:genetics; D014280:Triglycerides / Q000097:blood
D001053:Apolipoproteins; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol