Apoprotein E mediates the interaction of beta-VLDL with macrophages.
beta-Very low density lipoproteins (beta-VLDL) isolated from cholesterol-fed rhesus monkeys stimulated cholesteryl ester synthesis and accumulation in mouse peritoneal macrophages. The apoprotein specificity and requirement for the cell surface uptake of beta-VLDL was investigated by treating the beta-VLDL with trypsin (beta-VLDL (T], incubating the beta-VLDL (T) with other lipoproteins or apoproteins, reisolating the beta-VLDL (T) and measuring its biological activity which, for this study, is defined as the ability of the lipoprotein to stimulate cholesterol esterification in the macrophages. Trypsin treatment of beta-VLDL abolished its biological activity. Apoprotein analysis of the beta-VLDL (T) demonstrated the absence of intact apoproteins B-100, B-48, and E. The J774 macrophage-like cell line and mouse peritoneal macrophages responded similarly with respect to cholesterol esterification following incubation with inactive and treated beta-VLDL. The J774 macrophage-like cell line was used to establish the conditions necessary for the restoration of biologic activity to the trypsinized beta-VLDL. The loss of biological activity of beta-VLDL (T) could be reversed by restoring apoprotein E-containing LDL from hyperlipemic monkeys or purified apoprotein E. Apoprotein A-I had no such effect. The restored biological activity of the beta-VLDL (T) was proportional to the amount of apoprotein E acquired by the lipoprotein. beta-VLDL particles composed of apoprotein E and either intact or degraded apoprotein B-100 had comparable biological activity. Thus, intact apoprotein E, without intact apoprotein B, is a sufficient mediator for the biological activity and metabolism of beta-VLDL by macrophages and plays a major role in receptor-lipoprotein interaction.
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D002849:Chromatography, Gas; D046508:Culture Techniques; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006868:Hydrolysis; D008079:Lipoproteins, VLDL / Q000097:blood*; D008253:Macaca mulatta; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010529:Peritoneal Cavity / Q000166:cytology; D014357:Trypsin
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008079:Lipoproteins, VLDL; D002784:Cholesterol; D014357:Trypsin