Erythrocyte-bound low-density lipoprotein immune complexes lead to cholesteryl ester accumulation in human monocyte-derived macrophages.
We have recently shown that incubation of macrophages with insoluble immune complexes (IC) containing low-density lipoproteins (LDL) leads to intracellular accumulation of esterified cholesterol (CE). This accumulation is associated with morphological transformation of the macrophages into "foam cells." In order to better characterize the conditions that lead to the uptake of LDL-IC and CE accumulation on macrophages, we studied the effects of soluble, insoluble, and red blood cell (RBC)-bound LDL-IC on macrophage lipid and lipoprotein metabolism. Using both apoB or IgG [anti-LDL] as the labeled moieties, we observed that the uptake of LDL-IC by human monocyte-derived macrophages (HMM) was markedly enhanced when the IC were adsorbed to RBC. Competition studies with unlabeled heat-aggregated IgG, native LDL, and acetylated LDL demonstrated that LDL-IC were ingested via the Fc receptor of HMM. The uptake of RBC-bound LDL-IC led to a marked intracellular accumulation of cholesteryl esters in HMM (78.4 +/- 1.7 vs 5.5 +/- 0.6 micrograms/mg cell protein; P less than 0.01) which apparently resulted from delayed degradation of the ingested LDL. Thus, it appears that the metabolism of LDL is altered when it is ingested as part of an antigen-antibody complex. These findings suggest that the formation of LDL-IC and their adsorption to red cells may play a significant role in the onset or in the evolution of human atherosclerosis.
Gisinger
C
C
Veterans Administration Medical Center, Charleston, South Carolina.
Virella
G T
GT
Lopes-Virella
M F
MF
D000936:Antigen-Antibody Complex; D001667:Binding, Competitive; D002788:Cholesterol Esters / Q000096:biosynthesis*; D004306:Dose-Response Relationship, Immunologic; D004912:Erythrocytes; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D011961:Receptors, Fc / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D000936:Antigen-Antibody Complex; D002788:Cholesterol Esters; D007074:Immunoglobulin G; D008077:Lipoproteins, LDL; D011961:Receptors, Fc