Phagocytosis of aggregated lipoprotein by macrophages: low density lipoprotein receptor-dependent foam-cell formation.
Low density lipoprotein (LDL) modified by incubation with phospholipase C (PLC-LDL) aggregates in solution and is rapidly taken up and degraded by human and mouse macrophages, producing foam cells in vitro. Human, mouse, and rabbit macrophages degraded 125I-labeled PLC-LDL (125I-PLC-LDL) more rapidly than native 125I-labeled LDL (125I-LDL), while nonphagocytic cells such as human fibroblasts and bovine aortic endothelial cells degraded 125I-PLC-LDL more slowly than 125I-LDL. This suggested the mechanism for internalization of PLC-LDL was phagocytosis. When examined by electron microscopy, mouse peritoneal macrophages appeared to be phagocytosing PLC-LDL. The uptake and degradation of 125I-PLC-LDL by human macrophages was inhibited greater than 80% by the monoclonal antibody C7 (IgG2b) produced by hybridoma C7, which blocks the ligand binding domain of the LDL receptor. Similarly, methylation of 125I-LDL (125I-MeLDL) prior to treatment with phospholipase C decreased its subsequent uptake and degradation by human macrophages by greater than 90%. The uptake and degradation of phospholipase C-modified 125I-MeLDL by macrophages could be restored by incubation of the methylated lipoprotein with apoprotein E, a ligand recognized by the LDL receptor. These results indicate that macrophages internalize PLC-LDL by LDL receptor-dependent phagocytosis.
Suits
A G
AG
Department of Medicine, University of Washington, Seattle 98195.
Chait
A
A
Aviram
M
M
Heinecke
J W
JW
D000818:Animals; D000937:Antigen-Antibody Reactions; D001057:Apolipoproteins E / Q000378:metabolism; D005487:Foam Cells / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D008854:Microscopy, Electron; D010587:Phagocytosis; D011973:Receptors, LDL / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism
D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D010738:Type C Phospholipases