Phagocytosis of aggregated lipoprotein by macrophages: Low density lipoprotein receptor-dependent foam-cell formation

Journal Article · Fri Mar 31 23:00:00 EST 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.8.2713· OSTI ID:5443211

Suits, A G; Chait, A; Aviram, M; Heinecke, J W ^[1]

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1. Univ. of Washington, Seattle (USA)

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 {sup 125}I-labeled PLC-LDL ({sup 125}I-PLC-LDL) more rapidly than native {sup 125}I-labeled LDL ({sup 125}I-LDL), while nonphagocytic cells such as human fibroblasts and bovine aortic endothelial cells degraded {sup 125}I-PLC-LDL more slowly than {sup 125}I-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 {sup 125}I-PLC-LDL by human macrophages was inhibited >80% by the monoclonal antibody C7 (IgG2b) produced by hybridoma C7, which blocks the ligand binding domain of the LDL receptor. Similarly, methylation of {sup 125}I-LDL ({sup 125}I-MeLDL) prior to treatment with phospholipase C decreased its subsequent uptake and degradation by human macrophages by >90%. The uptake and degradation of phospholipase C-modified {sup 125}I-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.

• OSTI ID: 5443211
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 86:8; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BIODEGRADATION
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
DISEASES
DOSE-RESPONSE RELATIONSHIPS
ELECTRON CAPTURE RADIOISOTOPES
ELECTRON MICROSCOPY
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
LIPIDS
LIPOPROTEINS
MACROPHAGES
MAMMALS
MAN
MEMBRANE PROTEINS
MICE
MICROSCOPY
MONOCARBOXYLIC ACIDS
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
OLEIC ACID
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHAGOCYTES
PHAGOCYTOSIS
PRIMATES
PROTEINS
RABBITS
RADIOISOTOPES
RECEPTORS
RODENTS
SOMATIC CELLS
TRANSMISSION ELECTRON MICROSCOPY
UPTAKE
VERTEBRATES