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

Journal Article · Sat Apr 01 00:00:00 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), Vol. 86:8; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

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