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

Abstract

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.

Authors:
; ; ;  [1]
  1. Univ. of Washington, Seattle (USA)
Publication Date:
OSTI Identifier:
5443211
Resource Type:
Journal Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America; (USA)
Additional Journal Information:
Journal Volume: 86:8; Journal ID: ISSN 0027-8424
Country of Publication:
United States
Language:
English
Subject:
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

Citation Formats

Suits, A G, Chait, A, Aviram, M, and Heinecke, J W. Phagocytosis of aggregated lipoprotein by macrophages: Low density lipoprotein receptor-dependent foam-cell formation. United States: N. p., 1989. Web. doi:10.1073/pnas.86.8.2713.
Suits, A G, Chait, A, Aviram, M, & Heinecke, J W. Phagocytosis of aggregated lipoprotein by macrophages: Low density lipoprotein receptor-dependent foam-cell formation. United States. https://doi.org/10.1073/pnas.86.8.2713
Suits, A G, Chait, A, Aviram, M, and Heinecke, J W. 1989. "Phagocytosis of aggregated lipoprotein by macrophages: Low density lipoprotein receptor-dependent foam-cell formation". United States. https://doi.org/10.1073/pnas.86.8.2713.
@article{osti_5443211,
title = {Phagocytosis of aggregated lipoprotein by macrophages: Low density lipoprotein receptor-dependent foam-cell formation},
author = {Suits, A G and Chait, A and Aviram, M and Heinecke, J W},
abstractNote = {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.},
doi = {10.1073/pnas.86.8.2713},
url = {https://www.osti.gov/biblio/5443211}, journal = {Proceedings of the National Academy of Sciences of the United States of America; (USA)},
issn = {0027-8424},
number = ,
volume = 86:8,
place = {United States},
year = {Sat Apr 01 00:00:00 EST 1989},
month = {Sat Apr 01 00:00:00 EST 1989}
}