Macrophage uptake of low-density lipoprotein modified by 4-hydroxynonenal. An ultrastructural study
- Cleveland Clinic Foundation, OH (USA)
We have documented the ultrastructural characteristics of the uptake and processing by mouse peritoneal macrophages (MPM) of low-density lipoprotein (LDL) modified with 4-hydroxynonenal (HNE), an intermediate of lipid peroxidation. This was performed as part of a larger biochemical study assessing the role of LDL oxidation in lipid loading of macrophages during atherogenesis. Gold-labeled LDL that was modified with HNE leading to particle aggregation represented the morphologic probe used. When incubated with MPM, the probe became associated with short segments of cell membrane, probably derived from blebs or from lysed cells. At 37 degrees C there was a time-dependent increase in uptake by MPM, and at 4 hours the increase paralleled the degradation by MPM of 125I-labeled HNE-LDL-cAu. Clathrin-coated pits on the cell surface were consistently associated with probe. Uptake of probe appeared to occur via phagocytosis, because pseudopods frequently surrounded probe, and cytochalasin D quantitatively prevented probe uptake. A time-dependent increase was found in the number of gold particles per unit area within vacuoles, some of which were secondary lysosomes, based on acid phosphatase-positive staining. Thus, HNE-induced aggregation of LDL during oxidation, binding of aggregates to clathrin-coated pits on MPM, and subsequent phagocytosis may represent one of the ways lipid-laden foam cells are formed in vivo.
- OSTI ID:
- 5961482
- Journal Information:
- Laboratory Investigation (A Journal of Experimental Methods and Pathology); (USA), Vol. 64:2; ISSN 0023-6837
- Country of Publication:
- United States
- Language:
- English
Similar Records
Stimulation of mast cells leads to cholesterol accumulation in macrophages in vitro by a mast cell granule-mediated uptake of low density lipoprotein
Reduced cellular redox status induces 4-hydroxynonenal-mediated caspase 3 activation leading to erythrocyte death during chronic arsenic exposure in rats
Related Subjects
LIPOPROTEINS
MEMBRANE TRANSPORT
MACROPHAGES
PHAGOCYTOSIS
CELL MEMBRANES
IODINE 125
METABOLISM
MICE
PERITONEUM
TIME DEPENDENCE
TRACER TECHNIQUES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIPIDS
MAMMALS
MEMBRANES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PHAGOCYTES
PROTEINS
RADIOISOTOPES
RODENTS
SEROUS MEMBRANES
SOMATIC CELLS
VERTEBRATES
550501* - Metabolism- Tracer Techniques