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Low density lipoprotein uptake by macrophages in multiple sclerosis plaques: implications for pathogenesis
1Multiple Sclerosis Laboratory, Institute of Neurology, London, UK.
Neuropathology and Applied Neurobiology
|April 1, 1994
Summary
Low density lipoprotein (LDL) enters multiple sclerosis (MS) lesions, where it becomes oxidized. This oxidized LDL and myelin debris are taken up by macrophages, potentially driving demyelination.
Area of Science:
- Neuroimmunology
- Pathology
- Biochemistry
Background:
- Low density lipoprotein (LDL) is the primary plasma cholesterol carrier.
- Blood-brain barrier damage in multiple sclerosis (MS) allows LDL entry into brain parenchyma.
- Oxidative modification of LDL is implicated in various disease processes.
Purpose of the Study:
- To investigate the presence and modification of LDL within MS lesions.
- To determine the source of lipids in foamy macrophages within MS plaques.
- To explore the role of oxidized LDL in MS pathogenesis.
Main Methods:
- Immunocytochemical staining of MS plaques using antibodies against native LDL and oxidized LDL (MDA-LDL, 4-HNE-LDL).
- Co-localization studies with myelin basic protein and neutral lipid staining (Oil Red O).
- Polarized light microscopy to identify cholesterol esters (Maltese crosses).
Main Results:
- Native LDL and oxidized LDL epitopes were found in foamy macrophages within early and active MS plaques.
- Cholesterol esters in foamy macrophages originated from both LDL and myelin.
- Astrocytes showed uptake of oxidized LDL components, independent of neutral lipids.
Conclusions:
- A significant portion of LDL entering MS lesions undergoes oxidative modification.
- Oxidized LDL uptake by microglia and macrophages may contribute to demyelination in early MS.
- Lipid peroxidation and oxidized LDL are implicated in the pathogenesis of MS plaques.