Abstract
Autoantibodies and complement opsonization have been implicated in the process of demyelination in the major human CNS demyelinating disease multiple sclerosis (MS), but scavenger receptors (SRs) may also play pathogenetic roles. We characterized SR mRNA and protein expression in postmortem brain tissue from 13 MS patients in relation to active demyelination. CD68, chemokine (C-X-C motif) ligand 16 (CXCL16), class A macrophage SR (SR-AI/II), LOX-1 (lectin-like oxidized low-density lipoprotein receptor 1), FcγRIII, and LRP-1 (low-density lipoprotein receptor-related protein 1) mRNA were upregulated in the rims of chronic active MS lesions. CD68 and CXCL16 mRNA were also upregulated around chronic active MS lesions. By immunohistochemistry, CD68, CXCL16, and SR-AI/II were expressed by foamy macrophages in the rim and by ramified microglia around chronic active MS lesions. CXCL16 and SR-AI/II were also expressed by astrocytes in MS lesions and by primary human microglia and astrocytes in vitro. These data suggest that SRs are involved in myelin uptake in MS, and that upregulation of CD68, CXCL16, and SR-AI/II is one of the initial events in microglia as they initiate myelin phagocytosis. As demyelination continues, additional upregulation of LOX-1, FcγRIII, and LRP-1 may facilitate this process.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Antigens, CD / metabolism
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Astrocytes / metabolism
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Brain / metabolism*
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Brain / pathology
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Calcium-Binding Proteins
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Chemokine CXCL16
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Chemokines, CXC / metabolism
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DNA-Binding Proteins / metabolism
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Demyelinating Diseases / etiology
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Demyelinating Diseases / pathology*
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Female
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Glial Fibrillary Acidic Protein / metabolism
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HLA-D Antigens / metabolism
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Humans
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Laser Capture Microdissection
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Low Density Lipoprotein Receptor-Related Protein-1 / metabolism
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Male
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Microfilament Proteins
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Microglia / metabolism
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Middle Aged
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Multiple Sclerosis / complications
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Multiple Sclerosis / pathology*
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Myelin Proteolipid Protein / metabolism
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RNA, Messenger / metabolism
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Receptors, Scavenger / classification
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Receptors, Scavenger / genetics
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Receptors, Scavenger / metabolism*
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Scavenger Receptors, Class E / genetics
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Scavenger Receptors, Class E / metabolism
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Statistics as Topic
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Up-Regulation*
Substances
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AIF1 protein, human
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Antigens, CD
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CXCL16 protein, human
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Calcium-Binding Proteins
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Chemokine CXCL16
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Chemokines, CXC
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DNA-Binding Proteins
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Glial Fibrillary Acidic Protein
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HLA-D Antigens
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LRP1 protein, human
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Low Density Lipoprotein Receptor-Related Protein-1
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Microfilament Proteins
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Myelin Proteolipid Protein
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OLR1 protein, human
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RNA, Messenger
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Receptors, Scavenger
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Scavenger Receptors, Class E