Expression of scavenger receptor class B, type I, by astrocytes and vascular smooth muscle cells in normal adult mouse and human brain and in Alzheimer's disease brain.
In Alzheimer's disease (AD), fibrillar beta-amyloid protein (fAbeta) accumulates in the walls of cerebral vessels associated with vascular smooth muscle cells (SMCs), endothelium, and pericytes, and with microglia and astrocytes in plaques in the brain parenchyma. Scavenger receptor class A (SR-A) and class B, type I (SR-BI) mediate binding and ingestion of fAbeta by cultured human fetal microglia, microglia from newborn mice, and by cultured SMCs. Our findings that SR-BI participates in the adhesion of cultured microglia from newborn SR-A knock-out mice to fAbeta-coated surfaces, and that microglia secrete reactive oxygen species when they adhere to these surfaces prompted us to explore expression of SR-BI in vivo. We report here that astrocytes and SMCs in normal adult mouse and human brains and in AD brains express SR-BI. In contrast, microglia in normal adult mouse and human brains and in AD brains do not express SR-BI. These findings indicate that SR-BI may mediate interactions between astrocytes or SMCs and fAbeta, but not of microglia and fAbeta, in AD, and that expression of SR-BI by rodent microglia is developmentally regulated. They suggest that SR-BI expression also is developmentally regulated in human microglia.
Columbia University, College of Physicians and Surgeons, Department of Physiology and Cellular Biophysics, 630 West 168th Street, New York, NY 10032, USA. jh577@columbia.edu
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Husemann
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SC
Silverstein
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000918:Antibody Specificity; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D018955:CD36 Antigens / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D050356:Lipid Metabolism; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D016874:Neurofibrillary Tangles / Q000378:metabolism; D011817:Rabbits; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B
D016229:Amyloid beta-Peptides; D018955:CD36 Antigens; D016207:Cytokines; C495139:MSR1 protein, human; D008565:Membrane Proteins; C495140:Msr1 protein, mouse; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B