A CD36-initiated Signaling Cascade Mediates Inflammatory Effects of β-Amyloid

β-Amyloid accumulation is associated with pathologic changes in the brain in Alzheimer's disease and has recently been identified in plaques of another chronic inflammatory disorder, atherosclerosis. The class B scavenger receptor, CD36, mediates binding of fibrillar β-amyloid to cells of the...

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Bibliographic Details
Published in:The Journal of biological chemistry Vol. 277; no. 49; p. 47373
Main Authors: Kathryn J. Moore, Joseph El Khoury, Lea A. Medeiros, Kinya Terada, Changiz Geula, Andrew D. Luster, Mason W. Freeman
Format: Journal Article
Language:English
Published: American Society for Biochemistry and Molecular Biology 06-12-2002
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Summary:β-Amyloid accumulation is associated with pathologic changes in the brain in Alzheimer's disease and has recently been identified in plaques of another chronic inflammatory disorder, atherosclerosis. The class B scavenger receptor, CD36, mediates binding of fibrillar β-amyloid to cells of the monocyte/macrophage lineage, including brain macrophages (microglia). In this study, we demonstrate that in microglia and other tissue macrophages, β-amyloid initiates a CD36-dependent signaling cascade involving the Src kinase family members, Lyn and Fyn, and the mitogen-activated protein kinase, p44/42. Interruption of this signaling cascade, through targeted disruption of Src kinases downstream of CD36, inhibits macrophage inflammatory responses to β-amyloid, including reactive oxygen and chemokine production, and results in decreased recruitment of microglia to sites of amyloid deposition in vivo . The finding that engagement of CD36 by β-amyloid initiates a Src kinase-dependent production of inflammatory mediators in cells of the macrophage lineage reveals a novel receptor-mediated pro-inflammatory signaling pathway of potential therapeutic importance.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M208788200