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...
Saved in:
Published in: | The Journal of biological chemistry Vol. 277; no. 49; p. 47373 |
---|---|
Main Authors: | , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
American Society for Biochemistry and Molecular Biology
06-12-2002
|
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
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 |