| First Author | Moore KJ | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 49 | Pages | 47373-9 |
| PubMed ID | 12239221 | Mgi Jnum | J:80658 |
| Mgi Id | MGI:2446750 | Doi | 10.1074/jbc.M208788200 |
| Citation | Moore KJ, et al. (2002) A CD36-initiated signaling cascade mediates inflammatory effects of beta-amyloid. J Biol Chem 277(49):47373-9 |
| abstractText | beta-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 beta-amyloid to cells of the monocyte/macrophage lineage, including brain macrophages (microglia). In this study, we demonstrate that in microglia and other tissue macrophages, beta-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 beta-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 beta-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. |
