CD36 mediates the innate host response to β-amyloid

被引:407
作者
El Khoury, JB
Moore, KJ
Means, TK
Leung, J
Terada, K
Toft, M
Freeman, MW
Luster, AD
机构
[1] Harvard Univ, Ctr Immunol & Inflammatory Dis, Sch Med, Massachusetts Gen Hosp,Div Rheumatol Allergy & Im, Charlestown, MA USA
[2] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA
[3] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lipid Met Unit, Charlestown, MA 02129 USA
[4] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, Charlestown, MA 02129 USA
关键词
microglia; scavenger receptor; Alzheimer's disease; chemokine; reactive oxygen species; MACROPHAGE SCAVENGER RECEPTOR; NITRIC-OXIDE SYNTHASE; ALZHEIMERS-DISEASE; REACTIVE MICROGLIA; TRANSGENIC MICE; SENILE PLAQUES; CELLS; EXPRESSION; ACTIVATION; MONOCYTES;
D O I
10.1084/jem.20021546
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Accumulation of inflammatory nucroglia in Alzheimer's senile plaques is a hallmark of the innate response to beta-amyloid fibrils and can initiate and propagate neurodegeneration characteristic of Alzheimer's disease (AD). The molecular mechanism whereby fibrillar beta-amyloid activates the inflammatory response has not been elucidated. CD36, a class B scavenger receptor, is expressed on nucroglia in normal and AD brains and binds to beta-amyloid fibrils in vitro. We report here that microglia and macrophages, isolated from CD36 null mice, had marked reductions in fibrillar beta-amyloid-induced secretion of cytokines, chemokines, and reactive oxygen species. Intraperitoneal and stereotaxic intracerebral injection of fibrillar beta-amyloid in CD36 null mice induced significantly less macrophage and microglial recruitment into the peritoneum and brain, respectively, than in wild-type mice. Our data reveal that CD36, a major pattern recognition receptor, mediates microglial and macrophage response to beta-amyloid, and imply that CD36 plays a key role in the proinflammatory events associated with AD.
引用
收藏
页码:1657 / 1666
页数:10
相关论文
共 33 条
  • [1] Engagement of the scavenger receptor is not responsible for β-amyloid stimulation of monocytes to a neurocytopathic state
    Antic, A
    Dzenko, KA
    Pachter, JS
    [J]. EXPERIMENTAL NEUROLOGY, 2000, 161 (01) : 96 - 101
  • [2] Basu A, 2002, J NEUROSCI, V22, P6071
  • [3] Bornemann KD, 2001, AM J PATHOL, V158, P63, DOI 10.1016/S0002-9440(10)63945-4
  • [4] Christie RH, 1996, AM J PATHOL, V148, P399
  • [5] Combs CK, 2001, J NEUROSCI, V21, P1179
  • [6] CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer's disease brains and can mediate production of reactive oxygen species in response to β-amyloid fibrils
    Coraci, IS
    Husemann, J
    Berman, JW
    Hulette, C
    Dufour, JH
    Campanella, GK
    Luster, AD
    Silverstein, SC
    El Khoury, JB
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2002, 160 (01) : 101 - 112
  • [7] DICKSON DW, 1988, AM J PATHOL, V132, P86
  • [8] Microglia, scavenger receptors, and the pathogenesis of Alzheimer's disease
    El Khoury, J
    Hickman, SE
    Thomas, CA
    Loike, JD
    Silverstein, SC
    [J]. NEUROBIOLOGY OF AGING, 1998, 19 (01) : S81 - S84
  • [9] ELKHOURY J, 1994, J BIOL CHEM, V269, P10197
  • [10] ElKhoury J, 1996, NATURE, V382, P716