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
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
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DOI：
10.1016/s0002-9440(10)64354-4
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发表时间：
2002-01-01
影响因子：
6
通讯作者：
El Khoury, JB
中科院分区：
文献类型：
--
作者：
Coraci, IS;Husemann, J;El Khoury, JB
阿尔茨海默病的病理标志是老年斑，由β-淀粉样原纤维、小胶质细胞、星形胶质细胞和营养不良的神经突组成。我们之前报道过，A 类清道夫受体介导小胶质细胞和巨噬细胞对 β-淀粉样原纤维和氧化低密度脂蛋白 (oxLDL) 涂层表面的粘附。我们还表明，CD36（一种 B 类清道夫受体和 oxLDL 受体）可促进粘附于 oxLDL 包被表面的巨噬细胞分泌 H2O2。 CD36 是否在小胶质细胞上表达，以及它是否在小胶质细胞与纤维状 β-淀粉样蛋白相互作用分泌 H2O2 中发挥作用尚不清楚。使用荧光激活细胞分选分析和免疫组织化学，我们发现 CD36 在人胎儿小胶质细胞和 N9 永生化小鼠小胶质细胞上表达。我们还发现阿尔茨海默病患者大脑中的小胶质细胞和血管内皮细胞上有 CD36 表达。 Bowes 人黑色素瘤细胞通常不表达 CD36，当用编码人 CD36 的 cDNA 转染时，获得了与纤维状 β-淀粉样蛋白包被的表面特异性结合的能力，表明 CD36 是纤维状 β-淀粉样蛋白的受体。此外，两种不同的 CD36 单克隆抗体可抑制 N9 小胶质细胞和粘附于纤维状 β-淀粉样蛋白的人巨噬细胞产生的 H2O2，抑制程度接近 50%。我们的数据确定了 CD36 在小胶质细胞纤维状 β-淀粉样蛋白诱导的 H2O2 产生中的作用，并暗示 CD36 可以介导与纤维状 β-淀粉样蛋白的结合。我们认为，与巨噬细胞与 oxLDL 相互作用中的作用类似，A 类清道夫受体和 CD36 在小胶质细胞与纤维状 β-淀粉样蛋白的相互作用中发挥互补作用。
A pathological hallmark of Alzheimer's disease is the senile plaque, composed of beta-amyloid fibrils, microglia, astrocytes, and dystrophic neurites. We reported previously that class A scavenger receptors mediate adhesion of microglia and macrophages to beta-amyloid fibrils and oxidized low-density lipoprotein (oxLDL)coated surfaces. We also showed that CD36, a class B scavenger receptor and an oxLDL receptor, promotes H2O2 secretion by macrophages adherent to oxLDL-coated surfaces. Whether CD36 is expressed on microglia, and whether it plays a role in secretion of H2O2 by microglia interacting with fibrillar beta-amyloid is not known. Using fluorescence-activated cell sorting analysis and immunohistochemistry, we found that CD36 is expressed on human fetal microglia, and N9-immortalized mouse microglia. We also found that CD36 Is expressed on microglia and on vascular endothelial cells in the brains of Alzheimer's disease patients. Bowes human melanoma cells, which normally do not express CD36, gained the ability to specifically bind to surfaces coated with fibrillar beta-amyloid when transfected with a cDNA encoding human CD36, suggesting that CD36 is a receptor for fibrillar beta-amyloid. Furthermore, two different monoclonal antibodies to CD36 Inhibited H2O2, production by N9 microglia and human macrophages adherent to fibrillar beta-amyloid by similar to50%. Our data identify a role for CD36 in fibrillar beta-amyloid-induced H2O2 production by microglia, and imply that CD36 can mediate binding to fibrillar beta-amyloid. We propose that similar to their role in the interaction of macrophages with oxLDL, class A scavenger receptors and CD36 play complimentary roles in the interactions of microglia with fibrillar beta-amyloid.