Cyclooxygenase-2-positive macrophages infiltrate the Alzheimer's disease brain and damage the blood-brain barrier
Cyclooxygenase-2-positive macrophages infiltrate the Alzheimer's disease brain and damage the blood-brain barrier
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DOI：
10.1046/j.1365-2362.2002.00994.x
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发表时间：
2002-05-01
影响因子：
5.5
通讯作者：
Vinters, HV
中科院分区：
文献类型：
--
作者：
Fiala, M;Liu, QN;Vinters, HV
研究背景：单核/巨噬细胞在HIV-1脑炎（HIVE）患者脑内浸润，在阿尔茨海默病（AD）患者脑内，活化的小胶质细胞的来源尚未确定。和共聚焦显微镜，以确定巨噬细胞和小胶质细胞与淀粉样蛋白β斑块和血液-结果在两种疾病中，环氧合酶2阳性的巨噬细胞以及少量的T和B细胞浸润脑血管周围间隙和神经胶质细胞。巨噬细胞可与分枝的小胶质细胞区分开，并在内皮紧密连接蛋白ZO-1明显破坏的部位装饰血管。巨噬细胞。也浸润β淀粉样蛋白斑块，显示细胞内β淀粉样蛋白，并被无β淀粉样蛋白的腔隙包围。此外，在淀粉样血管病中，巨噬细胞部分包围含淀粉样β蛋白的血管壁，并表现出细胞内淀粉样β蛋白，但不表现出细胞旁腔隙。与AD组织相比，HIVE脑组织中微血管周围的纤维蛋白原渗漏区域明显更大（P = 0.034），并且AD组织的渗漏明显大于对照组织（P = 0.0339）。AD组CD 68（P= 0.03）和COX-2免疫反应阳性细胞（P = 0.004）所占面积均明显高于正常对照组。结论在HIVE和AD中，血源性活化的单核/巨噬细胞和淋巴细胞均能通过破坏的血脑屏障迁移。β淀粉样蛋白斑块中巨噬细胞周围的腔隙而不是血管壁中的腔隙与巨噬细胞吞噬和清除体外β淀粉样蛋白沉积物的能力一致。
Background Monocyte/macrophages are known to infiltrate the brain of patients with HIV-1 encephalitis (HIVE), In Alzheimer's disease brain, the origin of activated microglia has not been determined.Materials and methods We employed the antigen retrieval technique, immunocytochemistry, immunofluorescense, and confocal microscopy to identify macrophages and microglia in relation to amyloid-beta plaques and the blood-brain barrier in autopsy brain tissues from patients with Alzheimer's disease (AD) and HIVE.Results In both conditions, cyclooxygenase-2 positive macrophages and, to a lesser degree, T and B cells infiltrate brain perivascular spaces and neuropil. The macrophages are distinguishable from ramified microglia, and decorate the vessels at the sites of apparent of endothelial tight junction protein ZO-1 disruption. The macrophages. also infiltrate amyloid-beta plaques, display intracellular amyloid-beta and are surrounded by amyloid-D-free lacunae. Furthermore, the macrophages partially encircle the walls of amyloid-p-containing vessels in amyloid angiopathy, and exhibit intracellular amyloid-beta but not paracellular lacunae. Significantly larger zones of fibrinogen leakage surround the microvessels in HIVE brain tissues compared with AD tissues (P = 0.034), and AD tissues have significantly greater leakage than control tissues (P = 0.0339). The AD group differs from a normal control age-matched group with respect to both the area occupied by CD68 (P= 0.03) and cyclooxygenase-2 immunoreactive cells (P = 0.004).Conclusion In both HIVE and AD, blood-borne activated monocyte/macrophages and lymphocytes appear to migrate through a disrupted blood-brain barrier. The lacunae around macrophages in amyloid-beta plaques but not in vessel walls are consistent with the ability of macrophages to phagocytize and clear amyloid-beta deposits in vitro.