Elevation of CD69+ monocyte/macrophages in patients with Alzheimer's disease

Elevation of CD69+ monocyte/macrophages in patients with Alzheimer's disease
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DOI:
10.1016/s0171-2985(00)80049-2
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发表时间:
2000-05-01
期刊:
影响因子:
2.8
通讯作者:
Pulliam, L
Pulliam, L
中科院分区:
医学4区
文献类型:
--
作者:
Kusdra, L;Rempel, H;Pulliam, L

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在这份报告中,我们检查了阿尔茨海默病 (AD) 患者的单核细胞上是否存在激活标记 CD69。我们之前已经表明,艾滋病痴呆患者的 CD14(+)/CD69(+) 亚群比例较高,并且来自这些 M/M phi 培养物的条件培养基对神经培养物具有毒性。因此,我们假设 AD 患者可能同样具有较高的单核细胞亚群,这可能与神经毒性有关。流量分析显示,AD 患者 (n = 13) 的 CD69(+) M/M phi 比例高于年龄匹配的对照组 (n = 14);这一趋势具有统计学意义(p = 0.006)。 AD 患者的侧向散射 (SSC)(衡量细胞粒度的指标)也有所升高 (p = 0.02)。人类白细胞抗原 (HLA-DR) 表达的升高在年龄匹配的对照者和 AD 患者之间没有发现显着性。当对来自五名 AD 患者和两名对照患者的 M/M phi 条件培养基进行神经毒性评估时,来自 AD 患者的五名培养物上清液中的三名在神经细胞聚集体培养物中诱导细胞凋亡。电泳迁移率变动分析揭示了这一点。这三种上清液还引发了 NF-kappa B 易位至细胞核。令人惊讶的是,具有较低百分比的CD14(+)/CD69(+)细胞的M/M phi上清液在体外诱导神经毒性。因此,AD患者中CD14(+)/CD69(+)子集的升高可能代表脑部发生的病理事件在外周血中的表现,但可能并不直接参与神经细胞毒性。
In this report, we examined the presence of the activation marker, CD69, on monocytes derived from patients with Alzheimer's disease (AD). We have previously shown that patients with AIDS dementia had an elevated percentage of a CD14(+)/CD69(+) subset and that conditioned media from these M/M phi cultures were toxic to neural cultures. We therefore postulated that patients with AD might likewise have a higher monocyte subset and that this would be associated with neural toxicity. Flow analysis showed that AD patients (n = 13) had a higher percentage of CD69(+) M/M phi over age matched controls (n = 14); this trend was statistically significant (p = 0.006). Side scatter (SSC), a measure of cellular granularity was also elevated in AD patients (p = 0.02). The elevated expression of human leukocyte antigen (HLA-DR) was not found to be significant between age-matched controls and AD patients. when conditioned media from M/M phi From five AD and two control patients were evaluated fur neurotoxicity three of the five culture supernatants from AD patients induced apoptosis in neural cell aggregate cultures. Electrophoretic mobility shift assays revealed that. these three supernatants also triggered NF-kappa B translocation to the nucleus. Surprisingly, in vitro a neurotoxicity was induced by M/M phi supernatants having a lower percentage of CD14(+)/CD69(+) cells. Elevation of the CD14(+)/CD69(+) subset in AD patients may therefore represent a manifestation in the peripheral blood of the pathological events occurring in the brain bur may nor be directly involved in neural cell toxicity.