The urokinase receptor is overexpressed in the AIDS dementia complex and other neurological manifestations
The urokinase receptor is overexpressed in the AIDS dementia complex and other neurological manifestations
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DOI：
10.1002/ana.20076
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发表时间：
2004-05-01
影响因子：
11.2
通讯作者：
Sidenius, N
中科院分区：
文献类型：
--
作者：
Cinque, P;Nebuloni, M;Sidenius, N
尿激酶型纤溶酶原激活物（uPA）及其受体（uPAR）在中枢神经系统（CNS）细胞外基质降解和细胞迁移中起重要作用。为了研究uPA/uPAR系统在获得性免疫缺陷综合征痴呆综合征（ADC）病理生理学中的作用，我们检测了人类免疫缺陷病毒（HM-1）感染患者和对照组脑脊液（CSF）和血浆中可溶性uPAR（suPAR）水平。无论HIV-1疾病分期如何，HIV-1感染患者的CSF suPAR水平显著高于对照组，ADC或机会性CNS感染（CNS-OI）患者的CSF suPAR水平显著高于神经系统无症状患者。最高水平的suPAR被发现在ADC的患者，并在与CNS-OI的巨细胞病毒脑炎或隐球菌病患者。血浆suPAR水平在HIV-1感染的患者高于对照组，并增加与HIV-1疾病的阶段，无论是否存在中枢神经系统疾病。在ADC或CNS-OI患者中，CSF suPAR水平与CSF HIV-1 RNA相关，但与血浆suPAR浓度无关。高效抗逆转录病毒治疗与CSF suPAR和HIV-1 RNA的显著平行降低相关。在HIV-I脑炎患者的脑组织中，uPAR在小胶质细胞和多核巨细胞中高度表达，HIV-1染色呈阳性。uPAR在ADC患者中枢神经系统的过度表达提示uPA/uPAR系统可能参与了ADC的组织损伤和神经元损伤。
The urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an important role in extracellular matrix degradation and cell migration in the central nervous system (CNS). To investigate the role of the uPA/uPAR system in the pathophysiology of acquired immunodeficiency syndrome dementia complex (ADC), we measured soluble uPAR (suPAR) levels in cerebrospinal fluid (CSF) and plasma from human immunodeficiency virus (HM-1-infected patients and controls. CSF suPAR levels were significantly higher in HIV-1-infected patients than in controls and in patients with ADC or opportunistic CNS infections (CNS-OIs) than in neurologically asymptomatic patients, irrespective of HIV-1 disease stage. The highest levels of suPAR were found in patients with ADC, and among those with CNS-OIs in patients with cytomegalovirus encephalitis or cryptococcosis. Plasma suPAR levels were higher in HIV-1-infected patients than in controls and increased with HIV-1 disease stage regardless of the presence of CNS disease. In patients with ADC or CNS-OIs, CSF suPAR levels correlated with CSF HIV-1 RNA, but not with plasma suPAR concentrations. Highly active antiretroviral therapy was associated with a significant and parallel decrease of both CSF suPAR and HIV-1 RNA. In brain tissue from patients with HIV-I encephalitis, uPAR was highly expressed by microglial and multinucleated giant cells staining positively for HIV-1. The overexpression of uPAR in the CNS of patients with ADC suggests that the uPA/uPAR system may contribute to the tissue injury and neuronal damage in this disease.