Role of ICAM-1 in persisting inflammation in Parkinson disease and MPTP monkeys
Role of ICAM-1 in persisting inflammation in Parkinson disease and MPTP monkeys
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DOI：
10.1016/j.expneurol.2005.10.034
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发表时间：
2006-02-01
影响因子：
5.3
通讯作者：
McGeer, PL
中科院分区：
文献类型：
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作者：
Miklossy, J;Doudet, DD;McGeer, PL
已经确定帕金森病 (PD) 病例的黑质 (SN) 中存在神经炎症，但造成的因素尚不清楚。一种贡献蛋白可能是细胞间粘附分子-1（ICAM-1、CD54）。已知 ICAM-1 及其反受体淋巴细胞功能相关抗原 1 (LFA-1) 在炎症过程和 T 细胞介导的宿主防御机制中发挥关键作用。我们在 14 名经神经病理学确诊的 PD 患者（其中 3 名有家族血统）的 SN 中检测到大量 ICAM-1 阳性反应性星形胶质细胞，与 11 名年龄匹配的对照患者相比。在 PD SN 中，这些 ICAM-1 阳性反应性星形胶质细胞特别集中在神经元严重丢失和细胞外黑色素积累区域的许多残留神经元周围。 LFA-1 阳性反应性小胶质细胞聚集在 ICAM-1 表达强烈的区域，并且发现 LFA-1 阳性白细胞浸润组织。 ICAM-1 和 LFA-1 的双重免疫染色揭示了反应性小胶质细胞的聚集，嵌入弥漫性 ICAM-1 区域。与对照组相比，PD SN 中的白细胞计数高 5 倍（P < 0.001）。与对照猴相比，在 5.5 至 14 年前接触过 MPTP 的猴子中也发现了类似的 ICAM-I 过度表达。帕金森病和 MPTP 治疗的猴子中 TCAM-1 阳性反应性星形胶质细胞的存在表明持续的炎症过程，并表明抗炎药物可能在帕金森病治疗中占有一席之地。 (c) 2005 Elsevier Inc. 保留所有权利。
It has been established that neuroinflamination is present in the substantia nigra (SN) of Parkinson disease (PD) cases but the factors responsible are as yet unknown. One contributing protein may be the intercellular adhesion molecule-1 (ICAM-1, CD54). ICAM-1 with its counter receptor, the lymphocyte function-associated antigen 1 (LFA-1) is known to play a key role in inflammatory processes and in T-cell mediated host defense rnechanisms. We detected large numbers of ICAM-1-positive reactive astrocytes in the SN of a series of 14 patients with neuropathologically confirmed PD, including 3 of familial origin, compared with 11 age-matched controls. In PD SN, these ICAM-1-positive reactive astrocytes were particularly concentrated around many residual neurons in areas of heavy neuronal loss and extracellular melanin accumulation. LFA-1-positive reactive microglia gathered in areas of intense ICAM-1 expression, and LFA-1-positive leukocytes were identified infiltrating the tissue. Double immunostaining for ICAM-1 and LFA-1 revealed aggregates of reactive microglia, embedded in areas of diffuse ICAM-1. Leukocyte counts were 5 fold higher in PD SN compared to controls (P < 0.001). Similar over-expression of ICAM-I was found in monkeys that had been exposed to MPTP from 5.5 to 14 years previously compared with control monkeys. The presence of TCAM-1-positive reactive astrocytes in Parkinson disease and MPTP-treated monkeys is indicative of a sustained inflammatory process and suggests that antiinflammatory agents may have a place in PD therapy. (c) 2005 Elsevier Inc. All rights reserved.