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反应性星形胶质细胞中膜联蛋白 A1 的上调及其在人脑梗死边界处的微量诱导。

Upregulation of Annexin A1 in Reactive Astrocytes and Its Subtle Induction in Microglia at the Boundaries of Human Brain Infarcts.

机构信息

Department of Neuropathology.

Department of Medicine and Clinical Science.

出版信息

J Neuropathol Exp Neurol. 2019 Oct 1;78(10):961-970. doi: 10.1093/jnen/nlz079.

DOI:10.1093/jnen/nlz079
PMID:31504683
Abstract

Annexin A1 (ANXA1) has multiple functions, including anti-inflammatory effects, and is thought to be neuroprotective in various pathophysiologies of the central nervous system. The importance of ANXA1 in microglia and endothelial cells in ischemic environments in the brain has been recognized, but its detailed behavior in astrocytes in the ischemic brain remains unknown. Using immunohistochemistry, we therefore assessed the altered distribution of ANXA1 in human brain infarcts using 14 autopsied samples and 18 surgical samples. Elevated expression of ANXA1 was observed in reactive astrocytes in peri-infarct regions. ANXA1 accumulated at the cell periphery and in swollen cytoplasmic processes of reactive astrocytes, as well as at the rim of vacuoles at the boundary of necrosis, and colocalized with aberrantly distributed aquaporin 4 and excitatory amino acid transporter 1. Foamy macrophages in the necrotic core also expressed abundant ANXA1, whereas resident microglia at the boundary of necrosis rarely showed intrinsic expression of ANXA1. This characteristic distribution of ANXA1 in human brain infarcts may represent the good adaptability of reactive astrocytes to ischemic damage.

摘要

膜联蛋白 A1(ANXA1)具有多种功能,包括抗炎作用,并且被认为在中枢神经系统的各种病理生理中具有神经保护作用。已经认识到 ANXA1 在脑缺血环境中的小胶质细胞和内皮细胞中的重要性,但它在缺血性脑星形胶质细胞中的详细行为仍不清楚。因此,我们使用免疫组织化学方法,使用 14 个尸检样本和 18 个手术样本评估了 ANXA1 在人类脑梗死中的改变分布。在梗死周围区域的反应性星形胶质细胞中观察到 ANXA1 的表达升高。ANXA1 聚集在反应性星形胶质细胞的细胞外周和肿胀的细胞质突起中,以及坏死边界处空泡的边缘,并且与异常分布的水通道蛋白 4 和兴奋性氨基酸转运蛋白 1 共定位。坏死核心中的泡沫状巨噬细胞也表达大量的 ANXA1,而坏死边界处的固有微胶质细胞很少表现出内在的 ANXA1 表达。ANXA1 在人类脑梗死中的这种特征性分布可能代表反应性星形胶质细胞对缺血性损伤的良好适应性。

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