Immunization with a cannabinoid receptor type 1 peptide results in experimental allergic meningocerebellitis in the Lewis rat: a model for cell-mediated autoimmune neuropathology.
Immunization with a cannabinoid receptor type 1 peptide results in experimental allergic meningocerebellitis in the Lewis rat: a model for cell-mediated autoimmune neuropathology.
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使用 1 型大麻素受体肽进行免疫会导致 Lewis 大鼠实验性过敏性脑膜小脑炎：细胞介导的自身免疫神经病理学模型。
DOI：
10.1002/jnr.10424
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发表时间：
2002
影响因子：
4.2
通讯作者：
Herkenham,Miles
中科院分区：
文献类型：
--
作者：
Proescholdt,MargitG;Quigley,Laura;Martin,Roland;Herkenham,Miles
神经元元件越来越多地被认为是某些神经系统和神经精神疾病中自身免疫攻击的主要目标。 1 型大麻素受体 (CB1) 被选为自身免疫靶点，因为它们主要在大脑神经元表面表达，并且在纹状体、海马和小脑中表现出惊人的高蛋白质水平。用大鼠 CB1 胞外结构域的 N 末端乙酰化肽（每只大鼠 50 或 400 μg）对雌性 Lewis 大鼠进行免疫，并在不同时间点处死。随后使用免疫组织化学和原位杂交进行的评估显示，免疫细胞仅在小脑内密集浸润，在使用含有氨基酸 9-25 的 CB1 肽免疫后 12-16 天达到峰值。浸润物聚集在分子和颗粒细胞层的脑膜和血管周围位置，也散布在富含 CB1 的神经纤维中。它们主要由 CD4+ 和 ED1+ 细胞组成，提示细胞介导的自身免疫病理。大脑或脊髓的其他地方没有炎症浸润。结果表明，神经元元件，例如神经元细胞表面受体，可能被识别为细胞介导的自身免疫攻击中的抗原靶标，因此支持某些脑部疾病中细胞介导的抗神经元自身免疫病理学的假设。 2002 年出版 Wiley-Liss, Inc.
Neuronal elements are increasingly suggested as primary targets of an autoimmune attack in certain neurological and neuropsychiatric diseases. Type 1 cannabinoid receptors (CB1) were selected as autoimmune targets because they are predominantly expressed on neuronal surfaces in brain and display strikingly high protein levels in striatum, hippocampus, and cerebellum. Female Lewis rats were immunized with N‐terminally acetylated peptides (50 or 400 μg per rat) of the extracellular domains of the rat CB1 and killed at various time points. Subsequent evaluation using immunohistochemistry and in situ hybridization showed dense infiltration of immune cells exclusively within the cerebellum, peaking 12–16 days after immunization with the CB1 peptide containing amino acids 9–25. The infiltrates clustered in meninges and perivascular locations in molecular and granular cell layers and were also scattered throughout the CB1‐rich neuropil. They consisted primarily of CD4+and ED1+cells, suggestive of cell‐mediated autoimmune pathology. There were no inflammatory infiltrates elsewhere in the brain or spinal cord. The results show that neuronal elements, such as neuronal cell‐surface receptors, may be recognized as antigenic targets in a cell‐mediated autoimmune attack and, therefore, support the hypothesis of cell‐mediated antineuronal autoimmune pathology in certain brain disorders. Published 2002 Wiley‐Liss, Inc.