Cannella B, Raine C S
Department of Pathology, (Neuropathology), Albert Einstein College of Medicine, Bronx, NY, USA.
Ann Neurol. 1995 Apr;37(4):424-35. doi: 10.1002/ana.410370404.
The expression of the adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), and their respective receptors on leukocytes, very late activation antigen-4 (VLA-4) and lymphocyte function-associated antigen-1 (LFA-1), together with a selection of proinflammatory and immunomodulatory cytokines (interleukin [IL]-1, IL-2, IL-4, IL-10, tumor necrosis factor-alpha [TNF-alpha], transforming growth factor-beta [TGF-beta], and interferon-gamma [IFN-gamma] was examined by immunocytochemistry in multiple sclerosis (MS) lesions of different ages and compared with central nervous system (CNS) tissue from other neurological diseases, both inflammatory and noninflammatory, and normal CNS tissue. These molecules play key roles in lymphocytic infiltration and interactions during tissue inflammation and are in large part normally not expressed by CNS cells. High levels of expression of all the molecules tested were found in MS, particularly in chronic active lesions. Positivity for all molecules was also seen in other neurological diseases, even in noninflammatory conditions. There was some suggestion that the VCAM-1/VLA-4 adhesion pathway was expressed at higher levels in chronic MS lesions, while ICAM-1/LEA-1 was used more uniformly in lesions of all ages. Of the cytokines examined, there was increased expression of TNF-alpha and IL-4 in MS; this was found to be statistically significant when compared with noninflammatory neurological diseases. The expression of most adhesion molecules and some cytokines was negligible in normal CNS tissue although low-level reactivity for ICAM-1 TGF-beta, IL-4, TNF-alpha, and IL-10 was detected, perhaps indicative of immunoregulatory mechanisms. Microglial cells and astrocytes were the major CNS cell types expressing cytokines. The results indicate a potential in the CNS for widespread induced expression of molecules involved in the inflammatory cascade. No adhesion or cytokine molecule or pattern of expression unusual for MS was apparent.
通过免疫细胞化学方法，检测了不同年龄多发性硬化（MS）病变中黏附分子血管细胞黏附分子-1（VCAM-1）和细胞间黏附分子-1（ICAM-1）及其在白细胞上各自的受体极迟活化抗原-4（VLA-4）和淋巴细胞功能相关抗原-1（LFA-1）的表达情况，并与其他炎性和非炎性神经系统疾病的中枢神经系统（CNS）组织以及正常CNS组织进行了比较。这些分子在组织炎症期间的淋巴细胞浸润和相互作用中起关键作用，并且在很大程度上正常情况下中枢神经系统细胞不表达。在MS中发现所有测试分子的表达水平都很高，尤其是在慢性活动性病变中。在其他神经系统疾病中，甚至在非炎性疾病中，所有分子也呈阳性。有迹象表明，VCAM-1/VLA-4黏附途径在慢性MS病变中的表达水平更高，而ICAM-1/LFA-1在所有年龄段的病变中使用更为一致。在所检测的细胞因子中，MS中肿瘤坏死因子-α（TNF-α）和白细胞介素-4（IL-4）的表达增加；与非炎性神经系统疾病相比，这具有统计学意义。正常CNS组织中大多数黏附分子和一些细胞因子的表达可以忽略不计，尽管检测到ICAM-1、转化生长因子-β（TGF-β）、IL-4、TNF-α和IL-10有低水平反应，这可能表明存在免疫调节机制。小胶质细胞和星形胶质细胞是表达细胞因子的主要中枢神经系统细胞类型。结果表明，中枢神经系统有广泛诱导表达参与炎症级联反应分子的潜力。未发现MS中黏附分子或细胞因子分子或表达模式有异常。
