Balabanov R, Beaumont T, Dore-Duffy P
Department of Neurology, Wayne State University School of Medicine and Detroit Medical Center, Michigan 48201, USA.
J Neurosci Res. 1999 Mar 1;55(5):578-87. doi: 10.1002/(SICI)1097-4547(19990301)55:5<578::AID-JNR5>3.0.CO;2-E.
The cellular constituents of the blood-brain barrier (BBB) must make finely tuned, regulatory responses to maintain microvascular homeostasis. The mechanisms by which this task is accomplished are largely unknown. However, it is thought they involve a series of cross-talk mechanisms among endothelial cells (EC), pericytes (PC), and astrocytes. During inflammation, the BBB is exposed to a number of biological response modifiers including cytokines released by infiltrating leukocytes. The response to inflammatory cytokines may alter the normal regulatory function of EC and PC. These changes may account for some of the pathological findings in central nervous system (CNS) inflammatory disease. Previous studies have shown that PC and EC may have immune potential. We have investigated the response of the PC to a variety of inflammatory cytokines. Primary rat PC constitutively express low levels of intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) class I molecule, which can be upregulated in response to the cytokine interferon-gamma (IFNgamma). IFNgamma also induced the expression of MHC class II molecule. After induction of MHC class II molecule, CNS PC acquired the capacity to present antigen to primed syngeneic rat T-lymphocytes. Antigen presentation by PC was comparable to that seen with classic antigen-presenting cells. A small number of primary PC constitutively express low levels of vascular cell adhesion molecule-1 (VCAM-1), which was increased on exposure to tumor necrosis factor-alpha (TNFalpha). Results suggest that CNS PC respond to inflammatory cytokines, are involved in T-lymphocyte activation, and express cell surface adhesion molecules (VCAM-1, ICAM-1) that may provide costimulatory activity. It is likely that CNS PC are important in neuroimmune networks at the BBB.
血脑屏障（BBB）的细胞成分必须做出精确调节的反应，以维持微血管的稳态。完成这项任务的机制在很大程度上尚不清楚。然而，人们认为它们涉及内皮细胞（EC）、周细胞（PC）和星形胶质细胞之间的一系列相互作用机制。在炎症过程中，血脑屏障会接触到多种生物反应调节剂，包括浸润白细胞释放的细胞因子。对炎性细胞因子的反应可能会改变内皮细胞和周细胞的正常调节功能。这些变化可能解释了中枢神经系统（CNS）炎性疾病中的一些病理发现。先前的研究表明，周细胞和内皮细胞可能具有免疫潜能。我们研究了周细胞对多种炎性细胞因子的反应。原代大鼠周细胞组成性表达低水平的细胞间黏附分子-1（ICAM-1）和主要组织相容性复合体（MHC）I类分子，这些分子可因细胞因子γ干扰素（IFNγ）而被上调。IFNγ还诱导了MHC II类分子的表达。在诱导MHC II类分子后，中枢神经系统周细胞获得了向致敏的同基因大鼠T淋巴细胞呈递抗原的能力。周细胞的抗原呈递与经典抗原呈递细胞的情况相当。少数原代周细胞组成性表达低水平的血管细胞黏附分子-1（VCAM-1），在暴露于肿瘤坏死因子-α（TNFα）时其水平会升高。结果表明，中枢神经系统周细胞对炎性细胞因子有反应，参与T淋巴细胞激活，并表达可能提供共刺激活性的细胞表面黏附分子（VCAM-1、ICAM-1）。中枢神经系统周细胞很可能在血脑屏障的神经免疫网络中起重要作用。
