Bell M D, Perry V H
Department of Pharmacology, University of Oxford, UK.
J Neurocytol. 1995 Sep;24(9):695-710. doi: 10.1007/BF01179819.
The acute inflammatory response in the murine CNS is different from that observed in other tissues. Few polymorphonuclear leukocytes are recruited to the brain parenchyma and there is a delay in the recruitment of monocytes. Leukocyte recruitment to sites of inflammation is dependent on adhesion molecules expressed on the endothelium. The atypical kinetics of leukocyte recruitment to the CNS may be the result of deficient or delayed adhesion molecule expression on the cerebral endothelium. Using immunohistochemistry, the present study demonstrates that following the intracranial injection of a proinflammagen, lipopolysaccharide, or following acute neuronal degeneration elicited with kainic acid, the adhesion molecules ICAM-1 and VCAM were readily upregulated on cerebral endothelium in a time course comparable with that demonstrated on non-CNS endothelium. Both molecules were expressed on vessels, irrespective of their size, at 24 h after kainic acid or 6 h after lipopolysaccharide injection but leukocyte recruitment was negligible. The expression of ICAM-1 was demonstrated not only on endothelium but also on microglia especially in response to nerve terminal degeneration. PECAM was constitutively expressed at high levels on cerebral endothelium and did not change during brain injury. However, PECAM was induced on astrocytes after lipopolysaccharide injection or during acute neuronal degeneration, the latter providing a particularly strong stimulus. This study indicates that the expression of these adhesion molecules on CNS endothelium is neither deficient or delayed and that they are unlikely to be limiting factors in leukocyte recruitment to the CNS.
小鼠中枢神经系统中的急性炎症反应与在其他组织中观察到的不同。很少有多形核白细胞被募集到脑实质，并且单核细胞的募集存在延迟。白细胞向炎症部位的募集依赖于内皮细胞上表达的黏附分子。白细胞向中枢神经系统募集的非典型动力学可能是脑内皮细胞上黏附分子表达不足或延迟的结果。本研究通过免疫组织化学表明，在颅内注射促炎原脂多糖后，或在用 kainic 酸引发急性神经元变性后，黏附分子 ICAM-1 和 VCAM 在脑内皮细胞上很容易上调，其时间进程与在非中枢神经系统内皮细胞上所显示的相当。在 kainic 酸注射后 24 小时或脂多糖注射后 6 小时，这两种分子都在血管上表达，无论血管大小如何，但白细胞募集可以忽略不计。ICAM-1 的表达不仅在内皮细胞上显示，而且在小胶质细胞上也有表达，尤其是在对神经末梢变性的反应中。PECAM 在脑内皮细胞上持续高水平表达，在脑损伤期间没有变化。然而，在脂多糖注射后或急性神经元变性期间，星形胶质细胞上诱导了 PECAM，后者提供了特别强烈的刺激。这项研究表明，这些黏附分子在中枢神经系统内皮细胞上的表达既不缺乏也不延迟，并且它们不太可能是白细胞向中枢神经系统募集的限制因素。
