Minghetti L, Hughes P, Perry V H
Laboratory of Pathophysiology, Istituto Superiore di Sanità, Rome, Italy.
Neuroscience. 1999;92(4):1405-15. doi: 10.1016/s0306-4522(98)00739-8.
The expression of cyclooxygenase-2, a key enzyme in prostaglandin and thromboxane synthesis in inflammation, was studied immunohistochemically in in vivo models of acute and chronic inflammatory responses in rat central nervous system. In the acute inflammatory response to intracranial injection of heat-killed bacillus Calmette-Guérin as well as in the immune-mediated, delayed-type hypersensitivity response to the same pathogen, cyclooxygenase-2 expression was restricted to major infiltrating haematogenous cell populations such as neutrophils and mononuclear phagocytes, while the expression of the enzyme by brain non-neuronal resident cells (astrocytes, microglia, perivascular cells) appeared to be limited to perivascular cells of the blood vessels in the vicinity of the lesion and in the surrounding area. On the basis of their morphology and location, these perivascular cells were identified as perivascular macrophages, but we could not rule out the possibility that some endothelial cells also expressed cyclooxygenase-2. The constitutive neuronal cyclooxygenase-2 was not affected by the ongoing inflammation. Interestingly, in spite of the extensive astrocyte and microglial reaction occurring over a broad area surrounding the inflammatory lesions, there was no obvious cyclooxygenase-2 staining in these cells. These data indicate that the up-regulation of cyclooxygenase-2 expression in acute and chronic, immune-mediated lesions in the brain parenchyma is remarkably restricted to the lesion site. Since cyclooxygenase metabolites can regulate important functions of resident as well as infiltrating cells, the increased synthesis of prostaglandins and thromboxanes, which is likely to occur as a consequence of the expression of cycloxygenase-2 at the lesion site, might represent an important component of the inflammatory processes within the brain.
环氧化酶-2是炎症中前列腺素和血栓素合成的关键酶，本研究采用免疫组织化学方法，在大鼠中枢神经系统急性和慢性炎症反应的体内模型中，对其表达情况进行了研究。在对颅内注射热灭活卡介苗的急性炎症反应以及对同一病原体的免疫介导迟发型超敏反应中，环氧化酶-2的表达仅限于主要浸润的血源性细胞群体，如中性粒细胞和单核吞噬细胞，而脑非神经元常驻细胞（星形胶质细胞、小胶质细胞、血管周围细胞）中该酶的表达似乎仅限于病变附近及周围区域血管的血管周围细胞。根据其形态和位置，这些血管周围细胞被鉴定为血管周围巨噬细胞，但我们不能排除某些内皮细胞也表达环氧化酶-2的可能性。组成型神经元环氧化酶-2不受正在进行的炎症影响。有趣的是，尽管在炎症病变周围的广泛区域发生了广泛的星形胶质细胞和小胶质细胞反应，但这些细胞中没有明显的环氧化酶-2染色。这些数据表明，在脑实质急性和慢性免疫介导病变中环氧化酶-2表达的上调明显局限于病变部位。由于环氧化酶代谢产物可以调节常驻细胞和浸润细胞的重要功能，病变部位环氧化酶-2表达可能导致的前列腺素和血栓素合成增加，可能是脑内炎症过程的一个重要组成部分。
