Sippy B D, Hofman F M, Wallach D, Hinton D R
Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033, USA.
J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Dec 15;10(5):511-21.
Tumor necrosis factor (TNF)-alpha has been shown to be increased in brain tissue of AIDS patients and may function as a mediator of cerebral damage. We initiated a study to determine the cellular localization and degree of protein and mRNA expression of the two specific TNF-alpha receptors (TNF-Rs), p55 and p75, in brain tissues from AIDS patients. Cerebral white matter obtained at autopsy from 13 AIDS patients, 10 unhealthy controls, and 4 healthy controls was evaluated. Double-label immunohistochemistry revealed prominent up-regulation of p55 and p75 TNF-Rs on activated macrophages and microglial cells in all AIDS patients; no increased staining was found on astrocytes. Staining was most prominent in patients with opportunistic infection of the brain and in microglial nodules of patients with HIV encephalitis. Brain tissues also showed increased expression of interleukin (IL)-1 beta, IL-6, and TNF-alpha, cytokines known to up-regulate the TNF-Rs. Increased staining for TNF-Rs was also found in patients with multiple sclerosis, chronic cerebral edema, and radiation necrosis but not in an asymptomatic HIV-positive patient without AIDS. Reverse transcriptase polymerase chain reaction performed on adjacent sections from five AIDS patients revealed up-regulation from normal for p55 in all patients and for p75 in three patients. The up-regulation of both TNF-Rs in AIDS suggests that macrophages and microglial cells may be important in amplifying the TNF-alpha response.
肿瘤坏死因子（TNF）-α在艾滋病患者脑组织中呈升高状态，可能是脑损伤的介质。我们开展了一项研究，以确定两种特异性TNF-α受体（TNF-Rs），即p55和p75，在艾滋病患者脑组织中的细胞定位、蛋白质和mRNA表达程度。对13例艾滋病患者、10例非健康对照者以及4例健康对照者尸检时获取的脑白质进行了评估。双重免疫组织化学显示，所有艾滋病患者的活化巨噬细胞和小胶质细胞上p55和p75 TNF-Rs显著上调；星形胶质细胞上未见染色增加。在脑部有机会性感染的患者以及患有HIV脑炎患者的小胶质结节中染色最为明显。脑组织还显示白细胞介素（IL）-1β、IL-6和TNF-α表达增加，这些细胞因子已知可上调TNF-Rs。在多发性硬化症、慢性脑水肿和放射性坏死患者中也发现TNF-Rs染色增加，但在无艾滋病的无症状HIV阳性患者中未发现。对5例艾滋病患者相邻切片进行的逆转录聚合酶链反应显示，所有患者p55均较正常上调，3例患者p75上调。艾滋病中两种TNF-Rs均上调表明巨噬细胞和小胶质细胞在放大TNF-α反应中可能起重要作用。
