Dugas N, Lacroix C, Kilchherr E, Delfraissy J F, Tardieu M
Laboratoire Virus, Neurone et Immunité, Faculté de Médecine Paris Sud, 63 rue Gabriel Péri, 94276 Le Kremlin Bicêtre, France.
Cytokine. 2001 Jul 21;15(2):96-107. doi: 10.1006/cyto.2001.0896.
Soluble factors released by intra-cerebral activated cells are implicated in neuronal alterations during central nervous system inflammatory diseases. In this study, the role of the CD23 pathway in astrocyte activation and its participation in human immunodeficiency virus-1 (HIV-1)-induced neuropathology were evaluated. In human primary astrocytes, CD23 protein membrane expression was dose-dependently upregulated by gp120. It was also upregulated by gamma-interferon (gamma-IFN) and modulated by interleukin-1-beta (IL-1beta) whereas microglial cells in these stimulation conditions did not express CD23. Cell surface stimulation of CD23 expressed by astrocytes induced production of nitric oxide (NO) and IL-1beta which was inhibited by a specific inducible NO-synthase (iNOS) inhibitor (aminoguanidine), indicating the implication of this receptor in the astrocyte inflammatory reaction. On brain tissues from five out of five patients with HIV-1-related encephalitis, CD23 was expressed by astrocytes and by some microglial cells, whereas it was not detectable on brain tissue from five of five HIV-1-infected patients without central nervous system (CNS) disease or from two of two control subjects. In addition, CD23 antigen was co-localized with iNOS and nitrotyrosine on brain tissue from patients with HIV1-related encephalitis, suggesting that CD23 participates in iNOS activation of astrocytes in vivo. In conclusion, CD23 ligation is an alternative pathway in the induction of inflammatory product synthesis by astrocytes and participates in CNS inflammation.
脑内活化细胞释放的可溶性因子与中枢神经系统炎性疾病期间的神经元改变有关。在本研究中，评估了CD23途径在星形胶质细胞活化中的作用及其在人类免疫缺陷病毒1型（HIV-1）诱导的神经病理学中的参与情况。在人原代星形胶质细胞中，gp120可剂量依赖性地上调CD23蛋白的膜表达。γ干扰素（γ-IFN）也可上调其表达，白细胞介素-1β（IL-1β）可对其进行调节，而在这些刺激条件下小胶质细胞不表达CD23。星形胶质细胞表达的CD23的细胞表面刺激可诱导一氧化氮（NO）和IL-1β的产生，一种特异性诱导型NO合酶（iNOS）抑制剂（氨基胍）可抑制这种产生，这表明该受体参与了星形胶质细胞的炎症反应。在5例HIV-1相关性脑炎患者的脑组织中，星形胶质细胞和一些小胶质细胞表达CD23，而在5例无中枢神经系统（CNS）疾病的HIV-1感染患者或2例对照受试者的脑组织中未检测到CD23。此外，在HIV-1相关性脑炎患者的脑组织中，CD23抗原与iNOS和硝基酪氨酸共定位，提示CD23在体内参与星形胶质细胞的iNOS活化。总之，CD23连接是星形胶质细胞诱导炎性产物合成的另一条途径，并参与CNS炎症。
