STIMULATION OF MONOCYTIC ENDOTHELIN-1 PRODUCTION BY HIV-1 GP120

单核/巨噬细胞在人类肿瘤的发病机制中起关键作用， 免疫缺陷病毒（HIV）感染，作为目标的病毒 复制和多功能细胞因子的产生来源。 内皮素，具有强有力的血管收缩活性的肽，最初 从内皮细胞分离，也产生和分泌， 与其他细胞因子类似的方式抑制巨噬细胞。 中 为了探索内皮素在HIV感染中的潜在作用，我们 研究了HIV-1包膜糖蛋白gp 120对 单核细胞内皮素-1生成。 这种糖蛋白已被鉴定为 作为单核因子如TNF-α和白细胞介素-6的有效刺激剂， 其被认为是HIV脑病的潜在介质。 我们发现gp 120与LPS类似，刺激细胞的分泌， 内皮素-1以及TNF-α从巨噬细胞在一个 浓度依赖性。 使用逆转录聚合酶 链反应（RT PCR），我们发现循环单核细胞在 HIV感染者表现出内皮素-1的不同表达 在健康对照中检测不到的基因，表明慢性 在HIV感染中激活该基因。 此外，脑 HIV脑病患者巨噬细胞强阳性 内皮素 因此，单核细胞内皮素似乎受到刺激， 在HIV感染期间。 它们强大的血管活性使它们 潜在的候选人介导脑灌注的改变 与艾滋病痴呆综合症有关的模式。

Monocytes/macrophages play a critical role in the pathogenesis of human immunodeficiency virus (HIV) -infection, both as targets f or virus replication and sources of production of multifunctional cytokines. Endothelins, peptides with potent vasoconstricting activities, originally isolated from endothelial cells, are also produced and secreted by macrophages in a manner similar to that of other cytokines. In an attempt to explore the potential role of endothelins in HIV-infection, we investigated the effect of the HIV-1 envelope glycoprotein, gpl20, on monocytic endothelin-1 production. This glycoprotein has been identified as a potent stimulator of monokines such as TNF-alpha and interleukin-6, which have been implicated as potential mediators of HIV-encephalopathy. We found that gpl20, similar to LPS, stimulates the secretion of endothelin-1 as well as TNF-alpha from macrophages in a concentration-dependent manner. Using reverse transcriptase polymerase chain reaction (RT PCR), we found that circulating monocytes in HIV-infected individuals show a distinct expression of the endothelin-1 gene which is not detectable in healthy controls, indicating chronic activation of this gene in HIV-infection. In addition, cerebral macrophages in patients with HIV-encephalopathy were strongly positive for endothelin. Thus, monocytic endothelins appear to be stimulated during HIV-infection. Their potent vasoactive properties render them potential candidates for mediating alterations in the cerebral perfusion pattern associated with the AIDS dementia complex.