MECHANISMS FOR HIV-1 ENHANCEMENT OF EICOSANOID FORMATION

HIV感染伴随着前列腺素水平的升高， 可以通过抑制淋巴因子的产生来调节免疫功能，T细胞 功能，T、B细胞增殖。全长GP-120 分离纯化了在CHO细胞中表达的重组蛋白。GP-120 刺激大鼠星形胶质细胞K+通道活性并诱导 细胞黏附分子ICAM在原代培养细胞中的表达 星形胶质细胞。一种与CD4受体结合的抗体(OKT4A) 刺激单核细胞产生前列腺素和细胞因子。 OKT4A显著促进p56lck自动磷酸化，而CHO表达 GP-120使p56lck酪氨酸磷酸化水平略有增加。 THP-1细胞和THP-1细胞向巨噬细胞分化的研究 TPA处理与GP-120、OKT4A或内毒素(一种已知的 单核/巨噬细胞中PGHS-2表达的刺激因子)。既有全科医生- 120和OKT4A抗体均不能增加 花生四烯酸或前列腺素的形成。西部和北部 分析表明，这些单核细胞中存在PGHS-1。LP 刺激TPA处理的大鼠PGHS-2mRNA和蛋白表达增加 细胞，但不在单核细胞中。前列腺素HS-1和-2蛋白的表达 而对照或TPA的孵育不能增加消息传递。 用GP-120或OKT4A抗体诱导分化细胞。这个 观察到GP-120制剂和/或OKT4A具有生物 在其他系统中的活性，不会促进前列腺素的形成 人类单核/巨噬细胞的相互作用提供了证据 与CD4受体结合的包膜蛋白不是导致 在HIV-1感染者中观察到前列腺素的增加。

HIV infection is accompanied by elevated levels of prostaglandins which can modulate immune function by inhibiting lymphokine production, T-cell function, and T and B cell proliferation. The full length gp-120 recombinant expressed in CHO cells was isolated and purified. The gp-120 stimulated K+ channel activity in rat astrocytes and induced the expression of the cell adhesion molecule, ICAM, in primary cultures of astrocytes. An antibody (OKT4A) which binds to the CD4 receptor stimulates the formation of prostaglandins and cytokines from monocytes. OKT4A greatly enhanced p56lck autophosphorylation while the CHO expressed gp-120 produced a marginal increase in p56lck tyrosine phosphorylation. THP-1 cells and THP-1 cells induced to differentiate into macrophages by TPA treatment were incubated with gp-120, OKT4A or LPS (a known stimulator of PGHS-2 expression in monocytes/macrophages). Both the gp- 120 and the OKT4A antibody failed to increase either the release of arachidonic acid or the formation of prostaglandins. Western and Northern analysis indicated the presence of PGHS-1 in these monocytes. LPS stimulated an increase in PGHS-2 mRNA and protein in the TPA-treated cells but not in the monocytes. The expression of PGHS-1 and -2 protein and message was not increased by incubation of the control or TPA- differentiated cells with either the gp-120 or OKT4A antibody. The observation that gp-120 preparations and/or OKT4A, which have biological activity in other systems, do not enhance prostaglandin formation in human monocytes/macrophages provides evidence that the interaction of the envelope protein with the CD4 receptor is not responsible for the increase in prostaglandins observed in HIV-1 infected persons.