Human immunodeficiency virus-associated changes in signal transduction.
Human immunodeficiency virus-associated changes in signal transduction.
复制标题
人类免疫缺陷病毒相关的信号转导变化。
DOI：
10.1007/bf00915060
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发表时间：
1987
影响因子：
9.1
通讯作者：
Vayuvegula,B
中科院分区：
文献类型：
--
作者：
Gupta,S;Vayuvegula,B
有丝分裂原/抗原激活T淋巴细胞的同时伴随着细胞内游离钙([Ca+]i)的升高、膜电位的改变、肌醇磷脂的代谢和蛋白激酶C的激活。信号转导的早期事件最终导致淋巴细胞激活的晚期事件，即DNA合成、淋巴因子的产生和细胞增殖。在这项研究中，我们研究了人类免疫缺陷病毒(HIV)对膜电位和[Ca~(2+)]水平的影响。感染HIV的T细胞系(H9/HTLV IIIb)膜电位显著降低(去极化)，对植物血凝素(PHA)或抗T_3(抗CD3)单抗不能正常反应。H9/HTLV IIIb细胞的基础[Ca~(2+)]水平较H9细胞升高，但经PHA或抗T_3单抗激活后，H9/HTLV IIIb细胞的[Ca~(2+)]_i几乎没有进一步升高。这与类似刺激后H9细胞内[Ca~(2+)]i显著升高形成鲜明对比。这些数据显示了慢性感染HIV的T细胞质膜电位和[Ca2+]水平的异常。T细胞激活途径信号转导的这些异常可能是HIV感染患者T细胞功能障碍的原因。
It is well established that the activation of T lymphocytes by mitogen/antigen is accompanied by a rise in intracellular free calcium ([Ca2+]i), changes in membrane potential, metabolism of inositol phospholipid, and activation of protein kinase C. Theseearly eventsof signal transduction culminate inlate eventsof lymphocyte activation, namely, DNA synthesis, lymphokine production, and cellular proliferation. In this study we examined the effect of human immunodeficiency virus (HIV) on changes in membrane potential and [Ca2+]ilevels. The membrane potentials were markedly decreased (depolarized) in T cell lines infected with HIV (H9/HTLV IIIb) and did not respond normally to phytohemagglutinin (PHA) or anti-T3 (anti-CD3) monoclonal antibody compared to uninfected H9 cell line. The basal [Ca2+]ilevels in H9/HTLV IIIb cells were increased in comparison to those in H9 cells; however, there was very little further increase in [Ca2+]iin H9/HTLV IIIb cells following activation with PHA or anti-T3 monoclonal antibody. This is in contrast to a significant rise in [Ca2+]iin H9 cells following similar stimulation. These data demonstrate abnormalities in the plasma membrane potential and [Ca2+]ilevels in chronically infected T cells with HIV. These abnormalities in signal transduction of the T-cell activation pathway could be responsible for T-cell dysfunction in patients with HIV infection.