The expression of Fas ligand by macrophages and its upregulation by human immunodeficiency virus infection
The expression of Fas ligand by macrophages and its upregulation by human immunodeficiency virus infection
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DOI：
10.1172/jci1171
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发表时间：
1998-06-01
影响因子：
15.9
通讯作者：
Paya, CV
中科院分区：
文献类型：
--
作者：
Dockrell, DH;Badley, AD;Paya, CV
Fas/Fas配体（FasL）相互作用在外周血T淋巴细胞稳态和以T细胞耗竭为特征的某些病理状态中起重要作用。在这项研究中，我们证明，抗原呈递细胞，如单核细胞衍生的人巨噬细胞（MDM），但不是单核细胞衍生的树突状细胞表达基础水平的FasL。MDM的HIV感染增加了FasL蛋白表达，而不依赖于翻译后机制，因此突出了病毒诱导的Fast转录上调。这些观察结果的体外相关性在人淋巴组织中得到证实，FasL蛋白表达是组成性的，并限于组织巨噬细胞而不是树突状细胞。在HIV（+）个体的淋巴组织中观察到巨噬细胞相关Fast显著增加（P < 0.001），这进一步得到了使用原位杂交增加的Fast mRNA水平的支持，体内Fast蛋白表达的程度与组织凋亡的程度相关（r = 0.761，P < 0.001），在HIV感染者的组织中显著增高（P < 0.001），这些结果鉴定了人组织巨噬细胞作为体外和体内Fast表达的相关来源，并突出了Fast表达的潜在作用。在HIV感染的免疫发病机制中的表达。
Fas/Fas Ligand (FasL) interactions play a significant role in peripheral T lymphocyte homeostasis and in certain pathological states characterized by T cell depletion. In this study, we demonstrate that antigen-presenting cells such as monocyte-derived human macrophages (MDM) but not monocyte-derived dendritic cells express basal levels of FasL. HIV infection of MDM increases FasL protein expression independent of posttranslational mechanisms, thus highlighting the virus-induced transcriptional upregulation of Fast, The in vitro relevance of these observations is confirmed in human lymphoid tissue, FasL protein expression is constitutive and restricted to tissue macrophages and not dendritic cells, Moreover, a significant increase in macrophage-associated Fast is observed in lymphoid tissue from HIV (+) individuals (P < 0.001), which is further supported by increased levels of Fast mRNA using in situ hybridization, The degree of Fast protein expression in vivo correlates with the degree of tissue apoptosis (r = 0.761, P < 0.001), which is significantly increased in tissue from HIV-infected patients (P < 0.001), These results identify human tissue macrophages as a relevant source for Fast expression in vitro and in vivo and highlight the potential role of Fast expression in the immunopathogenesis of HIV infection.