Kiener P A, Davis P M, Rankin B M, Klebanoff S J, Ledbetter J A, Starling G C, Liles W C
Immunological Diseases, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121, USA.
J Immunol. 1997 Aug 15;159(4):1594-8.
Human monocytes express both Fas and Fas ligand (FasL) on the cell surface, and the interaction of these molecules induces spontaneous apoptosis. In this report we present a study of monocytic cells by FACS and confocal microscopy using anti-FasL Abs that reveals high levels of preformed FasL within the intracellular compartment. Further analysis by immunoblotting of cell cytoplasmic proteins confirmed the presence of a 37-kDa protein recognized by anti-FasL Abs. Stimulation of the monocytic cells with immune complexes, PHA, or superantigen gave rise to the rapid release of soluble FasL from within the cells. The presence of high levels of FasL within human monocytes suggests that, upon stimulation, the cells can rapidly translocate intracellular FasL to the cell surface and release it into the extracellular milieu. These findings indicate a novel mechanism for monocytes to respond rapidly to environmental changes, resulting in the release of active, soluble FasL.
人类单核细胞在细胞表面表达Fas和Fas配体(FasL),这些分子的相互作用诱导自发性凋亡。在本报告中,我们使用抗FasL抗体通过流式细胞术和共聚焦显微镜对单核细胞进行了研究,结果显示细胞内区室中存在高水平的预先形成的FasL。通过对细胞质蛋白进行免疫印迹的进一步分析证实了存在一种可被抗FasL抗体识别的37 kDa蛋白。用免疫复合物、PHA或超抗原刺激单核细胞会导致细胞内可溶性FasL的快速释放。人类单核细胞中存在高水平的FasL表明,在受到刺激时,细胞可以迅速将细胞内的FasL转运至细胞表面并释放到细胞外环境中。这些发现揭示了单核细胞对环境变化做出快速反应的一种新机制,从而导致活性可溶性FasL的释放。