FAS ANTIGEN EXPRESSION ON CD34(+) HUMAN MARROW-CELLS IS INDUCED BY INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR-ALPHA AND POTENTIATES CYTOKINE-MEDIATED HEMATOPOIETIC SUPPRESSION IN-VITRO
FAS ANTIGEN EXPRESSION ON CD34(+) HUMAN MARROW-CELLS IS INDUCED BY INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR-ALPHA AND POTENTIATES CYTOKINE-MEDIATED HEMATOPOIETIC SUPPRESSION IN-VITRO
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DOI：
10.1182/blood.v85.11.3183.bloodjournal85113183
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发表时间：
1995-06-01
期刊：
影响因子：
20.3
通讯作者：
YOUNG, NS
中科院分区：
文献类型：
--
作者：
MACIEJEWSKI, J;SELLERI, C;YOUNG, NS
Fas 抗原（一种细胞表面受体分子）通过其配体激活，导致细胞死亡信号的转导。 fas 系统与靶细胞识别、免疫效应细胞的克隆发育以及细胞免疫反应的终止有关。淋巴细胞上的Fas抗原表达受到干扰素γ（IFNγ）和肿瘤坏死因子α（TNFα）的调节，这些细胞因子对造血也有抑制作用，我们在体外研究了人骨髓细胞上的Fas抗原表达以及Fas激活对造血的影响，新鲜分离的未成熟造血细胞， 根据 CD34 标记物的定义，Fas 抗原的表达水平可通过荧光染色检测到，CD34(+) 细胞（包括祖细胞和干细胞）即使在存在生长因子的情况下，在培养物中也显示出低水平的 Fas 表达，TNF α 和 IFN γ 的刺激显着增加了 CD34(+) 细胞上的 Fas 抗原表达，抗 Fas 抗体模拟了假定的作用 配体，以剂量依赖性方式增强 IFN γ 和 TNF α 介导的对骨髓 (BM) 集落形成的抑制。这种效应不需要辅助细胞的存在，在存在 IFN γ 和 TNF α 的情况下，成熟 (CD34(+) CD38(+)) 和未成熟 (CD34(+) CD38(-)) 祖细胞和长期培养起始细胞的集落形成对抗 fas 抗体的抑制作用敏感。对总BM细胞和CD34(+)细胞进行的凋亡测定表明，抗fas抗体诱导CD34(+)BM细胞的程序性细胞死亡。 Fas抗原可以作为造血细胞分化程序的一部分表达。 Fas 抗原及其配体可能在骨髓衰竭状态的病理生理学以及免疫反应过程中消除异常造血细胞中发挥作用。 (C) 1995 年，美国血液学会。
Activation of Fas antigen, a cell surface receptor molecule, by its ligand results in transduction of a signal for cell death. The fas system has been implicated in target cell recognition, clonal development of immune effector cells, and termination of the cellular immune response. Fas antigen expression on lymphocytes is regulated by interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha), cytokines that also have inhibitory effects on hematopoiesis, We investigated Fas antigen expression on human marrow cells and the effects of Fas activation on hematopoiesis in vitro, Freshly isolated immature hematopoietic cells, as defined by the CD34 marker, did not express Fas antigen at levels detectable by fluorescent staining, CD34(+) cells, which include progenitors and stem cells, showed low levels of Fas expression in culture, even in the presence of growth factors, Stimulation by TNF alpha and IFN gamma markedly increased Fas antigen expression on CD34(+) cells, Anti-Fas antibody, which mimics the action of the putative ligand, enhanced IFN gamma- and TNF alpha-mediated suppression of colony formation by bone marrow (BM) in a dose-dependent manner. This effect did not require the presence of accessory cells, Colony formation from mature (CD34(+) CD38(+)) and immature (CD34(+) CD38(-)) progenitor cells and long-term culture initiating cells were susceptible to the inhibitory action of anti-fas antibody in the presence of IFN gamma and TNF alpha. Apoptosis assays performed on total BM cells and CD34(+) cells showed that anti-fas antibody induced programmed cell death of CD34(+) BM cells. Fas antigen may be expressed as part of the differentiation program of hematopoietic cells. Fas antigen and its ligand may play a role in the pathophysiology of marrow failure states and in the elimination of abnormal hematopoietic cells in the course of an immune response. (C) 1995 by The American Society of Hematology.