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有毒槲寄生凝集素在人淋巴细胞中诱导Fas配体(CD95L)的产生。

Induction of Fas ligand (CD95L) by the toxic mistletoe lectins in human lymphocytes.

作者信息

Büssing A, Stein G M, Pfüller U, Schietzel M

机构信息

Department of Applied Immunology, University Witten/Herdecke, Communal Hospital, Germany.

出版信息

Anticancer Res. 1999 May-Jun;19(3A):1785-90.

PMID:10470116
Abstract

BACKGROUND

Fas ligand (FasL, CD95L) predominantly expressed on activated cytotoxic T cells and NK cells triggers apoptosis in Fas receptor (Apo-1, CD95) positive target cells. We investigated the expression of FasL, Fas and tumor necrosis factor (TNF) receptor 1 (TNF-R1, CD120a) on cultured human lymphocytes and leukemic T and B cells.

MATERIALS AND METHODS

Lymphocytes from six healthy individuals, from four patients with chronic lymphocytic T or B cell leukaemia, and leukemic Molt-4 cells were incubated with the apoptosis- inducing mistletoe lectins (ML I and ML III).

RESULTS

Incubation of differentiated lymphocytes with the ML resulted in a significant upregulation of FasL in the surviving CD4+ T helper cells, CD8+ cells and CD19+ B cells. Similarly, the TNF receptor expression increased, while the Fas molecule decreased. In contrast, FasL was not induced in leukemic cells.

CONCLUSIONS

Apart from a direct induction of apoptosis in response to an inhibition of protein synthesis by the enzymic ML A chain, ML treatment may indirectly induce apoptosis in Fas+ tumour cells through activated FasL+ lymphocytes.

摘要

背景

主要表达于活化的细胞毒性T细胞和自然杀伤细胞上的Fas配体(FasL,CD95L)可触发Fas受体(Apo-1,CD95)阳性靶细胞的凋亡。我们研究了培养的人淋巴细胞、白血病T细胞和B细胞上FasL、Fas和肿瘤坏死因子(TNF)受体1(TNF-R1,CD120a)的表达情况。

材料与方法

将来自6名健康个体、4名慢性淋巴细胞性T或B细胞白血病患者的淋巴细胞以及白血病Molt-4细胞与诱导凋亡的槲寄生凝集素(ML I和ML III)一起孵育。

结果

用ML孵育分化的淋巴细胞后,存活的CD4⁺辅助性T细胞、CD8⁺细胞和CD19⁺B细胞中FasL显著上调。同样,TNF受体表达增加,而Fas分子减少。相反,白血病细胞中未诱导出FasL。

结论

除了通过ML的酶A链抑制蛋白质合成直接诱导凋亡外,ML治疗可能通过活化的FasL⁺淋巴细胞间接诱导Fas⁺肿瘤细胞凋亡。

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