Actinobacillus actinomycetemcomitans induces apoptosis of T lymphocytes by the Fas and Fas ligand pathway.
Actinobacillus actinomycetemcomitans induces apoptosis of T lymphocytes by the Fas and Fas ligand pathway.
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Actinobacillus actinomycetemcomitans 通过 Fas 和 Fas 配体途径诱导 T 淋巴细胞凋亡。
DOI：
10.1034/j.1399-302x.2002.170503.x
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发表时间：
2002
影响因子：
--
通讯作者：
Zadeh,HH
中科院分区：
文献类型：
--
作者：
Nalbant,A;Zadeh,HH
伴生放线杆菌表达多种能够诱导T淋巴细胞凋亡的毒素。然而，确切的机制(S)尚未阐明。本研究探讨了Fas(CD95)介导的细胞凋亡途径INA的参与。伴生放线菌诱导T细胞凋亡。为此，外周血单个核细胞(PBMC)在有或没有培养液的情况下培养。放线菌无细胞培养上清液(CFCs)培养0~96 h，用特异性单抗标记细胞，进行流式细胞仪检测。结果显示，在TOA反应中，T细胞Fas表达上调，caspase-3激活。放线菌伴生CFCS。单核细胞是唯一被分析为组成性表达Fas配体(FasL)的细胞，并且这一表达在TOA反应中进一步上调。放线菌伴随CFCS，而T细胞只有在此刺激后才表达FasL。单核细胞在a刺激前的耗竭。伴放线菌CFCS诱导的细胞凋亡率明显下降。用抗Fas单抗或Fas：Fc融合蛋白阻断Fas-FasL相互作用可显著降低T细胞的凋亡率，但不能完全消除T细胞的凋亡。几乎所有的T细胞在培养开始时都表达Bcl2，在a刺激的T细胞中Bcl2的表达下降。放线菌伴生CFCS。总而言之，这些数据为YA诱导T细胞凋亡提供了证据。放线菌通过Fas介导的途径参与caspase-3和bcl2的凋亡反应。而且，这种凋亡反应依赖于单核细胞的存在。
Actinobacillus actinomycetemcomitansexpresses a number of toxins capable of inducing apoptotic cell death of T lymphocytes. However, the exact mechanism(s) has not been elucidated. The present study investigated the involvement of the Fas (CD95)‐mediated apoptotic pathway inA. actinomycetemcomitans‐induced T‐cell apoptosis. To that end, peripheral blood mononuclear cells (PBMC) were cultured with or withoutA. actinomycetemcomitanscell‐free culture supernatant (CFCS) for 0–96 h. The cells were then labeled with specific monoclonal antibodies and flow cytometry was performed. Results demonstrated up‐regulation of Fas and activation of caspase‐3 in T cells in response toA. actinomycetemcomitansCFCS. Monocytes were the only cells analyzed to express Fas ligand (FasL) constitutively, and this was further up‐regulated in response toA. actinomycetemcomitansCFCS, while T cells expressed FasL only after this stimulation. Depletion of monocytes prior to stimulation withA. actinomycetemcomitansCFCS led to a marked decline in apoptosis. Blocking of Fas–FasL interactions with anti‐Fas monoclonal antibody or Fas:Fc fusion protein lead to a significant decline, but not abolition, of T‐cell apoptosis. Nearly all T cells expressed Bcl‐2 at the outset of culture, and Bcl‐2 expression declined in T cells stimulated withA. actinomycetemcomitansCFCS. Collectively, these data provide evidence for the induction of T‐cell apoptosis byA. actinomycetemcomitansvia the Fas‐mediated pathway, involving caspase‐3 and Bcl‐2. Moreover, this apoptotic response was dependent on the presence of monocytes.
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