Shed membrane fragment modulation of CD3-zeta during pregnancy: link with induction of apoptosis
Shed membrane fragment modulation of CD3-zeta during pregnancy: link with induction of apoptosis
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DOI：
10.1016/s0165-0378(02)00025-6
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发表时间：
2002-07-01
影响因子：
3.4
通讯作者：
Taylor, DD
中科院分区：
文献类型：
--
作者：
Gercel-Taylor, C;O'Connor, SM;Taylor, DD
我们的目的是鉴定母体循环中脱落的胎盘质膜片段，并确定这些片段是否能够下调CD 3-zeta链表达并诱导T淋巴细胞凋亡。将从妊娠26-29周的孕妇血液中分离的血清进行高排除限凝胶层析以分离胎盘膜片段，所述孕妇随后具有无并发症的足月分娩。胎盘型碱性磷酸盐的存在证实了胎盘来源的片段。进一步分析这些脱落的膜片段中Fas配体（FasL）的存在和培养的T淋巴细胞（Jurkat细胞）上CD 3-ζ表达的调节。使用细胞死亡ELISA测定脱落的膜片段诱导细胞凋亡的能力。与Fas依赖性细胞凋亡（caspase-3，bcl-2和bax）的组件进行了表征，使用Western免疫印迹暴露后，血清衍生的膜片段。在所有妊娠血清中均发现胎盘膜碎片，但在非妊娠对照组中未发现。在膜片段分离物中鉴定了41 kDa FasL，并且如通过ELISA测定所确定的，所有样品都能够诱导细胞凋亡。T淋巴细胞暴露于分离的膜片段抑制了CD 3-zeta的表达。细胞凋亡的诱导与caspase 3的诱导和激活以及bax的诱导有关。母体循环中可检测到胎盘源性膜碎片。这些膜片段分离物能够诱导FasL介导的凋亡和下调CD 3-zeta表达，这可能有助于胎儿的免疫耐受。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Our objective was to identify shed placental plasma membrane fragments in the maternal Circulation and determine whether these fragments are capable of down-regulating CD3-zeta chain expression and inducing apoptosis in T lymphocytes. Sera, isolated from the blood of pregnant women at 26-29 weeks gestation that subsequently had uncomplicated term deliveries, were Subjected to high exclusion-limit gel chromatography to isolate placental membrane fragments. The placental origin of the fragments was confirmed by the presence of placental-type alkaline phosphates. These shed membrane fragments were further analyzed for the presence of Fas ligand (FasL) and modulation of CD3-zeta expression on cultured T-lymphocytes (Jurkat cells). The ability of the shed membrane fragments to induce apoptosis was assayed using a cell death ELISA. Components associated with Fas-dependent apoptosis (caspase-3, bcl-2 and bax) were characterized using western immunoblot following exposure to serum-derived membrane fragments. Placental membrane fragments were identified in all pregnancy sera, but not in non-pregnant controls. The 41 kDa FasL was identified in membrane fragment isolates and all samples were capable of inducing apoptosis as determined by the ELISA assay. Exposure of T lymphocytes to isolated membrane fragments suppressed the expression of CD3-zeta. The induction of apoptosis correlated with the induction and activation of caspase 3 and the induction of bax. Placenta-derived membrane fragments are detectable in the maternal circulation. These membrane fragment isolates are capable of inducing FasL-mediated apoptosis and down-regulating CD3-zeta expression, which may contribute to the immune tolerance of the fetus. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.