Expression of a cytokeratin 18 neo-epitope is a specific marker for trophoblast apoptosis in human placenta

Expression of a cytokeratin 18 neo-epitope is a specific marker for trophoblast apoptosis in human placenta
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DOI:
10.1053/plac.2000.0616
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发表时间:
2001-01-01
期刊:
影响因子:
3.8
通讯作者:
Huppertz, B
Huppertz, B
中科院分区:
医学3区
文献类型:
--
作者:
Kadyrov, M;Kaufmann, P;Huppertz, B

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在上皮细胞中,凋亡期间细胞角蛋白18的半胱天冬酶介导的切割导致形成由抗体M30识别的特异性新表位。为了测试这种抗体是否可以用作凋亡滋养层细胞的特异性标志物,我们用抗细胞角蛋白7和18的抗体,抗活性半胱天冬酶3的抗体,用M30和TUNEL反应对早孕和晚孕人胎盘的绒毛和交界区的连续切片进行染色。M30免疫反应性与TUNEL阳性和细胞角蛋白7和18的免疫反应性的比较清楚地表明,M30特异性标记晚期凋亡滋养层细胞。这一发现得到以下事实的支持:在滋养层中,M30免疫反应性与活性半胱天冬酶3的免疫反应性在很大程度上重叠。与TUNEL试验相比,M30免疫反应似乎是凋亡滋养层的高度可重复的标志物。与TUNEL反应相比,该抗体染色细胞凋亡级联中的大量细胞,因为细胞角蛋白18裂解比DNA裂解更早开始,并且因为在一些滋养层细胞中可以绕过核酸内切酶活化。数据表明,M30上级TUNEL反应作为检测滋养层细胞凋亡的标志物,因为它更容易处理,对细胞凋亡更特异,更不易产生伪影。(C)2001年哈考特出版社有限公司
In epithelial cells the caspase-mediated cleavage of cytokeratin 18 during apoptosis leads to the formation of a specific neo-epitope, recognized by the antibody M30. To test whether this antibody can be used as a specific marker for apoptotic trophoblast, we have stained serial sections of villi and junctional zone of first and third trimester human placenta with antibodies against cytokeratins 7 and 18, and against active caspase 3, with M30 and with the TUNEL reaction. Comparison of M30 immunoreactivities with TUNEL positivity and immunoreactivities for cytokeratins 7 and 18 clearly demonstrates that M30 specifically labels late apoptotic trophoblast cells. This finding is supported by the fact that in trophoblast, M30 immunoreactivities largely overlap with those for active caspase 3. As compared to the TUNEL test, the M30 immune reaction appears to be a highly reproducible marker for apoptotic trophoblast. This antibody stains a larger number of cells within the apoptosis; cascade as compared to the TUNEL reaction, since cytokeratin 18 cleavage starts earlier than cleavage of DNA and since endonuclease activation can be bypassed in some trophoblast cells. The data suggest that M30 is superior to the TUNEL reaction as a marker for the detection of trophoblast apoptosis since it is easier to handle, more specific for apoptosis and less prone to artifacts. (C) 2001 Harcourt Publishers Ltd.