Cytoprotection of Human Umbilical Vein Endothelial Cells Against Apoptosis and CTL-Mediated Lysis Provided by Caspase-Resistant Bcl-2 Without Alterations in Growth or Activation Responses1
Cytoprotection of Human Umbilical Vein Endothelial Cells Against Apoptosis and CTL-Mediated Lysis Provided by Caspase-Resistant Bcl-2 Without Alterations in Growth or Activation Responses1
复制标题
Caspase 抗性 Bcl-2 提供的人脐静脉内皮细胞针对细胞凋亡和 CTL 介导的裂解的细胞保护作用，且不改变生长或激活反应1
作者：
Lian Zheng;T. Dengler;Martin S Kluger;L. Madge;J. Schechner;S. Maher;J. Pober;A. Bothwell
移植内皮细胞是急性同种异体移植排斥反应中宿主ctl介导的损伤的主要目标。作为一项基因治疗减少ctl介导的内皮损伤的体外试验，我们稳定地用抗凋亡基因Bcl-2的caspase抗性突变形式（D34A）转导早期传代HUVEC。Bcl-2转导剂与与增强型绿色荧光蛋白（EGFP）基因并行转导的HUVEC进行了比较。两种转染的HUVEC在完全培养基中均具有相同的生长速率，且均表现出接触抑制生长。然而，与egfp转导的HUVEC相比，bcl -2转导的细胞对血清和生长因子戒断的凋亡作用具有抗性，并且对staurosporine或神经酰胺诱导的凋亡也具有抗性，无论是否有TNF。转导的Bcl-2不降低tnf介导的NF-κB活化或I类MHC分子的组成性表达。与表达EGFP的HUVEC相比，表达D34A Bcl-2的HUVEC对i类限制性同种异体反应或pha重定向CTL的裂解具有更强的抗性。我们得出结论，用D34A Bcl-2转导移植内皮细胞是减少同种异体移植排斥反应的可能途径。
Graft endothelial cells are primary targets of host CTL-mediated injury in acute allograft rejection. As an in vitro trial of gene therapy to reduce CTL-mediated endothelial injury, we stably transduced early passage HUVEC with a caspase-resistant mutant form (D34A) of the anti-apoptotic gene Bcl-2. Bcl-2 transductants were compared with HUVEC transduced in parallel with an enhanced green fluorescent protein (EGFP) gene. Both transduced HUVEC have equivalent growth rates in complete medium and both show contact inhibition of growth. However, compared with EGFP-transduced HUVEC, the Bcl-2-transduced cells are resistant to the apoptotic effects of serum and growth factor withdrawal and are also resistant to the induction of apoptosis by staurosporine or by ceramide, with or without TNF. Transduced Bcl-2 did not reduce TNF-mediated NF-κB activation or constitutive expression of class I MHC molecules. HUVEC expressing D34A Bcl-2 were significantly more resistant to lysis by either class I-restricted alloreactive or PHA-redirected CTL than were HUVEC expressing EGFP. We conclude that transduction of graft endothelial cells with D34A Bcl-2 is a possible approach for reducing allograft rejection.
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E-选择素在培养的人真皮微血管内皮细胞中持续表达的机制。
DOI：
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发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kluger,MS;Johnson,DR;Pober,JS
通讯作者：
Pober,JS
人肾同种异体移植物中的细胞毒性和细胞凋亡：具有细胞毒性颗粒蛋白 GMP-17 (TIA-1) 的细胞和具有碎片核 DNA 的细胞的鉴定、分布和定量。
DOI：
--
发表时间：
1997
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
Meehan,SM;McCluskey,RT;Pascual,M;Preffer,FI;Anderson,P;Schlossman,SF;Colvin,RB
通讯作者：
Colvin,RB
影响因子：
1.3
作者：
Duquesnoy,RJ;Trager,JD;Zeevi,A
通讯作者：
Zeevi,A
有证据表明，肿瘤坏死因子通过白细胞介素 1 转换酶样蛋白酶依赖性和非依赖性途径触发人内皮细胞凋亡。
DOI：
--
发表时间：
1997
期刊：
Laboratory investigation; a journal of technical methods and pathology.
影响因子：
--
作者：
Slowik,MR;Min,W;Ardito,T;Karsan,A;Kashgarian,M;Pober,JS
通讯作者：
Pober,JS
影响因子：
4.4
作者：
T. Collins;A. Krensky;C. Clayberger;W. Fiers;M. Gimbrone;S. Burakoff;J. Pober
通讯作者：
T. Collins;A. Krensky;C. Clayberger;W. Fiers;M. Gimbrone;S. Burakoff;J. Pober