Human hepatocytes produce an isoform of FAS that inhibits apoptosis.

Human hepatocytes produce an isoform of FAS that inhibits apoptosis.
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人类肝细胞产生一种抑制细胞凋亡的 FAS 亚型。

DOI:
10.1097/00007890-199803150-00019
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发表时间:
1998
期刊:
影响因子:
6.2
通讯作者:
Martinez,OM
Martinez,OM
中科院分区:
医学2区
文献类型:
--
作者:
Krams,SM;Fox,CK;Beatty,PR;Cao,S;Villanueva,JC;Esquivel,CO;Martinez,OM

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Fas(Apo-1/CD 95)是肿瘤坏死因子受体家族成员之一,当与其配体或抗Fas抗体结合时,可介导细胞凋亡。Fas由免疫系统细胞和一些非淋巴组织表达。大量研究表明Fas信号通路可能在同种异体移植排斥反应中发挥作用。Fas受体的功能性可溶形式由活化的外周血单核细胞和一些转化的细胞系产生。本研究的目的是确定是否可溶性变体的Fas在肝脏中产生,并确定是否封锁的Fas通路,由肝脏衍生的可溶性Fas,抑制Fas介导的apoptosis.Methods.肝脏和纯化的肝细胞标本进行了分析Fas转录物的逆转录-聚合酶链反应与引物,跨越跨膜区的分子。通过特异性酶联免疫吸附试验分析胆汁和细胞裂解物中的可溶性Fas。从正常肝脏和肝细胞制备裂解物,并利用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记和流式细胞术检测阻断Fas介导的Jurkat细胞凋亡。Fas的这种变体形式在所有正常肝脏标本中表达,但仅在移植排斥反应期间获得的一半肝脏标本中表达。与移植物稳定的患者相比,接受肝移植排斥反应的患者可溶性Fas水平降低。重要的是,可溶性形式的Fas是在肝脏中产生的肝细胞,可以特异性地抑制Fas介导的apoptosis.Conclusion.These data raised the possibility that soluble Fas,由肝细胞产生,可能会影响免疫反应,通过阻断Fas介导的细胞凋亡,因此,可能有一个作用,在肝移植。
Background.Fas (Apo-1/CD95), a member of the tumor necrosis factor receptor family, can mediate apoptosis when engaged by its ligand or by anti-Fas anti-body. Fas is expressed by cells of the immune system and by some nonlymphoid tissues. Numerous studies have suggested that the Fas pathway may play a role in the rejection of allografts. Functional, soluble forms of the Fas receptor are produced by activated peripheral blood mononuclear cells and some transformed cell lines. The purpose of this study was to determine if soluble variants of Fas are produced in the liver and to determine if blockade of the Fas pathway, by liver-derived soluble Fas, inhibits Fas-mediated apoptosis.Methods.Liver and purified hepatocyte specimens were analyzed for Fas transcripts by reverse transcriptase-polymerase chain reaction with primers that span the transmembrane region of the molecule. Bile and cell lysates were analyzed for soluble Fas by specific enzyme-linked immunosorbent assay. Lysates were prepared from normal liver and hepatocytes and utilized to block Fas-mediated apoptosis of Jurkat cells as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and flow cytometry.Results.A variant form of Fas is abundantly expressed in normal liver and purified hepatocytes. This variant form of Fas is expressed in all normal liver specimens but only in half of the liver specimens obtained during allograft rejection. The levels of soluble Fas diminish in patients undergoing liver allograft rejection in contrast to patients with stable grafts. Importantly, a soluble form of Fas is produced in the liver by hepatocytes and can specifically inhibit Fas-mediated apoptosis.Conclusion.These data raise the possibility that soluble Fas, produced by hepatocytes, may influence the immune response by blocking Fas-mediated apoptosis and, thus, may have a role in liver transplantation.
DOI: 10.1097/00007890-199401001-00002
发表时间: 1994-01-01
期刊: TRANSPLANTATION
影响因子: 6.2
作者:
FARGES, O;MORRIS, PJ;DALLMAN, MJ
通讯作者: DALLMAN, MJ
DOI: 10.1097/00007890-199508000-00002
发表时间: 1995
期刊: Transplantation
影响因子: 6.2
作者:
Larsen,CP;Alexander,DZ;Hendrix,R;Ritchie,SC;Pearson,TC
通讯作者: Pearson,TC
血清可溶性 Fas/APO-1 水平与自身免疫性疾病之间缺乏相关性。
DOI: 10.1002/art.1780381206
发表时间: 1995
影响因子: --
作者:
Goel,N;Ulrich,DT;StClair,EW;Fleming,JA;Lynch,DH;Seldin,MF
通讯作者: Seldin,MF
在小肠移植实验模型中,CD8 细胞对于同种异体移植排斥或诱导细胞凋亡不是必需的。
DOI: --
发表时间: 1998
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Krams,SM;Hayashi,M;Fox,CK;Villanueva,JC;Whitmer,KJ;Burns,W;Esquivel,CO;Martinez,OM
通讯作者: Martinez,OM
DOI: 10.4049/jimmunol.148.4.1274
发表时间: 1992-02
影响因子: 4.4
作者:
Rie Watanabe‐Fukunaga;C. Brannan;N. Itoh;S. Yonehara;N. Copeland;N. Jenkins;S. Nagata
通讯作者: Rie Watanabe‐Fukunaga;C. Brannan;N. Itoh;S. Yonehara;N. Copeland;N. Jenkins;S. Nagata