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The Regulation of DC Apoptosis by Bax and Bcl-2

Bax和Bcl-2对DC细胞凋亡的调控

基本信息

批准号：
7091589
负责人：
HECTOR SANDOVAL
金额：
$ 3.22万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-01 至 2007-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Dendritic cells (DC) are the professional antigen presenting cells that process and present antigens to lymphocytes [1]. It was demonstrated that DC migrate to the lymph node to activate naive T cells and are eliminated by antigen-specific T cells within 48 hours of arriving at the lymph node [3]. This T cell directed DC elimination led to yet another mechanism of regulating the immune system through DC apoptosis [4]. DC apoptosis occurs by either cytokine deprivation or by antigen-specific T lymphocytes [4, 5]. DC can be killed by T cells through Fas or perforin and granzyme B [4, 6]. Furthermore, deprivation of the cytokine GM-CSF from DC induces the down-regulation of an antiapoptotic protein Bcl-2 that results in the disruption of the mitochondrial membrane [7]. It was also demonstrated that over-expression of the anti-apoptotic Bcl-2 increases the lifespan of DC in vivo [8]. The disruption of mitochondrion plays an important role in regulating apoptosis induced by cytokine deprivation, granzyme B, and Fas signaling [9-11]. The regulation of the mitochondrial membrane integrity is controlled by the ratio of the pro and anti-apoptotic BCL-2 family members [2]. Because Bcl-2 and Bax play important roles in regulating the integrity of mitochondrion membrane, I hypothesize that Bax and Bcl-2 are important regulators of DC apoptosis.

描述（申请人提供）：树突状细胞（DC）是专职抗原呈递细胞，可加工抗原并将抗原呈递给淋巴细胞[1]。已证明DC迁移至淋巴结以激活初始T细胞，并在到达淋巴结的48小时内被抗原特异性T细胞消除[3]。这种T细胞定向的DC消除导致通过DC凋亡调节免疫系统的另一种机制[4]。DC凋亡通过细胞因子剥夺或抗原特异性T淋巴细胞发生[4，5]。DC可被T细胞通过Fas或穿孔素和颗粒酶B杀死[4，6]。此外，从DC中去除细胞因子GM-CSF诱导抗凋亡蛋白Bcl-2的下调，导致线粒体膜的破坏[7]。还证明抗凋亡Bcl-2的过表达增加了体内DC的寿命[8]。细胞因子的破坏在调节细胞因子剥夺、颗粒酶B和Fas信号传导诱导的细胞凋亡中起重要作用[9-11]。线粒体膜完整性的调节由促凋亡和抗凋亡BCL-2家族成员的比例控制[2]。由于Bcl-2和Bax在调节树突状细胞膜的完整性中起重要作用，因此我推测Bax和Bcl-2是DC凋亡的重要调节因子。