Apoptosis of Neutrophils in Uremia

尿毒症中性粒细胞凋亡

• 批准号: 6794582
• 负责人: MARY C PERIANAYAGAM
• 金额: $ 5.65万
• 依托单位: STEWARD ST. ELIZABETH'S MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6794582
• 关键词: Bax gene /protein; CD95 molecule; antireceptor antibody; apoptosis; biological signal transduction; cellular pathology; chronic renal failure; clinical research; granulocyte; human subject; neutrophil; oxidative stress; oxidizing agents; postdoctoral investigator; renal toxin; uremias

DESCRIPTION: (provided by applicant): In the U.S., infection is a leading cause of death among patients with chronic renal failure (CRF). This is due in part to the immune deficiency of the uremic syndrome. In the past decade, apoptosis or programmed cell death (PCD) has been the subject of intense investigation. In contrast to necrosis, apoptosis is a programmed, active and highly selective death mechanism, allowing for the removal of redundant or excessively damaged cells. It is an essential component of development and cellular regulation, and in both excessive and reduced amount, has pathophysiological and therapeutic implications. In CRF, polymorphonuclear leukocytes (PMN) undergo accelerated PCD. The long-term goals of this proposal are to elucidate the cellular and molecular pathways governing PMN apoptosis in CRF. The studies will specifically concentrate on three major signaling pathways: the Fas/FasL system, the Bax/Bc12 system and oxidative stress. The studies will utilize PMN (healthy subjects and patients with CRF) and HL-60 granulocytes. Apoptosis induction models will use receptor- and stress-mediated stimuli (anti-Fas antibodies, pro-oxidant agents, dialysis membranes, uremic toxins, etc). The results are expected to enhance our understanding of leukocyte biology in CRF, and lay the foundation for developing novel strategies to combat immune dysfunction in CRF.

描述：（申请人提供）：在美国，感染是主要原因 慢性肾衰竭（CRF）患者的死亡。这部分应 尿毒综合征的免疫缺乏。在过去的十年中，细胞凋亡或程序性细胞死亡（PCD）一直是严格研究的主题。 与坏死相反，凋亡是一种编程，活跃且高度选择性的 死亡机制，允许去除多余或过度损坏 细胞。它是发育和细胞调节的重要组成部分， 在过多和减少的量中，具有病理生理和治疗性 含义。在CRF中，多形核白细胞（PMN）经历了加速 PCD。该提议的长期目标是阐明细胞和 控制CRF中PMN凋亡的分子途径。研究会 专门集中于三个主要信号通路：FAS/FASL 系统，BAX/BC12系统和氧化应激。研究将利用PMN （健康受试者和CRF患者）和HL-60粒细胞。凋亡 诱导模型将使用受体和应力介导的刺激（抗FAS） 抗体，促氧化剂，透析膜，尿毒症毒素等）。这 预计结果将增强我们对CRF中白细胞生物学的理解， 并为制定新型策略打击免疫力而奠定基础 CRF功能障碍。