Apoptosis of Neutrophils in Uremia

描述：(申请人提供)：在美国，感染是主要原因 慢性肾功能衰竭(CRF)患者的死亡率。这在一定程度上是由于 到了免疫缺陷的尿毒症综合征。在过去的十年里，细胞凋亡或程序性细胞死亡(PCD)一直是人们密切关注的主题。 与坏死不同，细胞凋亡是一种程序性的、主动的和高度选择性的 死亡机制，允许移除多余的或过度损坏的 细胞。它是发育和细胞调节的重要组成部分，而且 在过量和减量的情况下，具有病理生理和治疗作用 这意味着什么。在CRF中，多形核白细胞(PMN)经历加速 PCD。这项提案的长期目标是阐明细胞和 慢性肾功能衰竭中性粒细胞凋亡的分子机制。这些研究将 特别关注三个主要的信号通路：Fas/FasL 系统、Bax/BC12系统和氧化应激。这些研究将利用PMN (健康人和CRF患者)和HL-60粒细胞。细胞凋亡 诱导模型将使用受体和应激介导的刺激(抗Fas 抗体、抗氧化剂、透析膜、尿毒症毒素等)。这个 这些结果有望增强我们对慢性肾功能衰竭患者白细胞生物学的理解， 并为开发对抗免疫的新策略奠定了基础 慢性肾功能衰竭的功能障碍。

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.