REGULATION OF APOPTOSIS BY NOS

描述（改编自研究者摘要）：一氧化氮（NO） 是一种小的、高活性的气体，由NO合酶（NOS）合成。 小鼠白细胞中的NOS活性已被证明在细胞凋亡中起重要作用。 在小鼠免疫反应中。 然而，NOS在人体免疫系统中的作用 系统仍然是高度有争议的，因为NOS相关的影响，在人类 白细胞很难证明。 我们的初步数据 表明在人体中组成型表达NOS水平非常低 淋巴细胞或单核细胞衍生的细胞系调节细胞凋亡。 我们 假设NOS活性调节人原发性肝癌细胞凋亡 淋巴细胞和/或单核细胞以及细胞系中，因此， NOS活性在人体免疫系统中具有生理相关作用。 在具体目标1中，我们将通过确定是否 人原代淋巴细胞和单核细胞中的NOS活性调节 自发或Fas诱导凋亡。 在特异性目标2中，人淋巴细胞 细胞系将被用作模型来研究NOS 抑制Fas诱导的凋亡。 我们的假设是NOS活性 在Fas相关蛋白水平抑制Fas诱导的细胞凋亡 复杂的形成。 这些研究将有助于免疫学 和一氧化氮场 这些研究将阐明NOS活性是否 在人类和小鼠免疫系统中的生理作用： 提供了深入了解NOS活性发挥生物学作用的机制， 在人类细胞中的作用;并将阐明一种新的NOS依赖性调节 Fas诱导的凋亡。 最终，这些研究可能会导致 开发基于NO的疗法来治疗与以下疾病相关的疾病 细胞凋亡的失调，包括自身免疫性疾病、癌症和 获得性免疫缺陷综合症

DESCRIPTION (Adapted from the Investigator's abstract): Nitric oxide (NO) is a small, highly reactive gas synthesized by the enzyme NO synthase (NOS). NOS activity in murine leukocytes has been shown to play an important role in the murine immune response. However, the role of NOS in the human immune system remains highly controversial because NOS-associated effects in human leukocytes have been very difficult to demonstrate. Our preliminary data indicate that very low levels of NOS expressed constitutively in human lymphocyte or monocyte-derived cells lines regulate apoptosis. We hypothesize that NOS activity regulates apoptosis in human primary lymphocytes and/or monocytes as well as in cell lines, and therefore, that NOS activity has a physiologically relevant role in the human immune system. In Specific Aim 1, we will test this hypothesis by determining if NOS-activity in human primary lymphocytes and monocytes regulates spontaneous or Fas-induce apoptosis. In Specific Aim 2, human lymphocytic cell lines will be used as models to investigate the mechanism by which NOS inhibits Fas-induced apoptosis. Our hypothesis is that NOS activity inhibits Fas-induced apoptosis at the level of Fas-associated protein complex formation. The proposed studies will contribute ot the immunology and nitric oxide fields. The studies will clarify whether NOS activity has a physiologic role in the human as well as the murine immune system: will provide insight into the mechanism by which NOS activity exerts biological effects in human cells; and will elucidate a novel NOS-dependent regulation of Fas-induced apoptosis. Ultimately these studies may lead to the development of NO-based therapies to treat disorders associated with dysregulation of apoptosis including autoimmune diseases, cancer and the acquired immunodeficiency syndrome.