TARGET CELL INDUCED ELEVATION OF CAMP IN NK CELLS

靶细胞诱导 NK 细胞中 CAMP 的升高

• 批准号: 6027556
• 负责人: MARGARET M WHALEN
• 金额: $ 9.45万
• 依托单位: TENNESSEE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6027556
• 关键词: G protein; MHC class I antigen; adenylate cyclase; biological signal transduction; cell cell interaction; cyclic AMP; cytotoxicity; enzyme activity; human subject; leukocyte activation /transformation; natural killer cells; phosphodiesterases; protein biosynthesis; receptor; receptor binding; tissue /cell culture

DESCRIPTION (Adapted from the Investigator's Abstract): The binding of NK cells to lysis-sensitive (LS) target cells initiates a series of biochemical responses. Although most of the initiated pathways appear to participate during NK cell effector function, the induction of elevated cAMP levels may elicit a feedback regulatory system. This proposal seeks to further define how LS-target cell binding induces increased cellular accumulation of cAMP, and how this impacts upon NK cell effector capabilities. This proposal is divided into four specific aims, with the first three committed to understanding the mechanisms involved with elevating cAMP levels. The first aim will characterize the relative contributions of increased adenylyl cyclase (AC) and decreased phosphodiesterase (PDE) activities to this increase. The second aim will determine how receptor occupancy regulates AC activity. The third aim is to identify which PDE isoforms are operative in NK cells and how their activities are regulated after engagement of LS-targets. The fourth aim will initiate the characterization of how elevated cAMP levels impact on the cytolytic capabilities of NK cells.

描述（改编自研究者摘要）：NK的结合 细胞与裂解敏感（LS）靶细胞的结合引发一系列生物化学反应， 应答 虽然大多数启动的途径似乎参与了 在NK细胞效应功能期间，cAMP水平升高的诱导可能 引出反馈调节系统。 该提案旨在进一步界定 LS-靶细胞结合如何诱导cAMP的细胞积累增加， 以及这如何影响NK细胞效应子的能力。 这项建议是 分为四个具体目标，前三个目标致力于 了解cAMP水平升高的机制。 第一 目的是描述腺苷酸增加的相对贡献， 环化酶（AC）和磷酸二酯酶（PDE）活性降低， 增加 第二个目标将确定受体占据如何调节AC 活动 第三个目的是确定哪些PDE亚型在 NK细胞及其活动在参与后如何受到调节 LS-目标。 第四个目标将开始描述如何 升高的cAMP水平影响NK细胞的细胞溶解能力。

项目成果

Interleukins 2 and 12 produce recovery of cytotoxic function in tributyltin-exposed human natural killer cells.

白细胞介素 2 和 12 可恢复暴露于三丁基锡的人类自然杀伤细胞的细胞毒性功能。

• DOI: 10.1006/enrs.2002.4332
• 发表时间: 2002
• 期刊: Environmental research
• 影响因子: 8.3
• 作者: Whalen,MargaretM;Williams,TarrahB;Green,StephanieA;Loganathan,BommannaG
• 通讯作者: Loganathan,BommannaG

Interleukins 2 and 12 produce significant recovery of cytotoxic function in dibutyltin-exposed human natural killer cells.

白细胞介素 2 和 12 可使暴露于二丁基锡的人类自然杀伤细胞的细胞毒性功能显着恢复。

• DOI: 10.1006/enrs.2001.4323
• 发表时间: 2002
• 期刊: Environmental research.
• 作者: Whalen,MargaretM;Walker,Latarchal;Loganathan,BommannaG
• 通讯作者: Loganathan,BommannaG

Brief exposure to triphenyltin produces irreversible inhibition of the cytotoxic function of human natural killer cells.

短暂接触三苯基锡会对人类自然杀伤细胞的细胞毒功能产生不可逆的抑制。

• DOI: 10.1016/s0013-9351(03)00043-4
• 发表时间: 2003
• 期刊: Environmental research
• 影响因子: 8.3
• 作者: Whalen,MargaretM;Wilson,Sharnise;Gleghorn,Carrnes;Loganathan,BommannaG
• 通讯作者: Loganathan,BommannaG

Butyltin exposure causes a rapid decrease in cyclic AMP levels in human lymphocytes.

• DOI: 10.1006/taap.2000.9121
• 发表时间: 2001-03
• 期刊: Toxicology and applied pharmacology
• 影响因子: 3.8
• 作者: M. Whalen;B. Loganathan