ROLE OF NK CYTOTOXIC FACTOR NKCF IN NK CYTOTOXICITY

NK 细胞毒性因子 NKCF 在 NK 细胞毒性中的作用

• 批准号: 3173362
• 负责人: BENJAMIN BONAVIDA
• 金额: $ 13.64万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1989-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3173362
• 关键词: antibody formation; gel electrophoresis; high performance liquid chromatography; immunochemistry; immunotoxicity; laboratory mouse; laboratory rat; leukocyte activation /transformation; monoclonal antibody; neoplasm /cancer immunology; protein structure; tissue /cell culture

Previous studies of the natural killer (NK) lytic mechanism have provided evidence for the stimulus secretion model and led to the postulation that lytic mediators are transferred from the effector to the target cell. Subsequent work in our laboratory has demonstrated that soluble natural killer cytotoxic factors (NKCF) can be detected in the supernatant of effector cells stimulated with NK targets. These factors are NK specific and lyse only NK sensitive targets. Further studies have shown that NKCF conform with known characteristics of the NK CMC reaction and we have postulated that NKCF plays a role in NK CMC cytotoxicity function. The following model for NK CMC was then proposed by which, following effector target cell binding, the target stimulates the effector to release NKCF. These factors then bind to and lyse the target cells. Preliminary studies have shown that NKCF are glycoproteins and can be fractionated on HPLC gel-filtration into cytotoxic fractions of molecular weight 20-30 kilodaltons. Furthermore, we have been able to generate xeno and monoclonal antibodies that can inhibit NK CMC sctivity and in a few instances neutralize NKCF activity. In the proposal we plan to: 1) further characterize and biochemically purify NKCF to homogeneity, 2) characterize antibodies (poly or monoclonal) specific for NKCF, and examine their role in NK CMC reactions, and 3) in collaboration with other investigators, compare NKCF with recently described cytolytic granules or cytotoxins and lymphotoxins derived from NK and CTL lines. We will use conventional methods of protein purification and structure analysis. Conventional and monoclonal antibodies will be generated against NKCF and will be characterized for their role in blocking NK CMC reactions. The studies proposed are significant and unique in the field of CMC. They are also clinically important since they describe naturally derived antitumor cytolytic molecules that may be relevant in immunotherapy. (LB)

以往对自然杀伤（NK）的裂解机制的研究提供了

项目成果

Studies on the mechanism of natural killer cell-mediated cytotoxicity. VII. functional comparison of human natural killer cytotoxic factors with recombinant lymphotoxin and tumor necrosis factor.

自然杀伤细胞介导的细胞毒作用机制的研究。

• 发表时间: 1987
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Wright,SC;Bonavida,B
• 通讯作者: Bonavida,B

Effect of altered membrane structure on NK cell-mediated cytotoxicity. II. Conversion of NK-resistant tumor cells into NK-sensitive targets upon fusion with liposomes containing NK-sensitive membranes.

膜结构改变对 NK 细胞介导的细胞毒性的影响。

• 发表时间: 1986
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Roozemond,RC;vanderGeer,P;Bonavida,B
• 通讯作者: Bonavida,B

Liposomes can function as targets for natural killer cytotoxic factor but not for tumor necrosis factor.

脂质体可以作为自然杀伤细胞毒性因子的靶标，但不能作为肿瘤坏死因子的靶标。

• 发表时间: 1989
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Roozemond,RC;Urli,DC;Jansen,J;Bonavida,B
• 通讯作者: Bonavida,B

Lysis of natural killer-sensitive and -resistant tumor cells by natural killer cytotoxic factors (NKCF)-containing liposomes.

通过含有自然杀伤细胞毒性因子 (NKCF) 的脂质体裂解自然杀伤敏感和耐药的肿瘤细胞。

• DOI: 10.1016/s0171-2985(87)80098-0
• 发表时间: 1987
• 期刊: Immunobiology
• 影响因子: 2.8
• 作者: Roozemond,RC;Urli,DC;Wright,SC;Graves,SS;Bonavida,B
• 通讯作者: Bonavida,B

Both NK sensitive and resistant mycoplasma free cell lines stimulate release of NKCF.

NK 敏感和耐药的无支原体细胞系都会刺激 NKCF 的释放。

• DOI: 10.1007/978-1-4684-8326-0_13
• 发表时间: 1985
• 期刊: Advances in experimental medicine and biology
• 作者: Wright,SC;Bonavida,B
• 通讯作者: Bonavida,B