Chou S C, Flood P M, Raleigh J A
Department of Radiation Oncology, University of North Carolina, Chapel Hill 27599, USA.
Br J Cancer Suppl. 1996 Jul;27:S213-6.
Artificial antigens are created when 2-nitroimidazoles bind to hypoxic cells. These antigens have been used in the immunodetection of tumour hypoxia but they might also serve to stimulate immune lysis of hypoxic tumour cells by complement- and cell-mediated processes. In order to test this hypothesis, lymphocytes isolated from the spleens of C3H/HeN mice that had been immunised with pimonidazole-labelled 3152-PRO cells were subcultured and tested for their ability to lyse chromium-51 loaded, pimonidazole-labelled 3152-PRO cells in an in vitro assay. In a parallel study, commercially available, rabbit complement was tested for its ability to lyse pimonidazole-labelled V79-4 cells in the presence of monoclonal antibodies which recognise protein adducts of reductively activated pimonidazole. Complement-mediated cell lysis was measured by means of an MTT assay. Complement-mediated and cell-mediated lysis was observed at pimonidazole concentrations which, in themselves, do not produce cell killing.
当2-硝基咪唑与缺氧细胞结合时,人工抗原就会产生。这些抗原已被用于肿瘤缺氧的免疫检测,但它们也可能通过补体和细胞介导的过程刺激缺氧肿瘤细胞的免疫裂解。为了验证这一假设,从用匹莫硝唑标记的3152-PRO细胞免疫的C3H/HeN小鼠脾脏中分离出淋巴细胞,进行传代培养,并在体外试验中检测它们裂解负载有铬-51、用匹莫硝唑标记的3152-PRO细胞的能力。在一项平行研究中,检测了市售兔补体在识别还原激活的匹莫硝唑蛋白加合物的单克隆抗体存在下裂解用匹莫硝唑标记的V79-4细胞的能力。通过MTT测定法测量补体介导的细胞裂解。在匹莫硝唑浓度本身不会导致细胞杀伤的情况下,观察到了补体介导的和细胞介导的裂解。