Department of Radiology, 1695A Eastchester Road, Albert Einstein College of Medicine, Bronx, NY, USA.
Future Microbiol. 2013 Sep;8(9):1081-9. doi: 10.2217/fmb.13.79.
Previously, we showed that radioimmunotherapy (RIT) for cryptococcal infections using radioactively labeled antibodies recognizing the cryptococcal capsule reduced fungal burden and prolonged survival of mice infected with Cryptococcus neoformans. Here, we investigate the effects of RIT on bystander mammalian cells.
MATERIALS & METHODS: Heat-killed C. neoformans bound to anticapsular antibodies, unlabeled or labeled with the β-emitter rhenium-188 (16.9-h half-life) or the α-emitter bismuth-213 (46-min half-life), was incubated with macrophage-like J774.16 cells or epithelial-like Chinese hamster ovary cells. Lactate dehydrogenase activity, crystal violet uptake, reduction of tetrazolium dye (2,3)-bis-(2-methoxy-4-nitro-5-sulfenyl)-(2H)-terazolium-5-carboxanilide and nitric oxide production were measured.
The J774.16 and Chinese hamster ovary cells maintained membrane integrity, viability and metabolic activity following exposure to radiolabeled C. neoformans.
RIT of C. neoformans is a selective therapy with minimal effects on host cells and these results are consistent with observations that RIT-treated mice with cryptococcal infection lacked RIT-related pathological changes in lungs and brain tissues.
此前,我们已经表明,使用放射性标记的抗体识别隐球菌荚膜对隐球菌感染进行放射性免疫治疗(RIT)可降低真菌负荷并延长新型隐球菌感染小鼠的存活时间。在这里,我们研究 RIT 对旁观者哺乳动物细胞的影响。
热灭活的新型隐球菌与抗荚膜抗体结合,未标记或用β发射体铼-188(半衰期 16.9 小时)或α发射体铋-213(半衰期 46 分钟)标记,与巨噬细胞样 J774.16 细胞或上皮样中国仓鼠卵巢细胞孵育。测量乳酸脱氢酶活性、结晶紫摄取、四唑染料(2,3)-双-(2-甲氧基-4-硝基-5-亚磺酰基)-(2H)-噻唑-5-羧酰胺和一氧化氮的产生。
暴露于放射性标记的新型隐球菌后,J774.16 和中国仓鼠卵巢细胞保持了膜完整性、活力和代谢活性。
新型隐球菌的 RIT 是一种选择性治疗方法,对宿主细胞的影响很小,这些结果与 RIT 治疗的隐球菌感染小鼠在肺部和脑组织中缺乏与 RIT 相关的病理变化的观察结果一致。