Department of Laboratory Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
Nephrology (Carlton). 2011 Aug;16(6):545-51. doi: 10.1111/j.1440-1797.2011.01473.x.
A recent report showed that fractalkine (CX3CL1), which functions as both a potent chemoattractant and adhesion molecule for monocytes and natural killer (NK) cells was significantly increased in cisplatin-induced acute renal failure (CisARF) in mice. Therefore, we developed the hypothesis that increased CX3CL1 expression in CisARF initiates NK cell infiltration in the kidney. The aim of the present study was to determine the role of NK cells in CisARF in mice.
Time course of pan-NK positive cells in CisARF was investigated by using immunohistochemistry (IHC) for CD49b. Pan-NK positive cells were reduced by using anti-NK1.1 mAb. The model of pan-NK positive cells reduction was confirmed by flow cytometry of the spleen and IHC of the kidney. The expression of granzyme A and caspase-1 was examined, and the activity of caspase-1 was also determined. We performed a study on whether there was significant protection of renal function after reduction of pan-NK positive cells.
(i) Infiltration of pan-NK positive cells was prominent on day 3 after cisplatin administration. (ii) granzyme A expression was significantly increased in CisARF and CisARF+NK1.1 Ab compared to vehicle. (iii) Caspase-1 expression and activity was significantly increased in CisARF mice compared to vehicle and CisARF+NK1.1 Ab. (iv) Reduction of pan-NK positive cells was not protective in cisplatin-induced acute renal failure in mice.
Although infiltration of pan-NK cells was significantly increased in CisARF, reduction of infiltration of pan-NK cells into the kidney was not protective against CisARF in mice.
最近的一份报告显示，趋化因子（CX3CL1）作为单核细胞和自然杀伤（NK）细胞的有效趋化因子和黏附分子，在顺铂诱导的急性肾衰竭（CisARF）小鼠中显著增加。因此，我们提出假设，CisARF 中 CX3CL1 表达的增加引发 NK 细胞浸润肾脏。本研究旨在确定 NK 细胞在 CisARF 小鼠中的作用。
通过免疫组织化学（IHC）检测 CD49b 来研究 CisARF 中 pan-NK 阳性细胞的时间进程。使用抗 NK1.1 mAb 减少 pan-NK 阳性细胞。通过脾的流式细胞术和肾的 IHC 确认 pan-NK 阳性细胞减少模型。检查颗粒酶 A 和半胱天冬酶-1 的表达，并测定半胱天冬酶-1 的活性。我们研究了减少 pan-NK 阳性细胞后肾功能是否有显著保护作用。
（i）顺铂给药后第 3 天，pan-NK 阳性细胞浸润明显。（ii）与载体相比，CisARF 和 CisARF+NK1.1 Ab 中颗粒酶 A 表达显著增加。（iii）与载体和 CisARF+NK1.1 Ab 相比，CisARF 小鼠中半胱天冬酶-1 表达和活性显著增加。（iv）减少 pan-NK 阳性细胞对 CisARF 小鼠的顺铂诱导急性肾衰竭没有保护作用。
尽管 CisARF 中 pan-NK 细胞浸润明显增加，但减少 pan-NK 细胞浸润肾脏对 CisARF 小鼠没有保护作用。
