Mobilization of bone marrow cells by G-CSF rescues mice from cisplatin-induced renal failure, and M-CSF enhances the effects of G-CSF

Mobilization of bone marrow cells by G-CSF rescues mice from cisplatin-induced renal failure, and M-CSF enhances the effects of G-CSF
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DOI:
10.1681/asn.2004010067
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发表时间:
2005-03-01
影响因子:
13.6
通讯作者:
Ikehara, S
Ikehara, S
中科院分区:
医学1区
文献类型:
--
作者:
Iwasaki, M;Adachi, Y;Ikehara, S

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顺铂是一种广泛使用的抗癌药物,众所周知,由于肾小管损伤而引起急性肾衰竭。本文研究了G-CSF和/或M-CSF是否能挽救顺铂诱导的肾功能衰竭小鼠。BALB/c小鼠腹腔注射G-CSF和/或M-CSF,共5d(第-5天至第-1天)。在最后一次注射G-CSF和/或M-CSF后的第二天(第0天),小鼠接受顺铂的腹膜内注射。当用G-CSF或G-CSF + M-CSF预处理时,小鼠显示出比接受M-CSF或盐水注射的小鼠更长的存活时间和更低的血清肌酐和血尿素氮水平。在组织学上,G-CSF或G-CSF + M-CSF预处理可减轻顺铂对肾小管的损伤。接受了增强型绿色荧光蛋白(EGFP)转基因小鼠骨髓细胞移植的BALB/c小鼠([EGFP-->BALB/c]小鼠)用或不用G-CSF和/或M-CSF处理,随后注射顺铂以及上述处理。用G-CSF或G-CSF + M-CSF处理的[EGFP-->BALB/c]小鼠在肾脏中显示出比仅用M-CSF或盐水处理的小鼠显著更高数量的EGFP(+)肾小管上皮细胞。提示G-CSF动员的骨髓细胞可促进肾功能的改善,预防顺铂所致的肾小管损伤,而M-CSF可增强G-CSF的作用。
Cisplatin, which is a broadly used anticancer drug, is widely known to induce acute renal failure as a result of renal tubular injury. This article examines whether G-CSF and/or M-CSF rescues mice from renal failure induced by cisplatin. BALB/c mice received intraperitoneal injections with or without G-CSF and/or M-CSF for 5 d (from day -5 to day -1). The day after the last injection of G-CSF and/or M-CSF (day 0), the mice received an intraperitoneal injection of cisplatin. When pretreated with G-CSF or G-CSF + M-CSF, the mice showed longer survival and lower serum creatinine and blood urea nitrogen levels than mice that had been received injections of M-CSF or saline. Histologically, pretreatment with G-CSF or G-CSF + M-CSF attenuated the damage to renal tubules induced by cisplatin. BALB/c mice that had received a transplant of bone marrow cells of enhanced green fluorescent protein (EGFP)-transgenic mice ([EGFP-->BALB/c] mice) were treated with or without G-CSF and/or M-CSF, followed by injection of cisplatin as well as above. [EGFP-->BALB/c] mice that were treated with G-CSF or G-CSF + M-CSF showed a significantly higher number of EGFP(+) tubular epithelial cells in the kidney than mice that were treated with only M-CSF or saline. These results suggest that bone marrow cells mobilized by G-CSF accelerate the improvement in renal functions and prevent the renal tubular injury induced by cisplatin and that M-CSF enhances the effects of G-CSF.