Mobilization of bone marrow cells by G-CSF rescues mice from cisplatin-induced renal failure, and M-CSF enhances the effects of G-CSF.
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.
Iwasaki
Masayoshi
M
First Department of Pathology, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
Adachi
Yasushi
Y
Minamino
Keizo
K
Suzuki
Yasuhiro
Y
Zhang
Yuming
Y
Okigaki
Mitsuhiko
M
Nakano
Keiji
K
Koike
Yasushi
Y
Wang
Jianfeng
J
Mukaide
Hiromi
H
Taketani
Shigeru
S
Mori
Yasukiyo
Y
Takahashi
Hakuo
H
Iwasaka
Toshiji
T
Ikehara
Susumu
S
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D002945:Cisplatin / Q000633:toxicity; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D019650:Hematopoietic Stem Cell Mobilization; D007668:Kidney / Q000473:pathology / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic
D000970:Antineoplastic Agents; D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins; D016173:Macrophage Colony-Stimulating Factor; D002945:Cisplatin