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

• Published in: Journal of the American Society of Nephrology 2005-03, Vol.16 (3), p.658-666
• Main Authors: IWASAKI, Masayoshi, ADACHI, Yasushi, TAKETANI, Shigeru, MORI, Yasukiyo, TAKAHASHI, Hakuo, IWASAKA, Toshiji, IKEHARA, Susumu, MINAMINO, Keizo, SUZUKI, Yasuhiro, YUMING ZHANG, OKIGAKI, Mitsuhiko, NAKANO, Keiji, KOIKE, Yasushi, JIANFENG WANG, MUKAIDE, Hiromi
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - drug therapy; Acute Kidney Injury - mortality; Animals; Antineoplastic Agents - toxicity; Biological and medical sciences; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - radiation effects; Bone Marrow Transplantation; Cisplatin - toxicity; Drug Synergism; Drug toxicity and drugs side effects treatment; Granulocyte Colony-Stimulating Factor - pharmacology; Green Fluorescent Proteins - genetics; Hematopoietic Stem Cell Mobilization; Kidney - pathology; Kidney - physiology; Macrophage Colony-Stimulating Factor - pharmacology; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Transgenic; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Pharmacology. Drug treatments; Renal failure; Toxicity: urogenital system
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2004010067

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.