CCR2 signaling contributes to ischemia-reperfusion injury in kidney

被引:203
作者
Furuichi, K
Wada, T
Iwata, Y
Kitagawa, K
Kobayashi, KI
Hashimoto, H
Ishiwata, Y
Asano, M
Wang, H
Matsushima, K
Takeya, M
Kuziel, WA
Mukaida, N
Yokoyama, H
机构
[1] Kanazawa Univ, Grad Sch Med Serv, Dept Gastroenterol & Nephrol, Kanazawa, Ishikawa 9208641, Japan
[2] Kanazawa Univ, Inst Expt Anim, Div Blood Purificat, Kanazawa, Ishikawa 9208641, Japan
[3] Kanazawa Univ, Inst Canc Res, Dept Mol Oncol, Kanazawa, Ishikawa 9208641, Japan
[4] Sanwa Kagaku Kenkyusho Co, Inabe, Japan
[5] Univ Tokyo, Grad Sch Med, Dept Mol Prevent Med, Tokyo, Japan
[6] Kumamoto Univ, Sch Med, Dept Pathol 2, Kumamoto 860, Japan
[7] Univ Texas, Sect Mol Genet & Microbiol, Austin, TX 78712 USA
[8] Univ Texas, Inst Mol & Cellular Biol, Austin, TX 78712 USA
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2003年 / 14卷 / 10期
关键词
D O I
10.1097/01.ASN.0000089563.63641.A8
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Examined were CCR2-deficient mice to clarify the contribution of macrophages via monocyte chemoattractant protein I (MCP-1 or CCL2)/CCR2 signaling to the pathogenesis of renal ischemia-reperfusion injury. Also evaluated was the therapeutic effects via the inhibition of MCP-1/CCR2 signaling with propagermanium (3-oxygermylpropionic acid polymer) and RS-504393. Renal artery and vein of the left kidney were occluded with a vascular clamp for 60 min. A large number of infiltrated cells and marked acute tubular necrosis in outer medulla after renal ischemia-reperfusion injury was observed. Ischemia-reperfusion induced the expression of MCP-1 mRNA and protein in injured kidneys, followed by CCR2-positive macrophages in interstitium in wild-type mice. The expression of MCP-1 was decreased in CCR2-deficient mice compared with wild-type mice. The number of interstitial infiltrated macrophages was markedly smaller in the CCR2-deficient mice after ischemia-reperfusion. CCR2-deficient mice decreased the number of interstitial inducible nitric oxide synthase-positive cells after ischemia-reperfusion. The area of tubular necrosis in CCR2-deficient mice was significantly lower than that of wild-type mice after ischemia-reperfusion. In addition, CCR2-deficient mice diminished KC, macrophage inflammatory protein 2, epithelial cell-derived neutrophil-activating peptide 78, and neutrophil-activating peptide 2 expression compared with wild-type mice accompanied with the reduction of interstitial granulocyte infiltration. Similarly, propagermanium and RS-504393 reduced the number of interstitial infiltrated cells and tubular necrosis up to 96 h after ischemia-reperfusion injury. These results revealed that MCP-1 via CCR2 signaling plays a key role in the pathogenesis of renal ischemia-reperfusion injury through infiltration and activation of macrophages, and it offers a therapeutic target for ischemia-reperfusion.
引用
收藏
页码:2503 / 2515
页数:13
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