The E-Selectin Ligand Basigin/CD147 Is Responsible for Neutrophil Recruitment in Renal Ischemia/Reperfusion
The E-Selectin Ligand Basigin/CD147 Is Responsible for Neutrophil Recruitment in Renal Ischemia/Reperfusion
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DOI：
10.1681/asn.2008090957
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发表时间：
2009-07-01
影响因子：
13.6
通讯作者：
Kadomatsu, Kenji
中科院分区：
文献类型：
--
作者：
Kato, Noritoshi;Yuzawa, Yukio;Kadomatsu, Kenji
E-选择素及其配体对于炎症中白细胞的外渗是必不可少的。在此，我们报道Basigin(BSG)/CD147是E-选择素的配体，促进缺血/再灌流时的肾脏炎症。与野生型小鼠相比，BSG缺陷(-/-)小鼠在肾缺血/再灌流后可显著抑制中性粒细胞在肾脏的浸润。尽管E-选择素在两种基因型鼠之间的表达增加相似，但BSG(-/-)小鼠的肾脏损伤较少，这表明BSG对中性粒细胞的影响在该模型中起到了促进肾损伤的作用。BSG(-/-)中性粒细胞与E-选择素的结合减少。从与E-选择素结合的HL-60细胞中分离出的BSG和衣霉素处理取消了这种结合。此外，BSG(-/-)中性粒细胞在体外对人脐静脉内皮细胞的E-选择素依赖性黏附减少。将标记的中性粒细胞注射到小鼠体内表明，无论受体的基因如何，BSG(-/-)中性粒细胞在肾缺血/再灌注后较BSG(+/+)中性粒细胞更不容易被招募到肾脏。综上所述，BSG是E-选择素的生理性配体，在肾缺血/再灌流损伤中起重要作用。
E-selectin and its ligands are essential for extravasation of leukocytes in inflammation. Here, we report that basigin (Bsg)/CD147 is a ligand for E-selectin that promotes renal inflammation in ischemia/reperfusion. Compared with wild-type mice, Bsg-deficient (Bsg(-/-)) mice demonstrated striking suppression of neutrophil infiltration in the kidney after renal ischemia/reperfusion. Although E-selectin expression increased similarly between the two genotypes, Bsg(-/-) mice exhibited less renal damage, suggesting that Bsg on neutrophils contribute to renal injury in this model. Neutrophils expressed Bsg with Winked polylactosamine chains and Bsg(-/-) neutrophils showed reduced binding to E-selectin. Bsg isolated from HL-60 cells bound to E-selectin, and tunicamycin treatment to abolish Winked glycans from Bsg abrogated this binding. Furthermore, Bsg(-/-) neutrophils exhibited reduced E-selectin-dependent adherence to human umbilical vein endothelial cells in vitro. Injection of labeled neutrophils into mice showed that Bsg(-/-) neutrophils were less readily recruited to the kidney after renal ischemia/reperfusion than Bsg(+/+) neutrophils, regardless of the recipient's genotype. Taken together, these results indicate that Bsg is a physiologic ligand for E-selectin that plays a critical role in the renal damage induced by ischemia/reperfusion.