Received September 12, 2008
Accepted on February 27, 2009

BASIC RESEARCH

The E-Selectin Ligand Basigin/CD147 Is Responsible for Neutrophil Recruitment in Renal Ischemia/Reperfusion

Noritoshi Kato ^*, Yukio Yuzawa , Tomoki Kosugi ^*, Akinori Hobo ^*, Waichi Sato , Yuko Miwa ^*, Kazuma Sakamoto ^*, Seiichi Matsuo , and Kenji Kadomatsu ^*1

Departments of *Biochemistry and Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan

¹ To whom correspondence should be addressed. E-mail: kkadoma{at}med.nagoya-u.ac.jp.

	Abstract

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 N-linked 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 N-linked 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.