The E-selectin ligand basigin/CD147 is responsible for neutrophil recruitment in renal ischemia/reperfusion.
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.
Kato
Noritoshi
N
Department of Biochemistry, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
Yuzawa
Yukio
Y
Kosugi
Tomoki
T
Hobo
Akinori
A
Sato
Waichi
W
Miwa
Yuko
Y
Sakamoto
Kazuma
K
Matsuo
Seiichi
S
Kadomatsu
Kenji
K
D058186:Acute Kidney Injury / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology*; D014471:Umbilical Veins / Q000166:cytology
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D008024:Ligands; D051926:Basigin