title: Blocking junctional adhesion molecule C promotes the recovery of cisplatin-induced acute kidney injury.
abstract: OBJECTIVE
  Recent findings have demonstrated the occurrence of neutrophil transendothelial migration in the reverse direction (reverse TEM) and that endothelial junctional adhesion molecule C (JAM-C) is a negative regulator of reverse TEM. In this study, we tested the effects of a JAM-C blocking antibody on the resolution of kidney injuries and inflammation in a mouse model of cisplatin-induced acute kidney injury (AKI).
  
  
  METHODS
  Cisplatin was administered via intraperitoneal injection. A JAM-C blocking antibody or a control immunoglobulin G was administered intraperitoneal at 1.5 mg/kg, with the injection being delayed until day 4 following cisplatin administration to restrict the effect of antibodies on recovery.
  
  
  RESULTS
  After cisplatin injection, serum creatinine and histologic injuries peaked on day 4. Treatment with a JAM-C blocking antibody on days 4 and 5 promoted the functional and histologic recovery of cisplatin-induced AKI on days 5 and 6. Facilitating recovery with a JAM-C blocking antibody correlated with significantly increased circulating intercellular adhesion molecule 1+ Tamm-Horsfall protein+ neutrophils and significantly decreased renal neutrophil infiltration, indicating that facilitating reverse the TEM of neutrophils from the kidney to the peripheral circulation partially mediated the resolution of inflammation and recovery.
  
  
  CONCLUSIONS
  These results demonstrated that reverse TEM is involved in the resolution of neutrophilic inflammation in cisplatin-induced AKI and that JAM-C is an important regulator of this process.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea.
authors.forename: Sun Chul
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea.
authors.forename: Yoon Sook
authors.initials: YS
authors.lastname: Ko
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea.
authors.forename: Myung-Gyu
authors.initials: MG
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea.
authors.forename: Sang-Kyung
authors.initials: SK
authors.lastname: Jo
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea.
authors.forename: Won-Yong
authors.initials: WY
authors.lastname: Cho
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000276:immunology*; D000818:Animals; D002945:Cisplatin; D062786:Junctional Adhesion Molecule C / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology*
chemical_list: D062786:Junctional Adhesion Molecule C; D002945:Cisplatin
keywords: Acute kidney injury; Cisplatin; Junctional adhesion molecule C; Transendothelial and transepithelial migration