Korean J Intern Med.  2017 Nov;32(6):1053-1061. 10.3904/kjim.2016.060.

Blocking junctional adhesion molecule C promotes the recovery of cisplatin-induced acute kidney injury

• Kim SC
• Ko YS
• Lee HY
• Kim MG
• Jo SK
• Cho WY

• KMID: 2396765
• DOI: http://doi.org/10.3904/kjim.2016.060

Abstract

BACKGROUND/AIMS
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.

Keyword

Junctional adhesion molecule C; Transendothelial and transepithelial migration; Cisplatin; Acute kidney injury

MeSH Terms

Acute Kidney Injury*
Animals
Antibodies
Cisplatin
Creatinine
Immunoglobulin G
Inflammation
Injections, Intraperitoneal
Junctional Adhesion Molecule C*
Junctional Adhesion Molecules*
Kidney
Mice
Neutrophil Infiltration
Neutrophils
Transendothelial and Transepithelial Migration
Antibodies
Cisplatin
Creatinine
Immunoglobulin G
Junctional Adhesion Molecule C
Junctional Adhesion Molecules