@article{APS6914,
author = {Xiao-mei Zhu and Yong-ming Yao and Li-tian Zhang and Ning Dong and Yan Yu and Zhi-yong Sheng},
title = {Anti-RAGE antibody ameliorates severe thermal injury in rats through regulating cellular immune function},
journal = {Acta Pharmacologica Sinica},
volume = {35},
number = {9},
year = {2016},
keywords = {},
abstract = {Xiao-mei ZHU, Yong-ming YAO*, Li-tian ZHANG, Ning DONG, Yan YU, Zhi-yong SHENG
Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China
Aim: The receptor of advanced glycation end products (RAGE) participates in a variety of pathophysiological processes and inflammatory responses. The aim of this study was to investigate the therapeutic potential of an anti-RAGE neutralizing antibody for severe thermal injury in rats, and to determine whether the treatment worked via modulating cellular immune function.
Methods: Full-thickness scald injury was induced in Wistar rats, which were treated with the anti-RAGE antibody (1 mg/kg, iv) at 6 h and 24 h after the injury. The rats were sacrificed on d 1, 3, 5, and 7. Blood and spleen samples were harvested to monitor organ function and to analyze dendritic cell (DC) and T cell cytokine profiles. The survival rate was analyzed up to d 7 after the injury.
Results: Administration of the antibody significantly increased the 7 d survival rate in thermally injured rats (6.67% in the model group; 33.33% in anti-RAGE group). Treatment with the antibody also attenuated the multiple organ dysfunction syndrome (MODS) following the thermal injury, as shown by significant decreases in the organ dysfunction markers, including serum ALT, AST, blood urea nitrogen, creatinine and CK-MB. Moreover, treatment with the antibody significantly promoted DC maturation and T cell activation in the spleens of thermally injured rats.
Conclusion: Blockade of the RAGE axis by the antibody effectively ameliorated MODS and improved the survival rate in thermally injured rats, which may be due to modulation of cellular immune function.
Keywords: RAGE; anti-RAGE antibody; burns; thermal injury; multiple organ dysfunction syndrome; cytokine; inflammation; immune response; dendritic cell; T cell
This study was supported by grants from the National Natural Science Foundation of China (No 81130035, 81272090, and 81372054), the National Basic Research Program of China (No 2012CB518102), the Beijing Nova Program (Z121107002512123), and the State Key Laboratory of Trauma, Burns, and Combined Injury, China (No SKLKF201103).
* To whom correspondence should be addressed.
E-mail c_ff@sina.com
Received 2014-01-25 Accepted 2014-05-12},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/6914}
}