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Therapeutic Effectiveness of Anti-RAGE Antibody Administration in a Rat Model of Crush Injury.

ABSTRACT: Crush injury patients often have systemic inflammatory response syndrome that leads to multiple organ failure. Receptor for advanced glycation endproducts (RAGE) functions as a pattern recognition receptor that regulates inflammation. We evaluated the effects of anti-RAGE antibody in a crush injury model. Pressure was applied to both hindlimbs of rats for 6?h by 3.0-kg blocks and then released. Animals were randomly divided into the sham (RAGE-Sh) group, crush (RAGE-Ctrl) group or anti-RAGE antibody-treated crush (RAGE-Tx) group. Samples were collected at 3, 6 and 24?h after releasing pressure. In the RAGE-Ctrl group, fluorescent immunostaining in the lung showed upregulated RAGE expression at 3?h. The serum soluble RAGE (sRAGE) level, which reflects the amount of RAGE expression in systemic tissue, increased at 6?h. Serum interleukin 6 (IL-6; systemic inflammation marker) increased immediately at 3?h. Histological analysis revealed lung injury at 6 and 24?h. Administration of anti-RAGE antibody before releasing compression inhibited upregulated RAGE expression in the lung alveoli, suppressed RAGE-associated mediators sRAGE and IL6, attenuated the lung damage and improved the 7-day survival rate. Collectively, our results indicated that the use of anti-RAGE antibody before releasing compression is associated with a favourable prognosis following crush injury.

SUBMITTER: Matsumoto H

PROVIDER: S-EPMC5613014 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Therapeutic Effectiveness of Anti-RAGE Antibody Administration in a Rat Model of Crush Injury.

Matsumoto Hisatake H Matsumoto Naoya N Shimazaki Junya J Nakagawa Junichiro J Imamura Yukio Y Yamakawa Kazuma K Yamada Tomoki T Ikeda Mitsunori M Hiraike Hiroko H Ogura Hiroshi H Shimazu Takeshi T

Scientific reports 20170925 1

Crush injury patients often have systemic inflammatory response syndrome that leads to multiple organ failure. Receptor for advanced glycation endproducts (RAGE) functions as a pattern recognition receptor that regulates inflammation. We evaluated the effects of anti-RAGE antibody in a crush injury model. Pressure was applied to both hindlimbs of rats for 6 h by 3.0-kg blocks and then released. Animals were randomly divided into the sham (RAGE-Sh) group, crush (RAGE-Ctrl) group or anti-RAGE anti ...[more]

PMID: 28947744

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Dataset Information

Therapeutic Effectiveness of Anti-RAGE Antibody Administration in a Rat Model of Crush Injury.

Publications

Therapeutic Effectiveness of Anti-RAGE Antibody Administration in a Rat Model of Crush Injury.

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