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Anti-RAGE antibody ameliorates severe thermal injury in rats through regulating cellular immune function.

Zhu XM, Yao YM, Zhang LT, Dong N, Yu Y, Sheng ZY - Acta Pharmacol. Sin. (2014)

Bottom Line: Blood and spleen samples were harvested to monitor organ function and to analyze dendritic cell (DC) and T cell cytokine profiles.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China.

ABSTRACT

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.

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Related in: MedlinePlus

Effect of anti-RAGE treatment on T cell activation after thermal injury. T cells isolated from rat spleens on PBD 1, 3, 5, and 7 were cultured with Con A for 18 h at 37 °C. The level of IL-2 in the cell culture supernatants was measured by ELISA. IL-2 and IL-2Rα mRNA levels were measured by real-time PCR. IL-2Rα expression on surface of T was also measured by flow cytometry after incubation with PE anti-rat CD25 and FITC anti-rat CD3. The results are shown as the mean±SD (n=6). bP<0.05 vs the sham control group. eP<0.05 vs the thermal injury group.
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fig9: Effect of anti-RAGE treatment on T cell activation after thermal injury. T cells isolated from rat spleens on PBD 1, 3, 5, and 7 were cultured with Con A for 18 h at 37 °C. The level of IL-2 in the cell culture supernatants was measured by ELISA. IL-2 and IL-2Rα mRNA levels were measured by real-time PCR. IL-2Rα expression on surface of T was also measured by flow cytometry after incubation with PE anti-rat CD25 and FITC anti-rat CD3. The results are shown as the mean±SD (n=6). bP<0.05 vs the sham control group. eP<0.05 vs the thermal injury group.

Mentions: To understand the potential effect of anti-RAGE antibody treatment on T cell-mediated immunity, we analyzed T cell proliferation and cytokine production. Proliferation in response to Con A was significantly decreased in T cells isolated from thermally injured rats over PBD 1–7 compared to T cells isolated from the sham operation group (Figure 8). And as shown in Figure 9, IL-2 mRNA and protein expression, IL-2Rα mRNA expression by T cells, and IL-2Rα expression on the surface of T cells were somewhat suppressed following thermal injury, and treatment with the anti-RAGE antibody restored normal expression levels (all P<0.05). Conversely, the level of serum sIL-2R expression decreased initially on PBD 1 and then rapidly increased over PBD 3–7, peaking on PBD 3. Treatment with the anti-RAGE antibody markedly decreased the level of serum sIL-2R levels induced by thermal injury (all P<0.05). These data suggest that blocking RAGE could restore T cell activation secondary to acute insults.


Anti-RAGE antibody ameliorates severe thermal injury in rats through regulating cellular immune function.

Zhu XM, Yao YM, Zhang LT, Dong N, Yu Y, Sheng ZY - Acta Pharmacol. Sin. (2014)

Effect of anti-RAGE treatment on T cell activation after thermal injury. T cells isolated from rat spleens on PBD 1, 3, 5, and 7 were cultured with Con A for 18 h at 37 °C. The level of IL-2 in the cell culture supernatants was measured by ELISA. IL-2 and IL-2Rα mRNA levels were measured by real-time PCR. IL-2Rα expression on surface of T was also measured by flow cytometry after incubation with PE anti-rat CD25 and FITC anti-rat CD3. The results are shown as the mean±SD (n=6). bP<0.05 vs the sham control group. eP<0.05 vs the thermal injury group.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4155528&req=5

fig9: Effect of anti-RAGE treatment on T cell activation after thermal injury. T cells isolated from rat spleens on PBD 1, 3, 5, and 7 were cultured with Con A for 18 h at 37 °C. The level of IL-2 in the cell culture supernatants was measured by ELISA. IL-2 and IL-2Rα mRNA levels were measured by real-time PCR. IL-2Rα expression on surface of T was also measured by flow cytometry after incubation with PE anti-rat CD25 and FITC anti-rat CD3. The results are shown as the mean±SD (n=6). bP<0.05 vs the sham control group. eP<0.05 vs the thermal injury group.
Mentions: To understand the potential effect of anti-RAGE antibody treatment on T cell-mediated immunity, we analyzed T cell proliferation and cytokine production. Proliferation in response to Con A was significantly decreased in T cells isolated from thermally injured rats over PBD 1–7 compared to T cells isolated from the sham operation group (Figure 8). And as shown in Figure 9, IL-2 mRNA and protein expression, IL-2Rα mRNA expression by T cells, and IL-2Rα expression on the surface of T cells were somewhat suppressed following thermal injury, and treatment with the anti-RAGE antibody restored normal expression levels (all P<0.05). Conversely, the level of serum sIL-2R expression decreased initially on PBD 1 and then rapidly increased over PBD 3–7, peaking on PBD 3. Treatment with the anti-RAGE antibody markedly decreased the level of serum sIL-2R levels induced by thermal injury (all P<0.05). These data suggest that blocking RAGE could restore T cell activation secondary to acute insults.

Bottom Line: Blood and spleen samples were harvested to monitor organ function and to analyze dendritic cell (DC) and T cell cytokine profiles.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus