Anti-HMGB1 Monoclonal Antibody Ameliorates Lung Ischemia Reperfusion Injury in Mice

Abstract

Purpose Lung ischemia reperfusion (IR) injury increases the mortality and morbidity in patients undergoing lung transplantation. Inflammatory mediators called Damage Associated Molecular Patterns (DAMPs) concern with inflammatory response to develop the organ damages during IR injury and High Mobility Group Box 1 (HMGB1) is one of the most important DAMPs. We had previously developed anti-HMGB1 monoclonal antibody (mAb) and assessed the therapeutic effect of the antibody in lung IR injury. Methods A mice hilar clamp model of IR was used, and animals were divided into sham groups and IR groups with or without administration of anti-HMGB 1 mAb. We analyzed the effect of anti-HMGB 1 mAb against IR injury by assessing lung oxygenation, injury, neutrophil infiltrations, expression of proinflammatory cytokines and chemokines, MAPK signaling and apoptosis. Results The severity of IR injury represented by oxygenation capacity, lung injury score and neutrophil infiltrations was significantly improved by anti-HMGB1 mAb treatment. The expressions of proinflammatory factors including IL-1b, IL-6, IL-12, TNFα, CXCL1 and CXCL2 and phosphorylation of p38 MAPK were significantly reduced by the anti-HMGB1 mAb treatment. Furthermore, the antibody decreased TUNEL positive cells to detect apoptosis. Conclusion Anti-HMGB1 mAb obviously ameliorated lung IR injury by reduction of inflammatory responses and apoptosis. Our findings indicate that anti-HMGB1 mAb have a potential as therapeutic drug to improve IR injury in lung transplantation.