Anti-S100A8/A9 Neutralizing Monoclonal Antibody Ameliorates Lung Injury Induced by Lung Ischemia Reperfusion Injury

Abstract

<h3>Purpose</h3> Lung ischemia reperfusion (IR) injury is inevitable in the lung transplant and increases the mortality and morbidity in patients undergoing lung transplantation. S100A8/A9 is one of the damage-associated molecular patterns which is known as an early inflammatory mediator in IR injury. The aim of this study was to assess the therapeutic effect of neutralizing monoclonal antibody (mAb) against S100A8/A9. <h3>Methods</h3> A mice hilar clamp model of IR was used. Animals were divided into sham groups and IR groups with or without administration of anti-S100A8/A9 mAb. We assessed lung oxygenation, tissue injury, neutrophil infiltrations, expression of proinflammatory molecules and apoptosis. <h3>Results</h3> Plasma S100A8/A9 level was significantly reduced by anti-S100A8/A9 mAb treatment. The severity of IR injury represented by oxygenation capacity was significantly improved by the antibody treatment (Figure 1). Anti-S100A8/A9 mAb treatment reduced the S100A8/A9 positive cells in lung tissue detected by anti-S100A9 antibody (Figure 2) and neutrophil infiltrations. The neutralizing antibody significantly suppressed IR gene expression levels of IR injury-induced proinflammatory factors including IL-1β, IL-6, TNF-α, CXCL-1 and CXCL-2. Further investigations unveiled that the abrogation of S100A8/A9 function decreased TUNEL-positive cells indicating apoptotic cells. <h3>Conclusion</h3> The anti-S100A8/A9 mAb obviously ameliorated lung IR injury by reduction of neutrophil infiltrations, inflammatory molecules and apoptosis, indicating that S100A8/A9 is a novel therapeutic target for lung IR injury.