Study in the role of extracellular histones in the pathogenesis of acute lung injury caused by acid aspiration

Abstract

Objective To investigate the effects of extracellular histones as a major mediator and the target for intervention in the pathogenesis of ALI in the wake of acid aspiration. Methods The correlation of circulating histones and aspiratory acid was determined with normal saline and 4 different concentrations of acid (0.01 mol/L, 0.1 mol/L, 0.3 mol/L and 0.5 mol/L) . The dynamic change of circulating histones was observed at 6 intervals of 1, 3, 6, 12, 24 and 72 h after injury. The protection of anti-histone-4 antibody was assessed by survival rates, blood gas, lung edema, MPO activity and lung pathological change. Results After acid aspiration, extracellular histone H4 increased significantly. The circulating histone levels were closely correlative with the concentrations of aspiratory acid (r =0.874 6, P =0.031 7) . The anti-histone-4 antibody could decrease mortality (P =0.034 5) and improve blood gas, lung edema, MPO activity and lung pathological change. Conclusions The results showed that extracellular histones were not only the key mediators in the pathogenesis of ALI but also the target for intervention. Key words: Extracellular histones; Acute lung injury; Acid aspiration; Inflammation; Neutralizing antibody