Experimental murine acid aspiration injury is mediated by neutrophils and the alternative complement pathway

Weiser, Martin R., Taine T. V. Pechet, Julian P. Williams,Minghe Ma, Paul S. Frenette, Francis D. Moore, Lester Kobzik, RichardO. Hines, Denisa D. Wagner, Michael C. Carroll, and Herbert B. Hechtman. Experimental murine acid aspiration injury is mediatedby neutrophils and the alternative complement pathway. J. Appl. Physiol. 83(4):1090-1095, 1997.Acid aspiration may result in the development ofthe acute respiratory distress syndrome, an event associated withsignificant morbidity and mortality. Although once attributed to directdistal airway injury, the pulmonary failure after acid aspiration ismore complex and involves an inflammatory injury mediated by complement(C) and polymorphonuclear leukocytes. This study examines the injuriousinflammatory cascades that are activated after acid aspiration. Therole of neutrophils was defined by immunodepletion before aspiration,which reduced injury by 59%. The injury was not modified in either P-or E-selectin-knockout mice, indicating that these adhesion moleculeswere not operative. C activation after aspiration was documented withimmunochemistry by C3 deposition on injured alveolar pneumocytes.Animals in which C activation was inhibited with soluble C receptortype 1 (sCR1) had a 54% reduction in injury, similar to the level ofprotection seen in C3-knockout mice (58%). However C4-knockout micewere not protected from injury, indicating that C activation ismediated by the alternative pathway. Finally, an additive effect ofneutrophils and C was demonstrated whereby neutropenic animals thatwere treated with sCR1 showed an 85% reduction in injury. Thus acidaspiration injury is mediated by neutrophils and the alternative Cpathway.