IntroductionSurfactant protein D (SP-D) is expressed in the lung and plays important roles in innate immunity including defense against inhaled pathogens. While the levels of SP-D have been shown to decrease in acutely injured lung, little is known about the mechanism(s) of its inactivation and clearance. A hall-mark of acute inflammation is the recruitment and activation of polymorphonuclear neutrophils (PMNs). Activated PMNs employ different pathways to generate toxic oxidants with deleterious effect on host tissues. In the myeloperoxidase (MPO) pathway, MPO employs hydrogen peroxide (H2O2) and chloride to generate HOC1, a highly reactive and toxic oxidant. These observations prompted us to hypothesize that MPO-derived oxidants can alter the structure and function of SP-D.Experimental design and resultsTo test our hypothesis, we exposed purified human or rat SP-D to HOC1 or MPO System (MPO+H2O2+Chloride ions). Next, the activity of treated SP-D was examined using two well-characterizedin vitroassays: bacterial agglutination and binding to solid phase yeast mannan Both HOC1 and MPO System abrogated SP-D's ability to aggregate bacteria and decreased its ability to bind to mannan. Additional studies using mutant SP-D suggest oxidative inactivation of SP-D C-type lectin region, the carbohydrate recognition domain (CRD). In contrast to HOC1, H2O2had no effect on SP-D function at ail concentrations examined. Moreover, electrophoretic analysis of HOCl-treated SP-D demonstrated high molecular weight complexes by comparison to control SP-D.ConclusionOur data suggest that MPO-derived oxidants such as HOC1 target SP-D within its CRD region and broadly interferes with its function(s). Studies are underway to investigate the mechanism(s) of oxidative inactivation of SP-D.