Eosinophil extracellular trap cell death–derived DNA traps: Their presence in secretions and functional attributes

Background Activated human eosinophils, as well as neutrophils, can release extracellular chromatin to form DNA trapsthrough cytolytic extracellular trapcell death (ETosis). Although formations of neutrophil DNA trapsare recognized in patients with various inflammatory conditions, neither the presence of ETosis-derived eosinophil DNA trapsin human allergic diseases nor the characteristics of these DNA trapshave been studied. Objective We investigated the presence of ETosis-derived DNA trapsin eosinophil-rich sinus and ear secretions and the functional attributes of ETosis DNA traps. Methods Eosinophil-rich secretions obtained from patients with eosinophilicchronic rhinosinusitis and eosinophilicotitis media were studied microscopically. In vitro studies of ETosis and DNA trapformation used blood-derived eosinophilsand neutrophils, and studies of the binding capacities of DNA trapsused labeled bacteria and fluorescent microbeads. Stabilities of DNA trapswere evaluated by using fluorescence microscopy. Results Abundant nuclear histone H1–bearing DNA trapsformed in vivo in the eosinophilicsecretions and contributed to their increased viscosity. In vitro , after brief shear flow, eosinophilETosis-elicited DNA trapsassembled to form stable aggregates. Eosinophil DNA trapsentrapped bacteria and fungi and, through hydrophobic interactions, microbeads. In comparison with neutrophil-derived DNA traps, eosinophil DNA trapsultrastructurally exhibited thicker fibers with globular structures and were less susceptible to leukocyte-derived proteolytic degradation, likely because of the lesser protease activities of eosinophils. Conclusions In human allergic diseases local cytolysisof eosinophilsnot only releases free eosinophilgranules but also generates nuclear-derived DNA trapsthat are major extracellular structural components within eosinophil-rich secretions.