Background Activated human eosinophils, as well as neutrophils, can release extracellular chromatin to form DNA traps through cytolytic extracellular trap cell death (ETosis). Although formations of neutrophil DNA traps are recognized in various inflammatory conditions, neither the presence of ETosis-derived eosinophil DNA traps in human allergic diseases nor the characteristics of these DNA traps have been studied. Objective We investigated the presence of ETosis-derived DNA traps in eosinophil-rich sinus and ear secretions and the functional attributes of ETosis DNA traps. Methods Eosinophil-rich secretions obtained from patients with eosinophilic chronic rhinosinusitis (ECRS) and eosinophilic otitis media (EOM) were studied microscopically. In vitro studies of ETosis and DNA trap formation used blood-derived eosinophils and neutrophils, and binding capacities of DNA traps used labeled bacteria and fluorescent microbeads. Stabilities of DNA traps were evaluated by fluorescence microscopy. Results Abundant nuclear histone H1-bearing DNA traps had formed in vivo in the eosinophilic secretions and contributed to their increased viscosity. In vitro, following brief shear flow, eosinophil ETosis-elicited DNA traps assembled to form stable aggregates. Eosinophil DNA traps entrapped bacteria and fungi and by hydrophobic interactions microbeads. In comparison with neutrophil-derived DNA traps, eosinophil DNA traps ultrastructurally exhibited thicker fibers with globular structures and were less susceptible to leukocyte-derived proteolytic degradation, likely due to the lesser protease activities of eosinophils. Conclusions In human allergic diseases, the local cytolysis of eosinophils not only releases free eosinophil granules but also generates nuclear-derived DNA traps that are major extracellular structural components within eosinophil-rich secretions.

Pure red cell aplasia (PRCA) is a syndrome characterized by a severe normocytic anaemia, reticulocytopenia, and absence of erythroblasts from an otherwise normal bone marrow. Primary PRCA, or secondary PRCA which has not responded to treatment of the underlying disease, is treated as an immunologically-mediated disease. Although vigorous immunosuppressive treatments induce and maintain remissions in a majority of patients, they carry an increased risk of serious complications. Corticosteroids were used in the treatment of PRCA and this has been considered the treatment of first choice although relapse is not uncommon. Cyclosporine A (CsA) has become established as one of the leading drugs for treatment of PRCA. However, common concerns have been the number of patients treated with CsA who achieve sustained remissions and the number that relapse. This article reviews the current status of CsA therapy and compares it to other treatments for diverse PRCAs.

Abstract Protein crystallization in human tissue rarely occurs. Charcot-Leyden crystals (CLCs) were described in various eosinophilic diseases >150 years ago, but our understanding of CLC formation still remains limited. In this study, we demonstrate that CLCs observed in varied inflamed human tissues are closely associated with eosinophil cell-free granules and nuclear envelope/plasma membrane disintegration with release of filamentous chromatin (extracellular traps), typical morphologies of a regulated pathway of extracellular trap cell death (ETosis). During the process of eosinophil ETosis, eccentrically localized cytoplasmic and perinuclear CLC protein (galectin-10) is homogeneously redistributed in the cytoplasm. Rapid (1-2 minutes) formation of intracytoplasmic CLCs was observed using time-lapse imaging. Plasma membrane rupture enabled the release of both intracellularly formed CLCs and soluble galectin-10 that further contributed to formation of CLCs extracellularly, in parallel with the expulsion of free intact granules and extracellular traps. CLC formation and galectin-10 release were dependent on nicotinamide adenine dinucleotide phosphate oxidase activation. To our knowledge, this is the first demonstration of natural formation of CLCs in association with an active physiological process (ie, ETosis). These results indicate that dynamic changes in intracellular localization and release of galectin-10 contribute to CLC formation in vivo and suggest that CLC/galectin-10 might serve as an indicator of ETosis.

BackgroundAlthough the AB0 blood group is one of two major antigen systems of relevance for transplantation in humans, there are still conflicting data concerning the influence of AB0 incompatibility on transplant outcome. This study investigated the effect of AB0 incompatibility in recipients of bone marrow transplants from unrelated donors.