Phagocytosis by human monocytes is required for the secretion of presepsin

Background: Presepsin, a soluble CD14 subtype, is increasingly recognized as a useful biomarker for sepsis. However, little is known about the biological characteristics of presepsin in humans. Furthermore, there are no studies evaluating clinical validity of measuring the presepsin levels in patients after allogeneic hematopoietic cell transplantation, irrespective of the high frequency of sepsis. Methods: For in vitro assays, neutrophils and monocytes were isolated from the peripheral blood of healthy controls and treated with bacteria or inflammatory stimuli. Presepsin levels in the culture supernatants were measured by enzyme linked immunosorbent assay (ELISA). For a cohort study of patients undergoing allogeneic hematopoietic cell transplantation, serum samples were subjected to ELISA for presepsin, and the relationship of presepsin levels with the incidence of transplantation-related complications was statistically analyzed. Results: We found that monocytes were the main source of presepsin in humans. Presepsin secretion by human monocytes was triggered by bacterial phagocytosis or sterile phagocytic stimulus, such as monosodium urate crystals, rather than soluble inflammatory stimuli. Elastase, a serine protease in human monocytes, mediated CD14 cleavage to produce presepsin. The cohort study demonstrated that high presepsin values were significantly associated with an increased incidence of hemophagocytic syndrome, as well as bacteremia. Moreover, patients with higher presepsin values revealed inferior overall survival, suggesting that presepsin can also be a prognostic marker for transplantation. Conclusions: In this study, we clarified the biological features of presepsin in humans. Our study may be useful for increasing the clinical application of presepsin as a biomarker. (C) 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.