title: Phagocytosis by human monocytes is required for the secretion of presepsin.
abstract: 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.
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Mizugishi
authors.affiliation: Discovery Research, Mochida Pharmaceuticals Co., Ltd, Gotemba, Shizuoka 412-8524, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nonomura
authors.affiliation: Discovery Research, Mochida Pharmaceuticals Co., Ltd, Gotemba, Shizuoka 412-8524, Japan.
authors.forename: Katsuki
authors.initials: K
authors.lastname: Naitoh
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Takaori-Kondo
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. Electronic address: kouhei@kuhp.kyoto-u.ac.jp.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Yamashita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016470:Bacteremia / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D004926:Escherichia coli; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D018950:Lipopolysaccharide Receptors; D051359:Lymphohistiocytosis, Hemophagocytic / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology; D010196:Pancreatic Elastase / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D010587:Phagocytosis; D013212:Staphylococcus epidermidis; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018950:Lipopolysaccharide Receptors; D010446:Peptide Fragments; C000594167:presepsin protein, human; D010196:Pancreatic Elastase
keywords: Hematopoietic cell transplantation; Hemophagocytic syndrome; Monocyte; Phagocytosis; Presepsin; Sepsis