Elucidation of a Novel Mechanism of Presepsin Production by Monocyte/macrophage Phagocytosis of Neutrophil Extracellular Traps

Abstract Presepsin, a biomarker discovered in Japan, has been clinically applied as a diagnostic aid for sepsis. Recently, however, it has been reported that presepsin levels are elevated in patients with severe systemic lupus erythematosus without infection, suggesting the existence of a production mechanism that does not involve bacterial phagocytosis. In this study, we aimed to elucidate the mechanism of presepsin production without bacterial phagocytosis and explore the clinical significance of presepsin. Neutrophil extracellular traps (NETs) were induced by Escherichia coli and phorbol myristate acetate (PMA) in neutrophils isolated from the peripheral blood of healthy subjects. NET induction alone did not increase presepsin levels, but co-culturing with monocytes significantly increased them. The addition of a NET formation inhibitor also suppressed presepsin levels, suggesting that presepsin production is greatly influenced by monocyte phagocytosis of NETs. Phagocytosis of NETs by THP-1 and U937 cells, which was induced by CD14 expression, also increased presepsin levels. This study suggests that presepsin can be used to assess the severity of inflammatory diseases, such as autoimmune diseases, and monitor treatment effects.