Ikegame, A. | Search bioRxiv

bioRxiv2025

Proteinase 3 is involved in presepsin production through neutrophil extracellular trap phagocytosis by macrophages

Presepsin (P-SEP), a soluble subtype of CD14, has been widely reported as a useful biomarker for sepsis in clinical studies. However, the cytological mechanism underlying its production remains poorly understood. Previous research has demonstrated that P-SEP is generated when M1 macrophages (M1 M{Phi}s) phagocytose neutrophil extracellular traps (NETs) and degrade internalized CD14. In this study, we demonstrated that M1 M{Phi}s phagocytose NETs and that proteinase 3 (PR3) within M1 M{Phi}s degrades NET-derived CD14, resulting in the production of P-SEP. Furthermore, we observed a strong correlation between the amount of NETs and P-SEP levels, indicating that NET phagocytosis is a key process in P-SEP generation. Our findings also suggest that PR3 released extracellularly along with NETs may degrade CD14 in plasma, contributing to elevated P-SEP levels. This mechanism may contribute to increased P-SEP concentrations observed in autoimmune diseases associated with NET accumulation, proposing P-SEP as a potential biomarker of disease activity beyond sepsis.

cell biology↗

bioRxiv2019

Clinical evaluation of presepsin considering renal function.

Presepsin, a glycoprotein produced during bacterial phagocytosis, has attracted attention as a sepsis marker for bacterial infections. However, since presepsin is affected by renal function, there is a need to separate the evaluation criteria for diagnosis of healthy subjects from that of patients with renal disorder. In this study, we analyzed the influence of kidney function on presepsin concentrations and recalculated the reference range based on the findings. For this purpose, EDTA-whole blood from 47 healthy subjects and 85 patients with chronic kidney disease was collected and used for presepsin measurement by PATHFAST. Presepsin was found to be significantly correlated with creatinine (r = 0.834), eGFRcreat (r = 0.837), cystatin-C (r = 0.845) and eGFRcys (r = 0.879).\n\nFurthermore, in patients with chronic kidney disease at different glomerular filtration rate stages, the presepsin levels showed a significant increasing trend with advancing glomerular filtration rate stage. The reference range, calculated by nonparametric method using a total of 67 cases of healthy volunteers and patients with chronic kidney disease G1, was found to be 59-153 pg/mL, which was notably lower than the standard reference range currently used. Presepsin concentrations were positively correlated with some biomarkers of renal function, indicating that it is necessary to consider the influence of renal function in patients with renal impairment. Further, the recalculated reference range might be more useful for diagnosis and treatment of sepsis than the standard reference currently in use, which likely includes false high values.

biochemistry↗