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bioRxiv · 10.1101/2025.05.02.651854

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

Ikegame, A.·Kondo, A.·Morinishi, T.·Yamaguchi, Y.·Okutani, Y.·Maegawa, C.·Tada, S.
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Abstract

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.

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Ikegame, A., Kondo, A., Morinishi, T., Yamaguchi, Y., Okutani, Y., Maegawa, C., Tada, S.. 2025-05-03. Proteinase 3 is involved in presepsin production through neutrophil extracellular trap phagocytosis by macrophages. https://doi.org/10.1101/2025.05.02.651854

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