Dynamic neutrophil lipidome remodeling during induction of NETosis.

Authors

Patrick Münzer, Cristina Coman, Gundula D Lingens, Nina N Troppmair, Jesse A Michael, Reuben S E Young, Stefanie Rubenzucker, Jens Martin, Jann Arden, Melina Fischer, Nils Sülzle, Ferdinand Kollotzek, Monika Zdanyte, Claudia Hornef, Shane R Ellis, Oliver Borst, Robert Ahrends

Published in

Science advances. Volume 12. Issue 26. Pages eaec9891. Jun 26, 2026. Epub Jun 24, 2026.

Abstract

Neutrophil extracellular trap formation (NETosis) affects a wide variety of clinically relevant human diseases. Although lipid remodeling is essential for neutrophil function and membrane rupture during NETosis, the neutrophil lipidome and its dynamics have not been characterized. Thus, we establish a quantitative lipidome of human neutrophils comprising 1048 species across nine orders of magnitude and map its remodeling during NETosis. NET formation caused profound alterations in the phosphatidylinositol, phosphatidic acid, diacylglycerol (DG), and lyso-glycerophospholipid levels. Calcium- and reactive oxygen species-dependent NETosis pathways displayed distinct lipidomic trajectories yet converged on the significance of phospholipid lipase networks. Pharmacological inhibition of this networks altered lipid composition and markedly impaired NETosis, while DG treatment revoked the effect. Together, our findings reveal lipid remodeling as a fundamental determinant of NETosis and identify interconnected and dependent phospholipid lipase networks with downstream DG-dependent signaling as a potential therapeutic target in NET-associated diseases.

PMID:
42341139
Bibliographic data and abstract were imported from PubMed on 25 Jun 2026.

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