Elongated neutrophil-derived structures are blood-borne microparticles formed by rolling neutrophils during sepsis

Alex Marki, Konrad Buscher, Cristina Lorenzini, Matthew Meyer, Ryosuke Saigusa, Zhichao Fan, Yi Ting Yeh, Nadine Hartmann, Jennifer M. Dan, William B. Kiosses, Gregory J. Golden, Rajee Ganesan, Holger Winkels, Marco Orecchioni, Sara McArdle, Zbigniew Mikulski, Yoav Altman, Jack Bui, Mitchell Kronenberg, Shu ChienJeffrey D. Esko, Victor Nizet, David Smalley, Johannes Roth, Klaus Ley

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Rolling neutrophils form tethers with submicron diameters. Here, we report that these tethers detach, forming elongated neutrophil-derived structures (ENDS) in the vessel lumen. We studied ENDS formation in mice and humans in vitro and in vivo. ENDS do not contain mitochondria, endoplasmic reticulum, or DNA, but are enriched for S100A8, S100A9, and 57 other proteins. Within hours of formation, ENDS round up, and some of them begin to present phosphatidylserine on their surface (detected by annexin-5 binding) and release S100A8–S100A9 complex, a damage-associated molecular pattern protein that is a known biomarker of neutrophilic inflammation. ENDS appear in blood plasma of mice upon induction of septic shock. Compared with healthy donors, ENDS are 10–100-fold elevated in blood plasma of septic patients. Unlike neutrophil-derived extracellular vesicles, most ENDS are negative for the tetraspanins CD9, CD63, and CD81. We conclude that ENDS are a new class of bloodborne submicron particles with a formation mechanism linked to neutrophil rolling on the vessel wall.

Original languageEnglish (US)
Article numbere20200551
JournalJournal of Experimental Medicine
Issue number3
StatePublished - Mar 1 2021
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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