TY - JOUR
T1 - Elongated neutrophil-derived structures are blood-borne microparticles formed by rolling neutrophils during sepsis
AU - Marki, Alex
AU - Buscher, Konrad
AU - Lorenzini, Cristina
AU - Meyer, Matthew
AU - Saigusa, Ryosuke
AU - Fan, Zhichao
AU - Yeh, Yi Ting
AU - Hartmann, Nadine
AU - Dan, Jennifer M.
AU - Kiosses, William B.
AU - Golden, Gregory J.
AU - Ganesan, Rajee
AU - Winkels, Holger
AU - Orecchioni, Marco
AU - McArdle, Sara
AU - Mikulski, Zbigniew
AU - Altman, Yoav
AU - Bui, Jack
AU - Kronenberg, Mitchell
AU - Chien, Shu
AU - Esko, Jeffrey D.
AU - Nizet, Victor
AU - Smalley, David
AU - Roth, Johannes
AU - Ley, Klaus
N1 - Funding Information:
The Ley laboratory was supported by National Institutes of Health program project grants P01 HL078784 and P01 HL151433. A. Marki was supported by an American Heart Association postdoctoral fellowship (17POST33410940) and the Tullie and Rickey Families SPARK Award at La Jolla Institute for Immunology. H. Winkels was supported by Deutsche Forschungsgemeinschaft award GZ WI 4811/1-1. M. Orecchioni was supported by an American Heart Association postdoctoral fellowship 18POST34060251. Z. Fan was supported by National Institutes of Health grant R01HL145454 and American Heart Association postdoctoral fellowship and career development awards 16POST31160014 and 18CDA34110426. The purchase of the Zeiss LSM 880 microscope was made possible by National Institutes of Health grant S10OD021831 awarded to the Microscopy Core Facility at the La Jolla Institute.
Publisher Copyright:
© 2020 Marki et al.
PY - 2021/3/1
Y1 - 2021/3/1
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20200551
DO - 10.1084/jem.20200551
M3 - Article
C2 - 33275138
AN - SCOPUS:85097311131
SN - 0022-1007
VL - 218
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 3
M1 - e20200551
ER -