TY - JOUR
T1 - Lack of eosinophil extracellular trap formation due to failure of plasma membrane breakdown in the absence of elastase
AU - Sprenkeler, Evelien G. G.
AU - Goetschalckx, Ines
AU - Fernández Hermira, Sara
AU - Tool, Anton T. J.
AU - Hoogenboezem, Mark
AU - van Bruggen, Robin
AU - Kuijpers, Taco W.
N1 - Funding Information: E.G.G.S. and T.W.K. were partially supported by funds from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement number 668303 and T.W.K. was partially funded by the E-Rare ZonMW grant #90030376506. Publisher Copyright: © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
PY - 2023/10/10
Y1 - 2023/10/10
N2 - Activated eosinophils are described to release eosinophil extracellular traps (EETs), which consist of the cell’s DNA covered with granule-derived antimicrobial peptides. Upon stimulation of eosinophils with the known EET-inducers phorbol 12-myristate 13-acetate, monosodium urate crystals, or Candida albicans, we observed that their plasma membrane became compromised, resulting in accessibility of the nuclear DNA for staining with the impermeable DNA dye Sytox Green. However, we did not observe any DNA decondensation or plasma membrane rupture by eosinophils, which sharply contrasts with neutrophil extracellular trap (NET) formation and the subsequent cell death known as NETosis. Neutrophil elastase (NE) activity is thought to be essential for the cleavage of histones and chromatin decondensation during NETosis. We observed that the neutrophils of a patient with a mutation in ELANE, leading to congenital neutropenia and NE deficiency, were unable to undergo NETosis. Taken together, we may suggest that the natural absence of any NE-like proteolytic activity in human eosinophils explains why EET formation is not observed, even when eosinophils become positive for an impermeable DNA dye in response to stimuli that induce NETosis in neutrophils.
AB - Activated eosinophils are described to release eosinophil extracellular traps (EETs), which consist of the cell’s DNA covered with granule-derived antimicrobial peptides. Upon stimulation of eosinophils with the known EET-inducers phorbol 12-myristate 13-acetate, monosodium urate crystals, or Candida albicans, we observed that their plasma membrane became compromised, resulting in accessibility of the nuclear DNA for staining with the impermeable DNA dye Sytox Green. However, we did not observe any DNA decondensation or plasma membrane rupture by eosinophils, which sharply contrasts with neutrophil extracellular trap (NET) formation and the subsequent cell death known as NETosis. Neutrophil elastase (NE) activity is thought to be essential for the cleavage of histones and chromatin decondensation during NETosis. We observed that the neutrophils of a patient with a mutation in ELANE, leading to congenital neutropenia and NE deficiency, were unable to undergo NETosis. Taken together, we may suggest that the natural absence of any NE-like proteolytic activity in human eosinophils explains why EET formation is not observed, even when eosinophils become positive for an impermeable DNA dye in response to stimuli that induce NETosis in neutrophils.
UR - http://www.scopus.com/inward/record.url?scp=85173822908&partnerID=8YFLogxK
U2 - https://doi.org/10.1182/bloodadvances.2022009432
DO - https://doi.org/10.1182/bloodadvances.2022009432
M3 - Article
C2 - 37428870
SN - 2473-9529
VL - 7
SP - 5868
EP - 5876
JO - Blood advances
JF - Blood advances
IS - 19
ER -