TY - JOUR
T1 - Interferon-α Inhibits NET Formation in Neutrophils Derived from Patients with Myeloproliferative Neoplasms in a Neutrophil Sub-Population-Specific Manner
AU - Partouche, Shirly
AU - Goldberg, Idan
AU - Halperin, Erez
AU - Atamna, Bahaa
AU - Shacham-Abulafia, Adi
AU - Shapira, Saar
AU - Samara, Aladin
AU - Gover-Proaktor, Ayala
AU - Leader, Avi
AU - Spectre, Galia
AU - Raanani, Pia
AU - Granot, Galit
AU - Wolach, Ofir
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/12
Y1 - 2024/12
N2 - Neutrophils and neutrophil extracellular traps (NETs) contribute to thrombosis and hyperinflammation in myeloproliferative neoplasms (MPN). High-density neutrophils (HDNs) and low-density neutrophils (LDNs) have recently been characterized as distinct neutrophil sub-populations with distinct morphological and functional properties. We aim to study the kinetics of NET formation and inhibition with interferon-α (IFNα) in neutrophils derived from patients with MPN as compared to matched healthy controls. Ex vivo NET formation was assessed by neutrophil-elastase activity, neutrophil-associated nucleosomes, myeloperoxidase (MPO), and citrullinated histone H3 content. IFNα significantly inhibited NET formation in neutrophils derived from MPN patients. Neutrophil sub-population analysis demonstrated that HDNs drive the increase in NET formation as compared to LDNs in patients and in healthy controls and are effectively inhibited by IFNα, an effect that is lost in LDNs. In conclusion, we demonstrate that in MPN, HDNs drive excess NET formation and are more sensitive to IFNα inhibition. These observations uncover unique neutrophil sub-population biology and dynamics in MPN.
AB - Neutrophils and neutrophil extracellular traps (NETs) contribute to thrombosis and hyperinflammation in myeloproliferative neoplasms (MPN). High-density neutrophils (HDNs) and low-density neutrophils (LDNs) have recently been characterized as distinct neutrophil sub-populations with distinct morphological and functional properties. We aim to study the kinetics of NET formation and inhibition with interferon-α (IFNα) in neutrophils derived from patients with MPN as compared to matched healthy controls. Ex vivo NET formation was assessed by neutrophil-elastase activity, neutrophil-associated nucleosomes, myeloperoxidase (MPO), and citrullinated histone H3 content. IFNα significantly inhibited NET formation in neutrophils derived from MPN patients. Neutrophil sub-population analysis demonstrated that HDNs drive the increase in NET formation as compared to LDNs in patients and in healthy controls and are effectively inhibited by IFNα, an effect that is lost in LDNs. In conclusion, we demonstrate that in MPN, HDNs drive excess NET formation and are more sensitive to IFNα inhibition. These observations uncover unique neutrophil sub-population biology and dynamics in MPN.
KW - high-density neutrophils
KW - interferon-α
KW - myeloproliferative neoplasia
KW - neutrophil extracellular traps
UR - http://www.scopus.com/inward/record.url?scp=85213228200&partnerID=8YFLogxK
U2 - 10.3390/ijms252413473
DO - 10.3390/ijms252413473
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AN - SCOPUS:85213228200
SN - 1661-6596
VL - 25
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 24
M1 - 13473
ER -