Interferon-α inhibits NET formation in neutrophils derived from patients with myeloproliferative neoplasms in a neutrophil sub-population-specific manner Journal Article
| Authors: | Partouche, S.; Goldberg, I.; Halperin, E.; Atamna, B.; Shacham-Abulafia, A.; Shapira, S.; Samara, A.; Gover-Proaktor, A.; Leader, A.; Spectre, G.; Raanani, P.; Granot, G.; Wolach, O. |
| Article Title: | Interferon-α inhibits NET formation in neutrophils derived from patients with myeloproliferative neoplasms in a neutrophil sub-population-specific manner |
| Abstract: | 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. © 2024 by the authors. |
| Keywords: | adult; clinical article; controlled study; aged; middle aged; myeloproliferative disorders; human cell; myeloproliferative disorder; alpha interferon; peroxidase; metabolism; myeloperoxidase; practice guideline; drug effect; pathology; neutrophil; histone; histone h3; neutrophils; ex vivo study; population dynamics; histones; myeloproliferative neoplasm; thrombocytosis; polycythemia vera; interferon-alpha; phorbol 13 acetate 12 myristate; nucleosome; interferon-α; extracellular traps; humans; human; male; female; article; leukocyte elastase; immunofluorescence assay; neutrophil extracellular traps; citrullination; extracellular trap; high-density neutrophils; myeloproliferative neoplasia; neutrophil extracellular trap |
| Journal Title: | International Journal of Molecular Sciences |
| Volume: | 25 |
| Issue: | 24 |
| ISSN: | 1422-0067 |
| Publisher: | MDPI |
| Date Published: | 2024-12-02 |
| Start Page: | 13473 |
| Language: | English |
| DOI: | 10.3390/ijms252413473 |
| PUBMED: | 39769242 |
| PROVIDER: | scopus |
| PMCID: | PMC11677445 |
| DOI/URL: | |
| Notes: | Source: Scopus |
