Understanding the complex chromatin dynamics in primary human neutrophils during PMA-induced NET formation.
| Autor: | Atteberry B; Innovation Laboratory, Volition America, Carlsbad, CA, United States., Berman BP; Innovation Laboratory, Volition America, Carlsbad, CA, United States.; Department of Developmental Biology and Cancer Research, The Hebrew University of Jerusalem, Jerusalem, Israel., Kelly TK; Innovation Laboratory, Volition America, Carlsbad, CA, United States., Cayford J; Innovation Laboratory, Volition America, Carlsbad, CA, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in immunology [Front Immunol] 2024 Oct 25; Vol. 15, pp. 1445638. Date of Electronic Publication: 2024 Oct 25 (Print Publication: 2024). |
| DOI: | 10.3389/fimmu.2024.1445638 |
| Abstrakt: | Background: Primary human neutrophils play a pivotal role in innate immunity, mainly through the formation of neutrophil extracellular traps (NETs) in a process known as NETosis. This cell-death pathway is crucial for combating infections but is also implicated in many inflammatory diseases, such as sepsis, systemic lupus erythematosus, and rheumatoid arthritis. Methods: The study presented here investigates chromatin dynamics during NET formation by stimulating primary human neutrophils with phorbol 12-myristate 13-acetate (PMA). We adapt the ATAC-Seq (assay for transposase-accessible chromatin using sequencing) method to isolated neutrophils and characterize a time-dependent chromatin response. Results: We found that chromatin accessibility patterns are consistent across individual donors and most chromatin changes occur within 30 min, with many continuing across the 90 min assessed in this study. Regulatory regions gaining accessibility were associated with the activity of pathways that have been implicated in NOX-dependent NET formation. Conclusions: Our findings increase the understanding of the chromatin changes underlying NET formation and also identify potential early-acting targets for modulating this process in inflammatory diseases. Competing Interests: All authors are employees or contractors for VolitionRx. BA, JC, BB, and TK hold stock in VolitionRx. (Copyright © 2024 Atteberry, Berman, Kelly and Cayford.) |
| Databáze: | MEDLINE |
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