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Megakaryocytes contain extranuclear histones and may be a source of platelet-associated histones during sepsis

Author(s)
Frydman, Galit H.; Tessier, Shannon N.; Wong, Keith H. K.; Vanderburg, Charles R.; Fox, James G; Toner, Mehmet; Tompkins, Ronald G.; Irimia, Daniel; ... Show more Show less
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Abstract
Histones are typically located within the intracellular compartment, and more specifically, within the nucleus. When histones are located within the extracellular compartment, they change roles and become damage-associated molecular patterns (DAMPs), promoting inflammation and coagulation. Patients with sepsis have increased levels of extracellular histones, which have been shown to correlate with poor prognosis and the development of sepsis-related sequelae, such as end-organ damage. Until now, neutrophils were assumed to be the primary source of circulating histones during sepsis. In this paper, we show that megakaryocytes contain extranuclear histones and transfer histones to their platelet progeny. Upon examination of isolated platelets from patients with sepsis, we identified that patients with sepsis have increased amounts of platelet-associated histones (PAHs), which appear to be correlated with the type of infection. Taken together, these results suggest that megakaryocytes and platelets may be a source of circulating histones during sepsis and should be further explored.
Date issued
2020-03
URI
https://hdl.handle.net/1721.1/126144
Department
Massachusetts Institute of Technology. Division of Comparative Medicine; Massachusetts Institute of Technology. Department of Biological Engineering
Journal
Scientific Reports
Publisher
Springer Science and Business Media LLC
Citation
Frydman, Galit H. et al. "Megakaryocytes contain extranuclear histones and may be a source of platelet-associated histones during sepsis." Scientific Reports 10, 1 (March 2020): 4621 © 2020 The Author(s)
Version: Final published version
ISSN
2045-2322

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