Megakaryocytes respond during sepsis and display innate immune cell behaviors

Megakaryocytes (MKs) are precursors to platelets, the second most abundant cells in the peripheral circulation. However, while platelets are known to participate in immune responses and play significant functions during infections, the role of MKs within the immune system remains largely unexplored....

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Main Authors: Galit H. Frydman, Felix Ellett, Julianne Jorgensen, Anika L. Marand, Lawrence Zukerberg, Martin K. Selig, Shannon N. Tessier, Keith H. K. Wong, David Olaleye, Charles R. Vanderburg, James G. Fox, Ronald G. Tompkins, Daniel Irimia
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1083339/full
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author Galit H. Frydman
Galit H. Frydman
Felix Ellett
Julianne Jorgensen
Anika L. Marand
Lawrence Zukerberg
Martin K. Selig
Shannon N. Tessier
Keith H. K. Wong
David Olaleye
Charles R. Vanderburg
James G. Fox
Ronald G. Tompkins
Daniel Irimia
author_facet Galit H. Frydman
Galit H. Frydman
Felix Ellett
Julianne Jorgensen
Anika L. Marand
Lawrence Zukerberg
Martin K. Selig
Shannon N. Tessier
Keith H. K. Wong
David Olaleye
Charles R. Vanderburg
James G. Fox
Ronald G. Tompkins
Daniel Irimia
author_sort Galit H. Frydman
collection DOAJ
description Megakaryocytes (MKs) are precursors to platelets, the second most abundant cells in the peripheral circulation. However, while platelets are known to participate in immune responses and play significant functions during infections, the role of MKs within the immune system remains largely unexplored. Histological studies of sepsis patients identified increased nucleated CD61+ cells (MKs) in the lungs, and CD61+ staining (likely platelets within microthrombi) in the kidneys, which correlated with the development of organ dysfunction. Detailed imaging cytometry of peripheral blood from patients with sepsis found significantly higher MK counts, which we predict would likely be misclassified by automated hematology analyzers as leukocytes. Utilizing in vitro techniques, we show that both stem cell derived MKs (SC MKs) and cells from the human megakaryoblastic leukemia cell line, Meg-01, undergo chemotaxis, interact with bacteria, and are capable of releasing chromatin webs in response to various pathogenic stimuli. Together, our observations suggest that MK cells display some basic innate immune cell behaviors and may actively respond and play functional roles in the pathophysiology of sepsis.
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spelling doaj.art-b06f5c29384149ba997a482d680212382023-03-02T07:10:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.10833391083339Megakaryocytes respond during sepsis and display innate immune cell behaviorsGalit H. Frydman0Galit H. Frydman1Felix Ellett2Julianne Jorgensen3Anika L. Marand4Lawrence Zukerberg5Martin K. Selig6Shannon N. Tessier7Keith H. K. Wong8David Olaleye9Charles R. Vanderburg10James G. Fox11Ronald G. Tompkins12Daniel Irimia13Division of Comparative Medicine and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United StatesBioMEMS Resource Center and Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, United StatesBioMEMS Resource Center and Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, United StatesBioMEMS Resource Center and Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, United StatesBioMEMS Resource Center and Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, United StatesDepartment of Pathology, Massachusetts General Hospital, Boston, MA, United StatesDepartment of Pathology, Massachusetts General Hospital, Boston, MA, United StatesBioMEMS Resource Center and Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, United StatesBioMEMS Resource Center and Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, United StatesDivision of Comparative Medicine and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United StatesHarvard Neurodiscovery Center, Harvard Medical School, Boston, MA, United StatesDivision of Comparative Medicine and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United StatesBioMEMS Resource Center and Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, United StatesBioMEMS Resource Center and Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, United StatesMegakaryocytes (MKs) are precursors to platelets, the second most abundant cells in the peripheral circulation. However, while platelets are known to participate in immune responses and play significant functions during infections, the role of MKs within the immune system remains largely unexplored. Histological studies of sepsis patients identified increased nucleated CD61+ cells (MKs) in the lungs, and CD61+ staining (likely platelets within microthrombi) in the kidneys, which correlated with the development of organ dysfunction. Detailed imaging cytometry of peripheral blood from patients with sepsis found significantly higher MK counts, which we predict would likely be misclassified by automated hematology analyzers as leukocytes. Utilizing in vitro techniques, we show that both stem cell derived MKs (SC MKs) and cells from the human megakaryoblastic leukemia cell line, Meg-01, undergo chemotaxis, interact with bacteria, and are capable of releasing chromatin webs in response to various pathogenic stimuli. Together, our observations suggest that MK cells display some basic innate immune cell behaviors and may actively respond and play functional roles in the pathophysiology of sepsis.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1083339/fullmegakaryocyteplateletsepsisinnateinfectious
spellingShingle Galit H. Frydman
Galit H. Frydman
Felix Ellett
Julianne Jorgensen
Anika L. Marand
Lawrence Zukerberg
Martin K. Selig
Shannon N. Tessier
Keith H. K. Wong
David Olaleye
Charles R. Vanderburg
James G. Fox
Ronald G. Tompkins
Daniel Irimia
Megakaryocytes respond during sepsis and display innate immune cell behaviors
Frontiers in Immunology
megakaryocyte
platelet
sepsis
innate
infectious
title Megakaryocytes respond during sepsis and display innate immune cell behaviors
title_full Megakaryocytes respond during sepsis and display innate immune cell behaviors
title_fullStr Megakaryocytes respond during sepsis and display innate immune cell behaviors
title_full_unstemmed Megakaryocytes respond during sepsis and display innate immune cell behaviors
title_short Megakaryocytes respond during sepsis and display innate immune cell behaviors
title_sort megakaryocytes respond during sepsis and display innate immune cell behaviors
topic megakaryocyte
platelet
sepsis
innate
infectious
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1083339/full
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