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Review
. 2019 Jun;105(6):1111-1121.
doi: 10.1002/JLB.MR0718-261RR. Epub 2019 Jan 15.

Megakaryocytes as immune cells

Pierre Cunin  1 , Peter A Nigrovic  1   2
Affiliations
Review

Megakaryocytes as immune cells

Pierre Cunin et al. J Leukoc Biol. 2019 Jun.

Abstract

Platelets play well-recognized roles in inflammation, but their cell of origin-the megakaryocyte-is not typically considered an immune lineage. Megakaryocytes are large polyploid cells most commonly identified in bone marrow. Egress via sinusoids enables migration to the pulmonary capillary bed, where elaboration of platelets can continue. Beyond receptors involved in hemostasis and thrombosis, megakaryocytes express receptors that confer immune sensing capacity, including TLRs and Fc-γ receptors. They control the proliferation of hematopoietic cells, facilitate neutrophil egress from marrow, possess the capacity to cross-present antigen, and can promote systemic inflammation through microparticles rich in IL-1. Megakaryocytes internalize other hematopoietic lineages, especially neutrophils, in an intriguing cell-in-cell interaction termed emperipolesis. Together, these observations implicate megakaryocytes as direct participants in inflammation and immunity.

Keywords: IL-1; inflammation; lung; microparticle; platelets.

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Conflict of interest statement

Conflict of Interest Disclosure

The authors declare no relevant conflict of interest.

Figures

Figure 1:
Figure 1:. Megakaryocyte development from HSC to platelet.
HSC give rise to the common myeloid progenitor (CMP), MK-erythrocyte progenitor (MEP), and the lineage-committed megakaryocyte precursor (MkP). The HSC compartment also contains stem-like MK-committed progenitors (SL-MkP), remaining quiescent at steady state but rapidly giving rise to MkP during inflammation. After multiple round of endomitosis, MkP become mature MKs and release platelets into bone marrow sinusoids or migrate to the lung vasculature, where platelet production continues through the development of proplatelets. Under acute inflammatory or cytopenic conditions, elevation of IL-1α level promotes platelet release through rapid subdivision of the MK cytoplasm into platelets (“MK rupture”). In blue: characteristic surface markers during megakaryocyte ontogeny in mouse.
Figure 2:
Figure 2:. Immunoreceptors and effector molecules in lung vs. bone marrow megakaryocytes.
A. Heat maps display examples of immune protein expression by RNAseq in MKs from lung or bone marrow. B. Values show average fragments per kilobase of transcript per million mapped reads (FPKM) across conditions. Green: chemokines; Red: cytokines and other immune effectors; Blue: immune receptors. BM, bone marrow. Figures generated from data published in Lefrancais, Ortiz-Muños, et al. (ref 8).
Figure 3:
Figure 3:. Emperipolesis in murine bone marrow and in vitro-generated megakaryocytes.
A. Asterisks show bone marrow cells internalized within MKs. H&E staining. BV: blood vessels. B. Murine MKs differentiated in vitro were co-cultured with bone marrow cells and observed by electron microscopy. Scale bars: 2μm (left images) and 500nm (right images). Nu: MK nucleus. PMN: polymorphonuclear neutrophil.
Figure 4:
Figure 4:
Megakaryocyte effector mechanisms.
See this image and copyright information in PMC

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