Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Platelet-derived β2M regulates monocyte inflammatory responses
Zachary T. Hilt, … , Michael R. Elliott, Craig N. Morrell
Zachary T. Hilt, … , Michael R. Elliott, Craig N. Morrell
Published January 31, 2019
Citation Information: JCI Insight. 2019;4(5):e122943. https://doi.org/10.1172/jci.insight.122943.
View: Text | PDF
Research Article Vascular biology

Platelet-derived β2M regulates monocyte inflammatory responses

  • Text
  • PDF
Abstract

β-2 Microglobulin (β2M) is a molecular chaperone for the major histocompatibility class I (MHC I) complex, hemochromatosis factor protein (HFE), and the neonatal Fc receptor (FcRn), but β2M may also have less understood chaperone-independent functions. Elevated plasma β2M has a direct role in neurocognitive decline and is a risk factor for adverse cardiovascular events. β2M mRNA is present in platelets at very high levels, and β2M is part of the activated platelet releasate. In addition to their more well-studied thrombotic functions, platelets are important immune regulatory cells that release inflammatory molecules and contribute to leukocyte trafficking, activation, and differentiation. We have now found that platelet-derived β2M is a mediator of monocyte proinflammatory differentiation through noncanonical TGFβ receptor signaling. Circulating monocytes from mice lacking β2M only in platelets (Plt-β2M–/–) had a more proreparative monocyte phenotype, in part dependent on increased platelet-derived TGFβ signaling in the absence of β2M. Using a mouse myocardial infarction (MI) model, Plt-β2M–/– mice had limited post-MI proinflammatory monocyte responses and, instead, demonstrated early proreparative monocyte differentiation, profibrotic myofibroblast responses, and a rapid decline in heart function compared with WT mice. These data demonstrate a potentially novel chaperone-independent, monocyte phenotype–regulatory function for platelet β2M and that platelet-derived 2M and TGFβ have opposing roles in monocyte differentiation that may be important in tissue injury responses.

Authors

Zachary T. Hilt, Daphne N. Pariser, Sara K. Ture, Amy Mohan, Pearl Quijada, Akua A. Asante, Scott J. Cameron, Julie A. Sterling, Alyssa R. Merkel, Andrew L. Johanson, Jermaine L. Jenkins, Eric M. Small, Kathleen E. McGrath, James Palis, Michael R. Elliott, Craig N. Morrell

×

Figure 9

Plt-β2M–/– mice have an early reparative and fibrotic response to MI.

Options: View larger image (or click on image) Download as PowerPoint
Plt-β2M–/– mice have an early reparative and fibrotic response to MI.
Ca...
Cardiac mRNA was isolated from control and day-3 post-MI hearts. (A and B) Plt-β2M–/– mouse hearts had increased post-MI markers of proreparative macrophage phenotype (A) (n = 3, normalized to genotype control; **P < 0.01, 1-way ANOVA with Bonferroni correction) and increased fibroblast activation compared with WT mice (C) (n = 3, normalized to genotype control; **P < 0.01, 1-way ANOVA with Bonferroni correction).

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts