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
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact

Citations to this article

Plasmin drives burn-induced systemic inflammatory response syndrome
Breanne H. Y. Gibson, … , Timothy S. Blackwell, Jonathan G. Schoenecker
Breanne H. Y. Gibson, … , Timothy S. Blackwell, Jonathan G. Schoenecker
Published December 8, 2021
Citation Information: JCI Insight. 2021;6(23):e154439. https://doi.org/10.1172/jci.insight.154439.
View: Text | PDF
Research Article Inflammation

Plasmin drives burn-induced systemic inflammatory response syndrome

  • Text
  • PDF
Abstract

Severe injuries, such as burns, provoke a systemic inflammatory response syndrome (SIRS) that imposes pathology on all organs. Simultaneously, severe injury also elicits activation of the fibrinolytic protease plasmin. While the principal adverse outcome of plasmin activation in severe injury is compromised hemostasis, plasmin also possesses proinflammatory properties. We hypothesized that, following a severe injury, early activation of plasmin drives SIRS. Plasmin activation was measured and related to injury severity, SIRS, coagulopathy, and outcomes prospectively in burn patients who are not at risk of hemorrhage. Patients exhibited early, significant activation of plasmin that correlated with burn severity, cytokines, coagulopathy, and death. Burn with a concomitant, remote muscle injury was employed in mice to determine the role of plasmin in the cytokine storm and inflammatory cascades in injured tissue distant from the burn injury. Genetic and pharmacologic inhibition of plasmin reduced the burn-induced cytokine storm and inflammatory signaling in injured tissue. These findings demonstrate (a) that severe injury–induced plasmin activation is a key pathologic component of the SIRS-driven cytokine storm and SIRS-activated inflammatory cascades in tissues distant from the inciting injury and (b) that targeted inhibition of plasmin activation may be effective for limiting both hemorrhage and tissue-damaging inflammation following injury.

Authors

Breanne H. Y. Gibson, Colby C. Wollenman, Stephanie N. Moore-Lotridge, Patrick R. Keller, J. Blair Summitt, Alexey R. Revenko, Matthew J. Flick, Timothy S. Blackwell, Jonathan G. Schoenecker

×

Loading citation information...
Advertisement

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts