Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Lung inflammatory injury and tissue repair (Jul 2023)
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model
Pathricia Veronica Tilstam, … , Günter Fingerle-Rowson, Richard Bucala
Pathricia Veronica Tilstam, … , Günter Fingerle-Rowson, Richard Bucala
Published December 1, 2021
Citation Information: J Clin Invest. 2021;131(23):e127171. https://doi.org/10.1172/JCI127171.
View: Text | PDF
Research Article Immunology Inflammation

MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model

  • Text
  • PDF
Abstract

Excessive inflammation drives the progression from sepsis to septic shock. Macrophage migration inhibitory factor (MIF) is of interest because MIF promoter polymorphisms predict mortality in different infections, and anti-MIF antibody improves survival in experimental models when administered 8 hours after infectious insult. The recent description of a second MIF superfamily member, D-dopachrome tautomerase (D-DT/MIF-2), prompted closer investigation of MIF-dependent responses. We subjected Mif–/– and Mif-2–/– mice to polymicrobial sepsis and observed a survival benefit with Mif but not Mif-2 deficiency. Survival was associated with reduced numbers of small peritoneal macrophages (SPMs) that, in contrast to large peritoneal macrophages (LPMs), were recruited into the peritoneal cavity. LPMs produced higher quantities of MIF than SPMs, but SPMs expressed higher levels of inflammatory cytokines and the MIF receptors CD74 and CXCR2. Adoptive transfer of WT SPMs into Mif–/– hosts reduced the protective effect of Mif deficiency in polymicrobial sepsis. Notably, MIF-2 lacks the pseudo-(E)LR motif present in MIF that mediates CXCR2 engagement and SPM migration, supporting a specific role for MIF in the recruitment and accumulation of inflammatory SPMs.

Authors

Pathricia Veronica Tilstam, Wibke Schulte, Thomas Holowka, Bong-Sung Kim, Jessica Nouws, Maor Sauler, Marta Piecychna, Georgios Pantouris, Elias Lolis, Lin Leng, Jürgen Bernhagen, Günter Fingerle-Rowson, Richard Bucala

×

Figure 1

MIF and MIF-2 levels increase in sepsis.

Options: View larger image (or click on image) Download as PowerPoint
MIF and MIF-2 levels increase in sepsis.
WT mice underwent CLP or sham s...
WT mice underwent CLP or sham surgery and (A) peritoneal lavage at 22 hours and (B) peripheral blood at 0, 4, 9, and 22 hours were analyzed for MIF and MIF-2 by ELISA. (A) n = 4 to 10 animals, 1-way ANOVA with Tukey’s multiple-comparison test. (B) n = 6 to 22 animals, 2-way ANOVA with Bonferroni’s multiple-comparison test. *P < 0.05; **P < 0.01; ****P < 0.0001.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts