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MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model.
Tilstam, Pathricia Veronica; Schulte, Wibke; Holowka, Thomas; Kim, Bong-Sung; Nouws, Jessica; Sauler, Maor; Piecychna, Marta; Pantouris, Georgios; Lolis, Elias; Leng, Lin; Bernhagen, Jürgen; Fingerle-Rowson, Günter; Bucala, Richard.
Afiliação
  • Tilstam PV; Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Schulte W; Department of Immunology, Harvard Medical School, Boston, Massachusetts, USA.
  • Holowka T; Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Kim BS; Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Nouws J; Department of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Sauler M; Berlin Institute of Health (BIH), Berlin, Germany.
  • Piecychna M; Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Pantouris G; Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Lolis E; Department of Plastic, Reconstructive and Hand Surgery, RWTH Aachen University, Aachen, Germany.
  • Leng L; Division of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland.
  • Bernhagen J; Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Fingerle-Rowson G; Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Bucala R; Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
J Clin Invest ; 131(23)2021 12 01.
Article em En | MEDLINE | ID: mdl-34850744
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fatores Inibidores da Migração de Macrófagos / Sepse / Oxirredutases Intramoleculares / Inflamação Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fatores Inibidores da Migração de Macrófagos / Sepse / Oxirredutases Intramoleculares / Inflamação Idioma: En Ano de publicação: 2021 Tipo de documento: Article