Tilstam, Pathricia Veronica, Schulte, Wibke, Holowka, Thomas, Kim, Bong-Sung, Nouws, Jessica, Sauler, Maor ORCID: 0000-0001-5240-7978, Piecychna, Marta, Pantouris, Georgios ORCID: 0000-0001-5547-1406, Lolis, Elias, Leng, Lin ORCID: 0000-0002-0605-358X, Bernhagen, Juergen, Fingerle-Rowson, Guenter and Bucala, Richard (2021). MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model. J. Clin. Invest., 131 (23). ANN ARBOR: AMER SOC CLINICAL INVESTIGATION INC. ISSN 1558-8238

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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-dopachrometautomerase (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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Tilstam, Pathricia VeronicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulte, WibkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holowka, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kim, Bong-SungUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nouws, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sauler, MaorUNSPECIFIEDorcid.org/0000-0001-5240-7978UNSPECIFIED
Piecychna, MartaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pantouris, GeorgiosUNSPECIFIEDorcid.org/0000-0001-5547-1406UNSPECIFIED
Lolis, EliasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leng, LinUNSPECIFIEDorcid.org/0000-0002-0605-358XUNSPECIFIED
Bernhagen, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fingerle-Rowson, GuenterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bucala, RichardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-600615
DOI: 10.1172/JCI127171
Journal or Publication Title: J. Clin. Invest.
Volume: 131
Number: 23
Date: 2021
Publisher: AMER SOC CLINICAL INVESTIGATION INC
Place of Publication: ANN ARBOR
ISSN: 1558-8238
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MIGRATION-INHIBITORY-FACTOR; SEPTIC SHOCK; FUNCTIONAL POLYMORPHISMS; CRITICAL MEDIATOR; REGULATORY ROLE; CYTOKINE; PREDICTORS; MORTALITY; RESPONSES; TRIALMultiple languages
Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60061

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