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Media type:
E-Article
Title:
Macrophage migration inhibitory factor inhibits neutrophil apoptosis by inducing cytokine release from mononuclear cells
Contributor:
Schindler, Lisa;
Zwissler, Leon;
Krammer, Christine;
Hendgen-Cotta, Ulrike;
Rassaf, Tienush;
Hampton, Mark B;
Dickerhof, Nina;
Bernhagen, Jürgen
imprint:
Oxford University Press (OUP), 2021
Published in:Journal of Leukocyte Biology
Language:
English
DOI:
10.1002/jlb.3a0420-242rrr
ISSN:
0741-5400;
1938-3673
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:p>The chemokine-like inflammatory cytokine macrophage migration inhibitory factor (MIF) is a pivotal driver of acute and chronic inflammatory conditions, cardiovascular disease, autoimmunity, and cancer. MIF modulates the early inflammatory response through various mechanisms, including regulation of neutrophil recruitment and fate, but the mechanisms and the role of the more recently described MIF homolog MIF-2 (D-dopachrome tautomerase; D-DT) are incompletely understood. Here, we show that both MIF and MIF-2/D-DT inhibit neutrophil apoptosis. This is not a direct effect, but involves the activation of mononuclear cells, which secrete CXCL8 and other prosurvival mediators to promote neutrophil survival. Individually, CXCL8 and MIF (or MIF-2) did not significantly inhibit neutrophil apoptosis, but in combination they elicited a synergistic response, promoting neutrophil survival even in the absence of mononuclear cells. The use of receptor-specific inhibitors provided evidence for a causal role of the noncognate MIF receptor CXCR2 expressed on both monocytes and neutrophils in MIF-mediated neutrophil survival. We suggest that the ability to inhibit neutrophil apoptosis contributes to the proinflammatory role ascribed to MIF, and propose that blocking the interaction between MIF and CXCR2 could be an important anti-inflammatory strategy in the early inflammatory response.</jats:p>