Macrophage migration inhibitory factor inhibits neutrophil apoptosis by inducing cytokine release from mononuclear cells

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Lisa Schindler¹  Leon Zwissler¹  Christine Krammer¹  Ulrike Hendgen-Cotta³  Tienush Rassaf³  Mark B. Hampton²  Nina Dickerhof²  Jürgen Bernhagen¹ 

[1] Chair of Vascular Biology, Institute for Stroke and Dementia Research ,(ISD), LMU University Hospital, Ludwig-Maximilians-University;Department of Pathology and Biomedical Science, Centre for Free Radical Research, University of Otago;Department of Cardiology and Angiology, University Hospital Essen;Munich Cluster for Systems Neurology;German Center for Cardiovascular Diseases

关键词: CXCL8;    CXCR2;    D-DT;    hypochlorous acid;    inflammation;    MIF-2;    MIF;   

DOI  :  10.1002/JLB.3A0420-242RRR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

CC BY