ArticleProceedings of the National Academy of Sciences of the United States of America2008
Structural determinants of MIF functions in CXCR2-mediated inflammatory and atherogenic leukocyte recruitment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 174 citations in OpenAlex.
- Helminth proteins recapitulate key structural motifs of MIF to facilitate immunomodulation of host receptors.iScience · 2026Article
- Oxidized MIF is an Alzheimer's disease drug target relaying external risk factors to tau pathology.Cell reports. Medicine · 2026Article
- Macrophage migration inhibitory factor (MIF): a Janus-faced cytokine in viral pathogenesis and host defense.Immunologic research · 2025Review
- The multifaced role of the macrophage migration inhibitory factor family in organ fibrosis.American journal of physiology. Cell physiology · 2025Review
- An atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis.Nature communications · 2025Article
- Top-Down Stability of Proteins from Rates of Oxidation (TD-SPROX) Approach for Measuring Proteoform-Specific Folding Stability.Analytical chemistry · 2024Article
- Article
- A genome-wide association study of neutrophil count in individuals associated to an African continental ancestry group facilitates studies of malaria pathogenesis.Human genomics · 2024Article
- Highly Selective MIF Ketonase Inhibitor KRP-6 Diminishes M1 Macrophage Polarization and Metabolic Reprogramming.Antioxidants (Basel, Switzerland) · 2023Article
- Allosteric Inhibitors of Macrophage Migration Inhibitory Factor (MIF) Interfere with Apoptosis-Inducing Factor (AIF) Co-Localization to Prevent Parthanatos.Journal of medicinal chemistry · 2023Article
- Macrophage migration inhibitory factor receptor CD74 expression is associated with expansion and differentiation of effector T cells in COVID-19 patients.Frontiers in immunology · 2023Article
- Prevention by the CXCR2 antagonist SCH527123 of the calcification of porcine heart valve cusps implanted subcutaneously in rats.Frontiers in cardiovascular medicine · 2023Article
- Heterocomplexes between the atypical chemokine MIF and the CXC-motif chemokine CXCL4L1 regulate inflammation and thrombus formation.Cellular and molecular life sciences : CMLS · 2022Article
- Single-cell RNA landscape of cell fate decision of renal proximal tubular epithelial cells and immune-microenvironment in kidney fibrosis.Clinical and translational medicine · 2022Article
- Thieno[2,3-Journal of medicinal chemistry · 2022Article
- Macrophage migration inhibitory factor family proteins are multitasking cytokines in tissue injury.Cellular and molecular life sciences : CMLS · 2022Review
- The role of CD74 in cardiovascular disease.Frontiers in cardiovascular medicine · 2022Review
- The Role of MIF and IL-10 as Molecular Yin-Yang in the Modulation of the Host Immune Microenvironment During Infections: African Trypanosome Infections as a Paradigm.Frontiers in immunology · 2022Review
- A Cysteine Variant at an Allosteric Site Alters MIF Dynamics and Biological Function in Homo- and Heterotrimeric Assemblies.Frontiers in molecular biosciences · 2022Article
- MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model.The Journal of clinical investigation · 2021Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have recently identified the archaic cytokine macrophage migration inhibitory factor (MIF) as a non-canonical ligand of the CXC chemokine receptors CXCR2 and CXCR4 in inflammatory and atherogenic cell recruitment. Because its affinity for CXCR2 was particularly high, we hypothesized that MIF may feature structural motives shared by canonical CXCR2 ligands, namely the conserved N-terminal Glu-Leu-Arg (ELR) motif. Sequence alignment and structural modeling indeed revealed a pseudo-(E)LR motif (Asp-44-X-Arg-11) constituted by non-adjacent residues in neighboring loops but with identical parallel spacing as in the authentic ELR motif. Structure-function analysis demonstrated that mutation of residues R11, D44, or both preserve proper folding and the intrinsic catalytic property of MIF but severely compromises its binding to CXCR2 and abrogates MIF/CXCR2-mediated functions in chemotaxis and arrest of monocytes on endothelium under flow conditions. R11A-MIF and the R11A/D44A-MIF double-mutant exhibited a pronounced defect in triggering leukocyte recruitment to early atherosclerotic endothelium in carotid arteries perfused ex vivo and upon application in a peritonitis model. The function of D44A-MIF in peritoneal leukocyte recruitment was preserved as a result of compensatory use of CXCR4. In conjunction, our data identify a pseudo-(E)LR motif as the structural determinant for MIF's activity as a non-canonical CXCR2 ligand, epitomizing the structural resemblance of chemokine-like ligands with chemokines and enabling selective targeting of pro-inflammatory MIF/CXCR2 interactions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.