MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model

Tilstam, Pathricia V.; 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

doi:10.1172/jci127171

Cited by 40 publications

(44 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies have shown that after LPS stimulated macrophages, rapamycin target protein, and hypoxia inducible factor-1 α (hypoxia-inducible factor-1 α , HIF-1 α ). Increased expression can promote the expression of glycolysis-related genes and increase the expression of fructose-2-kinase 6-phosphate, thereby promoting aerobic glycolysis [ 18 ]. After LPS activated macrophages, the expression of inducible nitric oxide synthase increased, and the activity of some target proteins in mitochondrial electron transport chain.…”

Section: Changes Of Macrophages In Sepsismentioning

confidence: 99%

Ferroptosis in Macrophage Impairment in Sepsis

Liu

2022

Applied Bionics and Biomechanics

View full text Add to dashboard Cite

Sepsis is a clinical syndrome with high mortality, which can lead to multiple organ dysfunction syndrome. Nonspecific immune dysfunction and immune imbalance are its important pathological features. Macrophages are important immune cells and one of the important components of innate and adaptive immunity. Regulating the function of macrophages may be a potential method for the treatment of sepsis. Up to now, ferroptosis has been proved to be involved in the pathophysiological mechanism of many diseases, such as Alzheimer’s disease, cancer, Parkinson’s disease, and renal degeneration. At present, relevant studies have reported that ferroptosis may be involved in the occurrence of sepsis This paper reviews the existing mechanisms of iron ptosis in macrophages in sepsis, with a view to providing si’l for future studies on sepsis.

show abstract

Section: Changes Of Macrophages In Sepsismentioning

confidence: 99%

Ferroptosis in Macrophage Impairment in Sepsis

Liu

2022

Applied Bionics and Biomechanics

View full text Add to dashboard Cite

show abstract

“…We found that MIF-(CD44-CD74) pairs mediated signaling from CD4 + T cells and CD8 + T cells to macrophage-like VSMCs. On the other hand, MIF-(CD74 + CXCR4) mediated signal transmission from contractile VSMCs, T-cell-like VSMCs, and macrophage-like VSMCs to B cells Numerous studies have shown that MIF possesses the function of recruiting and activating macrophages through combining with CD74 and CXCR2 (24)(25)(26) and promote normal cells to acquire an inflammatory phenotype by interacting with the receptor CD74 (27). MIF binds to CD74 + CXCR4, which promotes B-cell migration (28).…”

Section: Discussionmentioning

confidence: 99%

Deciphering the Intercellular Communication Between Immune Cells and Altered Vascular Smooth Muscle Cell Phenotypes in Aortic Aneurysm From Single-Cell Transcriptome Data

Cao

Zhengchao

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

BackgroundVascular smooth muscle cell (VSMC) phenotype switching has been preliminarily found in aortic aneurysms. However, two major questions were raised: (1) What factors drive phenotypic switching of VSMCs in aortic aneurysms? (2) What role does VSMC phenotype transformation play in aortic aneurysms? We speculated that the interaction between infiltrated immune cells and VSMCs played a pivotal role in aortic aneurysm expansion.Materials and MethodsWe obtained single-cell transcriptome data GSE155468 that incorporate eight aortic aneurysm samples and three normal aorta samples. A standard single-cell analysis procedure was performed by Seurat (v3.1.2) for identifying the general cell components. Subsequently, VSMCs were extracted separately and re-clustered for identifying switched VSMC phenotypes. VSMC phenotype annotation was relied on the definitions of specific VSMC phenotypes in published articles. Vital VSMC phenotypes were validated by immunofluorescence. Next, identified immune cells and annotated vital VSMC phenotypes were extracted for analyzing the intercellular communication. R package CellChat (v1.1.3) was used for investigating the communication strength, signaling pathways, and communication patterns between various VSMC phenotypes and immune cells.ResultA total of 42,611 cells were identified as CD4 + T cells, CD8 + T cells, VSMC, monocytes, macrophages, fibroblasts, endothelial cells, and B cells. VSMCs were further classified into contractile VSMCs, secreting VSMCs, macrophage-like VSMCs, mesenchymal-like VSMCs, adipocyte-like VSMCs, and T-cell-like VSMCs. Intercellular communication analysis was performed between immune cells (macrophages, B cells, CD4 + T cells, CD8 + T cells) and immune related VSMCs (macrophage-like VSMCs, mesenchymal-like VSMCs, T-cell-like VSMCs, contractile VSMCs). Among selected cell populations, 27 significant signaling pathways with 61 ligand–receptor pairs were identified. Macrophages and macrophage-like VSMCs both assume the roles of a signaling sender and receiver, showing the highest communication capability. T cells acted more as senders, while B cells acted as receivers in the communication network. T-cell-like VSMCs and contractile VSMCs were used as senders, while mesenchymal-like VSMCs played a poor role in the communication network. Signaling macrophage migration inhibitory factor (MIF), galectin, and C-X-C motif chemokine ligand (CXCL) showed high information flow of intercellular communication, while signaling complement and chemerin were completely turned on in aortic aneurysms. MIF and galectin promoted VSMC switch into macrophage-like phenotypes, CXCL, and galectin promoted VSMCs transform into T-cell-like phenotypes. MIF, galectin, CXCL, complement, and chemerin all mediated the migration and recruitment of immune cells into aortic aneurysms.ConclusionThe sophisticated intercellular communication network existed between immune cells and immune-related VSMCs and changed as the aortic aneurysm progressed. Signaling MIF, galectin, CXCL, chemerin, and complement made a significant contribution to aortic aneurysm progression through activating immune cells and promoting immune cell migration, which could serve as the potential target for the treatment of aortic aneurysms.

show abstract

“…88 In contrast, Rajasekaran and colleagues found that MIF-2 promotes the recruitment of neutrophils into inflamed lungs. 105 While the role of CXCR2, an established neutrophil recruitment chemokine receptor, was not specifically explored in that study, the observed lack of involvement of CXCR2 in the macrophage recruitment experiments of Tilstam et al 88 may suggest that MIF-2mediated neutrophil recruitment may be supported by a CD74 and/or CXCR4 mechanism, or via an indirect mechanism, as implicated by Schindler et al, who obtained evidence for monocyte/macrophage-neutrophil crosstalk. 103 Winner et al revealed a covalent modification at the Nterminal proline of both MIF-2 and MIF by 4-IPP, which leads to the production of 6-phenylpyrimidine (6-PP) adduct.…”

Section: Mif-2 In Acute Inflammation Sepsis and Covid-19 And Comparis...mentioning

confidence: 95%

“…58 At the same time, chemotactic effects elicited by MIF-2 are unlikely to involve CXCR2 engagement. 88 Morphometric plaque analysis suggests that Mif-2 knockout mice exhibit reduced lesions and plaque macrophage counts in both early and advanced stages of atherosclerosis. The latter also implies that MIF-2-elicited lesional leukocyte recruitment promotes atherogenesis.…”

Section: Role Of Mif-2 In Heart Failure and Comparison To Mifmentioning

confidence: 99%

“…81 Similarly, while the release pathway of MIF has been amply characterized to follow an unconventional secretion mechanism involving the NLRP3 inflammasome, ATP-binding cassette transporters and/or gasdermin-like pores as well as the Golgiassociated protein p115, [82][83][84][85][86][87] virtually nothing is known about the secretion mechanism of MIF-2, except that it is promoted by inflammatory and hypoxic conditions and cancerogenic cell stress. 46,53,88 The studies on MIF-2 from rat liver and later on from red blood cells also led to its initial biochemical characterization and determination of a molecular weight of about 12 kDa for its monomeric form. 89 MIF-2 has no similarities to any other enzymes that catalyze the conversion of Ldopachrome into DHICA during melanin biosynthesis, nor to D-amino acid oxidase 90 or the L-dopachrome tautomerases tyrosine-related proteins TRP-1 and TRP-2.…”

Section: Origin Tautomerase Activity and Structural Characteristics O...mentioning

confidence: 99%

See 1 more Smart Citation

D‐dopachrome tautomerase in cardiovascular and inflammatory diseases—A new kid on the block or just another MIF?

et al. 2022

Self Cite

View full text Add to dashboard Cite

Macrophage migration inhibitory factor (MIF) as well as its more recently described structural homolog D‐dopachrome tautomerase (D‐DT), now also termed MIF‐2, are atypical cytokines and chemokines with key roles in host immunity. They also have an important pathogenic role in acute and chronic inflammatory conditions, cardiovascular diseases, lung diseases, adipose tissue inflammation, and cancer. Although our mechanistic understanding of MIF‐2 is relatively limited compared to the extensive body of evidence available for MIF, emerging data suggests that MIF‐2 is not only a functional phenocopy of MIF, but may have differential or even oppositional activities, depending on the disease and context. In this review, we summarize and discuss the similarities and differences between MIF and MIF‐2, with a focus on their structures, receptors, signaling pathways, and their roles in diseases. While mainly covering the roles of the MIF homologs in cardiovascular, inflammatory, autoimmune, and metabolic diseases, we also discuss their involvement in cancer, sepsis, and chronic obstructive lung disease (COPD). A particular emphasis is laid upon potential mechanistic explanations for synergistic or cooperative activities of the MIF homologs in cancer, myocardial diseases, and COPD as opposed to emerging disparate or antagonistic activities in adipose tissue inflammation, metabolic diseases, and atherosclerosis. Lastly, we discuss potential future opportunities of jointly targeting MIF and MIF‐2 in certain diseases, whereas precision targeting of only one homolog might be preferable in other conditions. Together, this article provides an update of the mechanisms and future therapeutic avenues of human MIF proteins with a focus on their emerging, surprisingly disparate activities, suggesting that MIF‐2 displays a variety of activities that are distinct from those of MIF.

show abstract

MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model

Abstract: Authorship note: PVT and WS contributed equally to this work. Conflict of interest: RB and JB are listed as co-inventors on issued patents (US20120149044A1 and US20100267714A1) for MIF antagonists.

Cited by 40 publications

References 59 publications

Ferroptosis in Macrophage Impairment in Sepsis

Ferroptosis in Macrophage Impairment in Sepsis

Deciphering the Intercellular Communication Between Immune Cells and Altered Vascular Smooth Muscle Cell Phenotypes in Aortic Aneurysm From Single-Cell Transcriptome Data

D‐dopachrome tautomerase in cardiovascular and inflammatory diseases—A new kid on the block or just another MIF?

Contact Info

Product

Resources

About