MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment

@article{Bernhagen2007MIFIA,
  title={MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment},
  author={J{\"u}rgen Bernhagen and Regina M. Krohn and Hongqi Lue and Julia L. Gregory and Alma Zernecke and Rory R. Koenen and Manfred Dewor and Ivan T. Georgiev and Andreas Schober and Lin Leng and Teake Kooistra and G{\"u}nter Fingerle-Rowson and Pietro Ghezzi and Robert Kleemann and Shaun R. McColl and Richard J. Bucala and Michael J. Hickey and Christian Weber},
  journal={Nature Medicine},
  year={2007},
  volume={13},
  pages={587-596}
}
The cytokine macrophage migration inhibitory factor (MIF) plays a critical role in inflammatory diseases and atherogenesis. We identify the chemokine receptors CXCR2 and CXCR4 as functional receptors for MIF. MIF triggered Gαi- and integrin-dependent arrest and chemotaxis of monocytes and T cells, rapid integrin activation and calcium influx through CXCR2 or CXCR4. MIF competed with cognate ligands for CXCR4 and CXCR2 binding, and directly bound to CXCR2. CXCR2 and CD74 formed a receptor… 
Inflammatory diseases: MIF's receptors revealed
  • C. Harrison
  • Biology, Medicine
    Nature Reviews Drug Discovery
  • 2007
TLDR
By activating both CXCR2 and CX CR4, MIF displays chemokine-like functions and acts as a regulator of inflammatory cell recruitment and atherogenesis and, therefore, targeting MIF could represent a new strategy to treat atherosclerosis.
Arrest Functions of the MIF Ligand/Receptor Axes in Atherogenesis
TLDR
MIF was originally identified as macrophage migration inhibitory factor, but is now known as a potent inflammatory cytokine with CLFs including chemotaxis and leukocyte arrest, and the structural similarities between MIF and the bona fide CXCR2 ligand CXCL8 are discussed while emphasized.
Chemokine-like functions of MIF in atherosclerosis
TLDR
MIF has been identified as an important regulator of atherosclerotic vascular disease with exceptional chemokine-like functions and detailed analysis of the interaction of MIF with its receptors could provide valuable information for drug development for the anti-inflammatory treatment of established and unstable atherosclerosis.
Macrophage Migration Inhibitory Factor-CXCR4 Receptor Interactions
TLDR
Novel molecular information is provided about the structural elements that govern the interaction between MIF and CXCR4 that identify similarities with classical chemokine-receptor interactions but also provide evidence for a partial allosteric agonist compared with CXCL12 that is possible due to the two binding sites of CX CR4.
ZAP-70 the Receptors CXCR4 and CD74 and MIF Promotes B Cell Chemotaxis through
TLDR
The model proposes that MIF promotes B cell chemotaxis through cooperative action of the receptors CXCR4 and CD74, and proposes novel pathways of MIF/MIF receptor–mediated B cell migration responses that could have important implications for various disease settings.
MIF Promotes B Cell Chemotaxis through the Receptors CXCR4 and CD74 and ZAP-70 Signaling
TLDR
It is concluded that MIF promotes the migration of B cells through a ZAP-70–dependent pathway mediated by cooperative engagement of CXCR4 and CD74, and suggest that Mif may contribute to B cell recruitment in vivo.
Structural determinants of MIF functions in CXCR2-mediated inflammatory and atherogenic leukocyte recruitment
TLDR
A pseudo-(E)LR motif is identified as the structural determinant for MIF's activity as a non-canonical CX CR2 ligand, epitomizing the structural resemblance of chemokine-like ligands with chemokines and enabling selective targeting of pro-inflammatory MIF/CXCR2 interactions.
A MIF‐Derived Cyclopeptide that Inhibits MIF Binding and Atherogenic Signaling via the Chemokine Receptor CXCR2
TLDR
MIF(cyclo10), a designed cyclized variant of MIF(47–56), inhibited key inflammatory and atherogenic MIF activities and exhibited strongly improved resistance to proteolytic degradation in human plasma in vitro, thus suggesting that it could serve as a promising basis for MIF‐derived anti‐atherosclerotic peptides.
MIF interacts with CXCR7 to promote receptor internalization, ERK1/2 and ZAP‐70 signaling, and lymphocyte chemotaxis
TLDR
B cells from Cxcr7‐/‐ mice exhibited an ablated transmigration response to MIF, indicating that CXCR7 is essential for MIF‐promoted B‐cell migration, and suggest a functional role of the M IF‐CX CR7 axis in B‐lymphocyte migration.
Diversity and Inter-Connections in the CXCR4 Chemokine Receptor/Ligand Family: Molecular Perspectives
TLDR
Insight is provided into the diversity and inter-connections in the CXCR4 receptor/ligand family and the atypical chemokine macrophage migration inhibitory factor (MIF) was identified as an alternative, non-cognate ligand for CxCR4 and shown to mediate chemotaxis and arrest of CX CR4-expressing T-cells.
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