Journal ArticleDOI
MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment
Jürgen Bernhagen,Regina M. Krohn,Hongqi Lue,Julia L. Gregory,Alma Zernecke,Rory R. Koenen,Manfred Dewor,Ivan T. Georgiev,Andreas Schober,Lin Leng,Teake Kooistra,Gunter Fingerle-Rowson,Pietro Ghezzi,Robert Kleemann,Shaun R. McColl,Richard Bucala,Michael J. Hickey,Christian Weber +17 more
TLDR
Targeting MIF in individuals with manifest atherosclerosis can potentially be used to treat this condition and displays chemokine-like functions and acts as a major regulator of inflammatory cell recruitment and atherogenesis.Abstract:
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 G αi- 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 complex, and monocyte arrest elicited by MIF in inflamed or atherosclerotic arteries involved both CXCR2 and CD74. In vivo, Mif deficiency impaired monocyte adhesion to the arterial wall in atherosclerosis-prone mice, and MIF-induced leukocyte recruitment required Il8rb (which encodes Cxcr2). Blockade of Mif but not of canonical ligands of Cxcr2 or Cxcr4 in mice with advanced atherosclerosis led to plaque regression and reduced monocyte and T-cell content in plaques. By activating both CXCR2 and CXCR4, MIF displays chemokine-like functions and acts as a major regulator of inflammatory cell recruitment and atherogenesis. Targeting MIF in individuals with manifest atherosclerosis can potentially be used to treat this condition. © 2007 Nature Publishing Group.read more
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Patent
Methods of treating inflammation
TL;DR: In this paper, the peptides for use in inhibiting the interactions of PF4 and RANTES are presented for treating an inflammatory disease, disorder, condition, or symptom.
Journal ArticleDOI
Changes in the peripheral blood and bone marrow from untreated advanced breast cancer patients that are associated with the establishment of bone metastases
Leandro Marcelo Martinez,Valeria Beatriz Fernández Vallone,Vivian Labovsky,Hosoon Choi,Erica Leonor Hofer,Leonardo Feldman,Raul H. Bordenave,Emilio Batagelj,Federico Dimase,Ana Rodriguez Villafañe,Norma Alejandra Chasseing +10 more
TL;DR: Results can reveal new information about what alterations happen in the bone marrow of advanced breast cancer patients before bone colonisation, changes that create optimal soil for the metastatic cascade progression.
Journal ArticleDOI
Understanding microscopic binding of macrophage migration inhibitory factor with phenolic hydrazones by molecular docking, molecular dynamics simulations and free energy calculations
TL;DR: The results suggest that the flexibility of MIF is essential in ligand binding process and the essential factors for MIF-inhibitor interactions derived from the theoretical predictions are useful for designing potent inhibitors of Mif.
Journal ArticleDOI
Expression of Human Tissue Factor Pathway Inhibitor on Vascular Smooth Muscle Cells Inhibits Secretion of Macrophage Migration Inhibitory Factor and Attenuates Atherosclerosis in ApoE−/− Mice
Daxin Chen,Min Xia,C Hayford,El Li Tham,Vikki Semik,Stuart Hurst,Ying Chen,Henry H. Tam,Jun Pan,Yucheng Wang,Xiaojin Tan,Hui-Yao Lan,Huahao Shen,Vijay V. Kakkar,Qingbo Xu,John H. McVey,Anthony Dorling +16 more
TL;DR: The data indicate that tissue factor plays a hitherto unreported role in the generation of MIF by SMCs in Atherosclerosis-prone ApoE−/− mice, inhibition of which significantly prevents the development of atherosclerosis, through inhibition of leukocyte recruitment.
Journal ArticleDOI
Blood Levels of Macrophage Migration Inhibitory Factor after Successful Resuscitation from Cardiac Arrest
Christian Stoppe,Michael Fries,Rolf Rossaint,Gerrit Grieb,Mark Coburn,David Simons,David Brücken,Jürgen Bernhagen,Norbert Pallua,Steffen Rex +9 more
TL;DR: MIF shows a rapid and pronounced increase following CPR, hence allowing a very early assessment of the inflammatory response and further studies are warranted in larger patient groups to determine the prognostic significance of MIF.
References
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Journal ArticleDOI
The Many Roles of Chemokines and Chemokine Receptors in Inflammation
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