title: Chemokine-like functions of MIF in atherosclerosis.
abstract: The cytokine macrophage migration inhibitory factor (MIF) is a unique pro-inflammatory regulator of many acute and chronic inflammatory diseases. In the pathogenesis of atherosclerosis, chronic inflammation of the arterial wall characterized by chemokine-mediated influx of leukocytes plays a central role. The contribution of MIF to atherosclerotic vascular disease has come into focus of many studies in recent years. MIF is highly expressed in macrophages and endothelial cells of different types of atherosclerotic plaques, and functional studies established the contribution of MIF to lesion progression and plaque inflammation. This proatherogenic effect may partly be explained by the finding that MIF regulates inflammatory cell recruitment to lesion areas. Similar to chemokines, MIF induces integrin-dependent arrest and transmigration of monocytes and T cells. These chemokine-like functions are mediated through interaction of MIF with the chemokine receptors CXCR2 and CXCR4 as a non-canonical ligand. In atherogenic monocyte recruitment, MIF-induced monocyte adhesion involves CD74 and CXCR2, which form a signaling receptor complex. In addition to lesion progression, MIF has been implicated in plaque destabilization, since MIF is predominantly expressed in vulnerable plaques and can induce collagen-degrading matrix metalloproteinases. The latter could be a relevant mechanism in atherosclerotic abdominal aneurysm formation, where MIF expression is correlated with aneurysmal expansion. In summary, MIF has been identified as an important regulator of atherosclerotic vascular disease with exceptional chemokine-like functions. 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.
authors.affiliation: Cardiology Unit, Medical Policlinic-City Center Campus, University of Munich, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schober
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bernhagen
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
mesh_terms: D000783:Aneurysm / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology; D018925:Chemokines / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D008954:Models, Biological; D019718:Receptors, CXCR4 / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000378:metabolism
chemical_list: D018925:Chemokines; D008263:Macrophage Migration-Inhibitory Factors; D019718:Receptors, CXCR4; D023063:Receptors, Interleukin-8B