Platelets are a previously unrecognised source of MIF

Autor: R. Bucala, Jürgen Bernhagen, Sabine Tillmann, Theresa H. Wirtz, P. von Hundelshausen, T. Strüßmann
Rok vydání: 2013
Předmět:
0301 basic medicine
Blood Platelets
medicine.medical_specialty
Chemokine
Monocyte chemotaxis
animal diseases
medicine.medical_treatment
chemical and pharmacologic phenomena
Cell Separation
Monocytes
Cell Line
03 medical and health sciences
Mice
0302 clinical medicine
Cell Movement
Internal medicine
otorhinolaryngologic diseases
medicine
Macrophage
Animals
Humans
Platelet
Platelet activation
Antibodies
Blocking
Macrophage Migration-Inhibitory Factors
biology
Thrombin
Chemotaxis
Hematology
respiratory system
Atherosclerosis
Flow Cytometry
Molecular biology
biological factors
Chemokine CXCL12
Adenosine Diphosphate
Intramolecular Oxidoreductases
Lipoproteins
LDL
Mice
Inbred C57BL
Protein Transport
030104 developmental biology
Endocrinology
Cytokine
030220 oncology & carcinogenesis
biology.protein
Macrophage migration inhibitory factor
Collagen
Inflammation Mediators
Zdroj: Thrombosis and haemostasis. 110(5)
ISSN: 2567-689X
Popis: SummaryMacrophage migration inhibitory factor (MIF) is an inflammatory cytokine with chemokine-like functions and a role in atherogenesis. MIF is secreted by various cells including endothelial cells and macrophages. Platelets are another prominent cell type with a role in atherogenesis and are a rich source of atherogenic chemokines. We asked whether platelets express and secrete MIF. In comparison, CXCL12 release was determined. We examined the subcellular localisation of MIF in platelets/ megakaryocytes, studied its co-localisation with other plateletderived mediators and asked whether platelets contain MIF mRNA. Moreover, we probed the functional role of platelet-derived MIF in inflammatory cell recruitment. Using Western blot and ELISA, we demonstrated and quantitated MIF protein in human and mouse platelets. Applying confocal-microscopy, MIF was found to localise in granularlike structures, but did not co-localise with known platelet cytokines. qPCR indicated that platelets contain low levels of MIF mRNA. ELISA measurements from human platelet supernatants showed that, whereas thrombin and collagen triggered the release of MIF and CXCL12, ADP and oxidised LDL promoted CXCL12 but not MIF secretion. Using Transwell assays, we demonstrated that platelet supernatants promoted monocyte chemotaxis and that this was blocked by neutralising MIF antibodies. This is the first report demonstrating MIF secretion from activated platelets, suggesting that platelets are a previously unrecognised source of MIF in inflammatory processes. There are distinct activating stimuli for MIF and CXCL12 secretion. A substantial portion of the chemotactic capacity of stimulated platelet supernatants is contributed by MIF, suggesting a role for platelet-derived MIF in atherogenic cell recruitment.
Databáze: OpenAIRE
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