Abstract:
OBJECTIVE:Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine with chemokine-like functions that plays a role in several inflammatory diseases including atherosclerosis. We recently demonstrated that in addition to macrophages and endothelial cells, platelets are a source of MIF. However, the functional relevance of platelet-derived MIF and differences to other platelet chemokines are unclear. Here, we sought to define the secretion pattern of platelet MIF and to characterize its functional profile in comparison with known atherogenic platelet chemokines. METHODS AND RESULTS:Applying ELISA, we show that MIF is released from thrombin-stimulated platelets after 2 h, whereas CXCL12 and CXCL4 are secreted within minutes. Applied to platelets, MIF, unlike CXCL12, did not enhance platelet activation as analyzed by platelet aggregation, CD62P exposure and chemokine secretion studies. In contrast, both MIF and CXCL12 attenuated ADP-induced calcium transients in platelets. Transmigration and monocyte flow adhesion assays toward conditioned platelet supernatants together with MIF antibody blockade or supernatants from Mif(-/-) mice suggested that platelet-derived MIF has a stronger chemotactic activity than CXCL12 at its respective optimal secretion interval, and showed that platelet MIF substantially contributes to monocyte adhesion on endothelial layers. Moreover, MIF was found to delay clot retraction. CONCLUSIONS:We demonstrate that MIF differs from other platelet-derived chemokines by delayed secretion kinetics and by a distinct autocrine/paracrine modulation potential. Importantly, MIF was found to be a major platelet-derived chemotactic recruitment factor with clot-modulating properties and therefore might be relevant in inflammatory diseases such as atherosclerosis.
journal_name
Atherosclerosisjournal_title
Atherosclerosisauthors
Wirtz TH,Tillmann S,Strüßmann T,Kraemer S,Heemskerk JW,Grottke O,Gawaz M,von Hundelshausen P,Bernhagen Jdoi
10.1016/j.atherosclerosis.2014.12.039subject
Has Abstractpub_date
2015-03-01 00:00:00pages
1-10issue
1eissn
0021-9150issn
1879-1484pii
S0021-9150(14)01661-Xjournal_volume
239pub_type
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