Platelet-derived MIF: a novel platelet chemokine with distinct recruitment properties
Theresa H Wirtz1, Sabine Tillmann1, Tim Strüßmann1
1Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen, Germany.
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.
Insights
Platelet-derived Macrophage Migration Inhibitory Factor (MIF) is secreted later than other chemokines but significantly enhances monocyte adhesion and influences clot retraction, suggesting a key role in atherosclerosis.
Area of Science:
- Biochemistry
- Immunology
- Cardiovascular Research
Background:
- Macrophage Migration Inhibitory Factor (MIF) is an inflammatory cytokine with chemokine-like functions implicated in atherosclerosis.
- Platelets are a newly identified source of MIF, alongside macrophages and endothelial cells.
- The functional significance of platelet-derived MIF and its comparison to other platelet chemokines remain unclear.
Purpose of the Study:
- To define the secretion pattern of platelet-derived MIF.
- To characterize the functional profile of platelet-derived MIF in comparison to known atherogenic platelet chemokines.
- To investigate the role of platelet MIF in monocyte adhesion and clot retraction.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) to determine MIF secretion kinetics.
- Platelet activation assays (aggregation, CD62P exposure, chemokine secretion).
- Monocyte transmigration and adhesion assays using conditioned platelet supernatants and MIF blockade.
- Analysis of clot retraction dynamics.
Main Results:
- MIF is released from thrombin-stimulated platelets after 2 hours, significantly later than CXCL12 and CXCL4.
- Platelet-derived MIF, unlike CXCL12, did not enhance platelet activation but attenuated ADP-induced calcium transients.
- Platelet MIF demonstrated stronger chemotactic activity for monocytes than CXCL12 and substantially contributed to monocyte adhesion on endothelial cells.
- MIF was observed to delay clot retraction.
Conclusions:
- Platelet-derived MIF exhibits delayed secretion kinetics and distinct autocrine/paracrine modulation compared to other platelet chemokines.
- MIF is a significant platelet-derived chemotactic factor for monocytes with clot-modulating properties.
- Platelet MIF may play a crucial role in inflammatory diseases like atherosclerosis.
