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Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
Effect of Thrombin on the Metabolism and Function of Murine Macrophages
Ürün Ukan1, Fredy Delgado Lagos1, Sebastian Kempf1
1Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, 60596 Frankfurt am Main, Germany.
Abstract:
Macrophages are plastic and heterogeneous immune cells that adapt pro- or anti-inflammatory phenotypes upon exposure to different stimuli. Even though there has been evidence supporting a crosstalk between coagulation and innate immunity, the way in which protein components of the hemostasis pathway influence macrophages remains unclear. We investigated the effect of thrombin on macrophage polarization. On the basis of gene expression and cytokine secretion, our results suggest that polarization with thrombin induces an anti-inflammatory, M2-like phenotype. In functional studies, thrombin polarization promoted oxLDL phagocytosis by macrophages, and conditioned medium from the same cells increased endothelial cell proliferation. There were, however, clear differences between the classical M2a polarization and the effects of thrombin on gene expression. Finally, the deletion and inactivation of secreted modular Ca2+-binding protein 1 (SMOC1) attenuated phagocytosis by thrombin-stimulated macrophages, a phenomenon revered by the addition of recombinant SMOC1. Manipulation of SMOC1 levels also had a pronounced impact on the expression of TGF-β-signaling-related genes. Taken together, our results show that thrombin induces an anti-inflammatory macrophage phenotype with similarities as well as differences to the classical alternatively activated M2 polarization states, highlighting the importance of tissue levels of SMOC1 in modifying thrombin-induced macrophage polarization.
Insights
Thrombin, a key coagulation factor, induces an anti-inflammatory macrophage response, promoting phagocytosis and endothelial cell proliferation. Secreted modular Ca2+-binding protein 1 (SMOC1) plays a crucial role in mediating these thrombin-induced macrophage effects.
Area of Science:
- Immunology
- Coagulation Biology
- Cellular Biology
Background:
- Macrophages are immune cells with adaptable phenotypes, crucial in inflammation.
- The interaction between the coagulation system and innate immunity is increasingly recognized.
- The specific influence of hemostasis proteins on macrophage polarization is not fully understood.
Purpose of the Study:
- To investigate the effect of thrombin on macrophage polarization.
- To elucidate the role of secreted modular Ca2+-binding protein 1 (SMOC1) in thrombin-mediated macrophage responses.
Main Methods:
- Gene expression analysis and cytokine secretion profiling.
- Functional assays including oxLDL phagocytosis and endothelial cell proliferation.
- Genetic manipulation of SMOC1 levels (deletion, inactivation, and recombinant addition).
Main Results:
- Thrombin stimulation induced an anti-inflammatory, M2-like macrophage phenotype.
- Thrombin-polarized macrophages exhibited enhanced oxLDL phagocytosis and promoted endothelial cell proliferation.
- SMOC1 deletion/inactivation attenuated thrombin-induced phagocytosis, while recombinant SMOC1 rescued this effect.
- SMOC1 manipulation significantly impacted TGF-β signaling gene expression.
Conclusions:
- Thrombin induces a unique anti-inflammatory macrophage phenotype distinct from classical M2 polarization.
- SMOC1 is a critical mediator of thrombin-induced macrophage polarization and function.
- These findings highlight the intricate crosstalk between coagulation and macrophage immunity, with SMOC1 as a key regulator.
