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  Effect of Thrombin on the Metabolism and Function of Murine Macrophages

Ukan, U., Lagos, F. D., Kempf, S., Gunther, S., Siragusa, M., Fisslthaler, B., et al. (2022). Effect of Thrombin on the Metabolism and Function of Murine Macrophages. CELLS, 11(10): 1718. doi:10.3390/cells11101718.

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 Creators:
Ukan, Ueruen, Author
Lagos, Fredy Delgado, Author
Kempf, Sebastian, Author
Gunther, Stefan1, Author              
Siragusa, Mauro, Author
Fisslthaler, Beate, Author
Fleming, Ingrid, Author
Affiliations:
1Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591695              

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 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-beta-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.

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 Dates: 2022-05-23
 Publication Status: Published online
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 Rev. Type: -
 Identifiers: ISI: 000801271000001
DOI: 10.3390/cells11101718
PMID: 35626753
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Title: CELLS
Source Genre: Journal
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Pages: - Volume / Issue: 11 (10) Sequence Number: 1718 Start / End Page: - Identifier: -