TY  - JOUR
A1  - Ukan, Ürün
A1  - Delgado Lagos, Fredy Andrés
A1  - Kempf, Sebastian
A1  - Günther, Stefan
A1  - Siragusa, Mauro
A1  - Fißlthaler, Beate
A1  - Fleming, Ingrid
T1  - Effect of thrombin on the metabolism and function of murine macrophages
T2  - Cells
N2  - 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.
KW  - SMOC1
KW  - macrophage polarization
KW  - thrombin
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/81845
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-818451
SN  - 2073-4409
N1  - This work was supported by the Deutsche Forschungsgemeinschaft (GRK 2336 TP05 Project ID 321115009, SFB 834/3 A5 Project ID: 75732319, Cardio-Pulmonary Institute, EXC 2026, Project ID: 390649896).
N1  - Gefördert durch den Open-Access-Publikationsfonds der Goethe-Universität
VL  - 11
IS  - 10, art. 1718
SP  - 1
EP  - 17
PB  - MDPI
CY  - Basel
ER  -