In EDS ansehen

Myeloid SOCS3 Deficiency Regulates Angiogenesis via Enhanced Apoptotic Endothelial Cell Engulfment

Gespeichert in:
Bibliographische Detailangaben
Titel: Myeloid SOCS3 Deficiency Regulates Angiogenesis via Enhanced Apoptotic Endothelial Cell Engulfment
Autoren: Korovina, Irina, Neuwirth, Ales, Sprott, David, Troullinaki, Maria, Poitz, David M., Deussen, Andreas, Klotzsche-von Ameln, Anne
Quelle: Journal of Innate Immunity. 12:248-256
Verlagsinformationen: S. Karger AG, 2019.
Publikationsjahr: 2019
Schlagwörter: 0301 basic medicine, Mice, 0303 health sciences, 03 medical and health sciences, Phagocytosis, Suppressor of Cytokine Signaling 3 Protein, Apoptosis/immunology [MeSH], Neovascularization, Physiologic/genetics [MeSH], Suppressor of Cytokine Signaling 3 Protein/immunology [MeSH], Suppressor of Cytokine Signaling 3 Protein/deficiency [MeSH], Myeloid Cells/immunology [MeSH], Animals [MeSH], Mice, Transgenic [MeSH], Mice [MeSH], Suppressor of cytokine signaling 3, Phagocytosis [MeSH], Growth arrest-specific 6, Mer, Apoptosis/genetics [MeSH], Endothelial Cells/immunology [MeSH], Angiogenesis, Research Article, Neovascularization, Physiologic/immunology [MeSH], Animals, Endothelial Cells, Neovascularization, Physiologic, Apoptosis, Mice, Transgenic, Myeloid Cells
Beschreibung: Mononuclear phagocytes, such as macrophages and microglia, are key regulators of organ homeostasis including vascularization processes. Here, we investigated the role of the suppressor of cytokine signaling 3 (SOCS3) in myeloid cells as a regulator of mononuclear phagocyte function and their interaction with endothelial cells in the context of sprouting angiogenesis. As compared to SOCS3-sufficient counterparts, SOCS3-deficient microglia and macrophages displayed an increased phagocytic activity toward primary apoptotic endothelial cells, which was associated with an enhanced expression of the opsonin growth arrest-specific 6 (Gas6), a major prophagocytic molecule. Furthermore, we found that myeloid SOCS3 deficiency significantly reduced angiogenesis in an ex vivo mouse aortic ring assay, which could be reversed by the inhibition of the Gas6 receptor Mer. Together, SOCS3 in myeloid cells regulates the Gas6/Mer-dependent phagocytosis of endothelial cells, and thereby angiogenesis-related processes. Our findings provide novel insights into the complex crosstalk between mononuclear phagocytes and endothelial cells, and may therefore provide a new platform for the development of new antiangiogenic therapies.
Publikationsart: Article
Conference object
Sprache: English
ISSN: 1662-8128
1662-811X
DOI: 10.1159/000502645
Zugangs-URL: https://www.karger.com/Article/Pdf/502645
https://pubmed.ncbi.nlm.nih.gov/31574508
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265721
https://europepmc.org/article/MED/31574508
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265721
https://pubmed.ncbi.nlm.nih.gov/31574508/
https://repository.publisso.de/resource/frl:6478875
Rights: CC BY NC ND
Dokumentencode: edsair.doi.dedup.....51b7f88c24aa14a89262a01360555fcc
Datenbank: OpenAIRE
Beschreibung
Abstract:Mononuclear phagocytes, such as macrophages and microglia, are key regulators of organ homeostasis including vascularization processes. Here, we investigated the role of the suppressor of cytokine signaling 3 (SOCS3) in myeloid cells as a regulator of mononuclear phagocyte function and their interaction with endothelial cells in the context of sprouting angiogenesis. As compared to SOCS3-sufficient counterparts, SOCS3-deficient microglia and macrophages displayed an increased phagocytic activity toward primary apoptotic endothelial cells, which was associated with an enhanced expression of the opsonin growth arrest-specific 6 (Gas6), a major prophagocytic molecule. Furthermore, we found that myeloid SOCS3 deficiency significantly reduced angiogenesis in an ex vivo mouse aortic ring assay, which could be reversed by the inhibition of the Gas6 receptor Mer. Together, SOCS3 in myeloid cells regulates the Gas6/Mer-dependent phagocytosis of endothelial cells, and thereby angiogenesis-related processes. Our findings provide novel insights into the complex crosstalk between mononuclear phagocytes and endothelial cells, and may therefore provide a new platform for the development of new antiangiogenic therapies.
ISSN:16628128
1662811X
DOI:10.1159/000502645