Myeloid SOCS3 Deficiency Regulates Angiogenesis via Enhanced Apoptotic Endothelial Cell Engulfment.
J Innate Immun
; 12(3): 248-256, 2020.
Article
en En
| MEDLINE
| ID: mdl-31574508
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Apoptosis
/
Neovascularización Fisiológica
/
Células Mieloides
/
Células Endoteliales
/
Proteína 3 Supresora de la Señalización de Citocinas
Límite:
Animals
Idioma:
En
Revista:
J Innate Immun
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania