Macrophage Wnt7b initiates a death program in scheduled vascular regression.

With its passive ability to recognize and engulf dead cells, the macrophage has a critical role to play in modulation of inflammatory and immune responses. In some settings, however, macrophages actively induce apoptosis. We show that macrophage production of Wnt7b is critical for initiation of a death program in capillary endothelial cells during scheduled vascular regression. Wnt7b is required because it activates the canonical Wnt pathway and stimulates cell cycle entry where cells are susceptible to survival signal withdrawal. Survival signal suppression is, in turn, mediated by the Tie2 receptor antagonist angiopoietin-2. This analysis provides a model for integration of the canonical Wnt and Tie2 signaling pathways in vascular endothelium and a mechanistic explanation for macrophage-induced cell death. These findings have important implications for the treatment of vascular diseases including cancer, but also suggest that through the production of mitogens, macrophages may have a general activity in cell health surveillance.

新しくできた毛細血管網が、リモデリングして成熟した血管へと発達していく過程が、個体発生やいろいろな病気の進展に重要な役割を果たしていることが知られているが、そのメカニズムは明らかではない。 Prof. Langは、血管のリモデリングにマクロファージが関わっている可能性を示してきた。今回のセミナーでは、眼内血管をモデル系にした実験より明らかになった、血管リモデリングのメカニズムについてお話したい。