Live imaging of wound angiogenesis reveals macrophage orchestrated vessel sprouting and regression

Gurevich, David B; Severn, Charlotte E; Twomey, Catherine; Greenhough, Alexander; Cash, Jenna; Toye, Ashley M; Mellor, Harry; Martin, Paul

Abstract

© 2018 The Authors. Published under the terms of the CC BY 4.0 license Wound angiogenesis is an integral part of tissue repair and is impaired in many pathologies of healing. Here, we investigate the cellular interactions between innate immune cells and endothelial cells at wounds that drive neoangiogenic sprouting in real time and invivo. Our studies in mouse and zebrafish wounds indicate that macrophages are drawn to wound blood vessels soon after injury and are intimately associated throughout the repair process and that macrophage ablation results in impaired neoangiogenesis.Macrophages also positively influence wound angiogenesis by driving resolution of anti-angiogenic wound neutrophils. Experimental manipulation of the wound environment to specifically alter macrophage activation state dramatically influences subsequent blood vessel sprouting, with premature dampening of tumour necrosis factor-α expression leading to impaired neoangiogenesis. Complementary human tissue culture studies indicate that inflammatory macrophages associate with endothelial cells and are sufficient to drive vessel sprouting via vascular endothelial growth factor signalling. Subsequently, macrophages also play a role in blood vessel regression during the resolution phase of wound repair, and their absence, or shifted activation state, impairs appropriate vessel clearance.

• Journal Article Type: Article
• Acceptance Date: Apr 30, 2018
• Online Publication Date: Jun 4, 2018
• Publication Date: Jul 2, 2018
• Deposit Date: Feb 13, 2019
• Publicly Available Date: Feb 14, 2019
• Journal: EMBO Journal
• Print ISSN: 0261-4189
• Electronic ISSN: 1460-2075
• Publisher: EMBO Press
• Peer Reviewed: Peer Reviewed
• Volume: 37
• Issue: 13
• Article Number: e97786
• DOI: https://doi.org/10.15252/embj.201797786
• Keywords: angiogenesis, inflammation, macrophages, neutrophils, wound
• Public URL: https://uwe-repository.worktribe.com/output/864995
• Publisher URL: https://doi.org/10.15252/embj.201797786
• Contract Date: Feb 13, 2019