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

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

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

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 in vivo 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.

Original languageEnglish
Article numbere97786
JournalEMBO Journal
Volume37
Issue number13
Early online date4 Jun 2018
DOIs
Publication statusPublished - 2 Jul 2018

Keywords

  • Animals
  • Animals, Genetically Modified
  • Cells, Cultured
  • Diagnostic Imaging
  • Fibroblasts
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Macrophages/physiology
  • Male
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic
  • Wound Healing/physiology
  • Zebrafish/genetics

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