Deficiency of CX3CR1 delays burn wound healing and is associated with reduced myeloid cell recruitment and decreased sub-dermal angiogenesis

• Published in: Burns Vol. 37; no. 8; pp. 1386 - 1393
• Main Authors: Clover, Anthony J.P, Kumar, Arun H.S, Caplice, Noel M
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.12.2011; Elsevier
• Subjects: Animals; Biological and medical sciences; Burn healing; Burns; Burns - metabolism; Burns - pathology; Burns - physiopathology; Chemokine CX3CL1 - metabolism; Critical Care; CX3C Chemokine Receptor 1; CX3CR1; Endothelial Cells - pathology; Immunohistochemistry; Macrophages; Macrophages - pathology; Medical sciences; Mice; Mice, Transgenic; Models, Animal; Monocytes; Myeloid Cells - pathology; Neovascularization, Physiologic - physiology; Receptors, Chemokine - deficiency; Skin - blood supply; Skin - cytology; Traumas. Diseases due to physical agents; Wound healing; Wound Healing - physiology; CX3CR1; Monocytes; Wound healing; Macrophages; Burn healing; Skin disease; Monocyte; Deficiency; Myeloid cell; Wound; Recruitment; Burn; Angiogenesis; Healing agent; Derm; Cicatrization; CX3CR1 chemokine receptor; Macrophage
• ISSN: 0305-4179; 1879-1409
• DOI: 10.1016/j.burns.2011.08.001

Abstract The development of a good blood supply is a key step in burn wound healing and appears to be regulated in part by myeloid cells. CX3CR1 positive cells have recently been identified as myeloid cells with a potential role in angiogenesis. The role of functional CX3CR1 system in burn wound healing is not previously investigated. A 2% contact burn was induced in CX3CR1+/gfp and CX3CR1gfp/gfp mice. These transgenic mice facilitate the tracking of CX3CR1 cells (CX3CR1+/gfp ) and allow evaluation of the consequence of CX3CR1 functional knockout (CX3CR1gfp/gfp ) on burn wound healing. The progression of wound healing was monitored before tissue was harvested and analyzed at day 6 and day 12 for migration of CX3CR1 cells into burn wound. Deficiency of a functional CX3CR1 system resulted in decreased recruitment of CX3CR1 positive cells into the burn wound associated with decreased myeloid cell recruitment ( p < 0.001) and reduced maintenance of new vessels ( p < 0.001). Burn wound healing was prolonged ( p < 0.05). Our study is the first to establish a role for CX3CR1 in burn wound healing which is associated with sub-dermal angiogenesis. This chemokine receptor pathway may be attractive for therapeutic manipulation as it could increase sub dermal angiogenesis and thereby improve time to healing.