Impaired cutaneous wound healing in granulocyte/macrophage colony-stimulating factor knockout mice.
BACKGROUND
Wound healing involves various cells and cytokines, resulting in the regular progression of remodelling events. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a multifunctional pleiotropic cytokine and is known to facilitate wound healing, although the precise molecular and cellular mechanisms remain to be explored.


OBJECTIVE
To use GM-CSF gene knockout (GM-CSF KO) mice to investigate the role of GM-CSF in cutaneous wound healing following full-thickness skin injury.


METHODS
Full-thickness skin wounds were made in GM-CSF KO and wild-type mice. The wound closure, leucocyte infiltration, vascularization and extent of cytokine production were determined.


RESULTS
Wound healing was significantly delayed in GM-CSF KO mice, accompanied by reduced cytokine production (interleukin-6, monocyte chemoattractant protein-1 and macrophage inflammatory protein-2), and platelet-endothelial cell adhesion molecule-1 expression. Consequently there was reduced recruitment of neutrophils and macrophages and reduced vascularization in the wounds of GM-CSF KO mice. Although collagen deposition was delayed, it was significantly increased in the wounds of the GM-CSF KO mice in the later stages of wound healing.


CONCLUSIONS
We conclude that GM-CSF plays an important role in the complex network of effector molecules that regulate keratinocyte proliferation and the inflammatory response. These data have important implications for further development of the therapeutic manipulation of wound healing using GM-CSF.
Fang
Y
Y
Department of Plastic Surgery, The Third People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 201900, China.
Gong
S-J
SJ
Xu
Y-H
YH
Hambly
B D
BD
Bao
S
S
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D015603:Keratinocytes / Q000473:pathology* / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000098:blood supply / Q000293:injuries*; D014945:Wound Healing / Q000502:physiology*
D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor