GM-CSF is a pleiotropic cytokine that was shown to be mitogenic for keratinocytes (144) and to stimulate migration and proliferation of endothelial cells (44). Together with its potent effect on hematopoietic cells, it has been suggested to play an important role in cutaneous wound repair. Indeed, a series of animal experiments and clinical studies have demonstrated a beneficial effect of GM-CSF for the treatment of normal wounds and chronic ulcers (112). Recently, Mann et al. (170) demonstrated a strong increase in the levels of GM-CSF in skin extracts after generation of full-thickness excisional wounds in mice, although the cellular source has not been determined (170).
A. Overexpression of GM-CSF in the Epidermis of Transgenic Mice Accelerates Wound Reepithelialization
To gain further insight into the possible role of GMCSF in skin wound healing, the same group generated transgenic mice that overexpress this cytokine in the epidermis (34) and generated full-thickness excisional wounds in these animals (170). Interestingly, these animals displayed accelerated wound reepithelialization as a result of increased keratinocyte proliferation. Furthermore, neovascularization and granulation tissue formation were strongly enhanced. Interestingly, several cytokines that are known to be important for wound healing such as TGF-1 were elevated in the wounds of these animals, indicating that GM-CSF stimulates wound repair directly but also indirectly via induction of secondary cytokines (170).