The accelerating effect of histamine on the cutaneous wound-healing process through the action of basic fibroblast growth factor

This study revealed that the absence of histamine in histidine decarboxylase gene-knockout (HDC^-/-) mice resulted in delayed cutaneous wound healing and that exogenously administered histamine compensated this process. With the overproduction of histamine in HDC gene-transgenic mice, the healing was accelerated compared to the HDC^+/+ mice. These results indicate that histamine positively accelerated the cutaneous wound healing. Macrophage recruitment and angiogenesis at the wound edge were specifically impaired in HDC^-/- mice, and histamine-treated wounds in HDC^-/- mice demonstrated increased macrophage recruitment and angiogenesis. The amount of basic fibroblast growth factor (bFGF) in protein level at the wound edge was higher in HDC^+/+ mice, especially on the 3rd and 5th day of wound healing compared to those in HDC^-/- mice. Topically administered SU5402, a specific antagonist to fibroblast growth factor receptor-1 tyrosine kinase, to the wound surface suppressed the wound healing in HDC^+/+ mice but not in HDC^-/- mice. Moreover, SU5402 reduced macrophage recruitment and angiogenesis in HDC^+/+ mice. From these observations, it was concluded that the accelerated wound-healing activity of histamine was mediated by the activity of bFGF, which leads to angiogenesis, and macrophage recruitment in the wound-healing process.