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.
Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Yukikazu
Y
Numata
Tadashi
T
Terui
Ryuhei
R
Okuyama
Noriyasu
N
Hirasawa
Yoshie
Y
Sugiura
Ichiro
I
Miyoshi
Takehiko
T
Watanabe
Atsuo
A
Kuramasu
Hachiro
H
Tagami
Hiroshi
H
Ohtsu
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology* / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000235:genetics; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000235:genetics / Q000502:physiology
D020533:Angiogenesis Inhibitors; D011758:Pyrroles; C105686:SU 5402; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D006632:Histamine; D051496:Receptor, Fibroblast Growth Factor, Type 1; D006640:Histidine Decarboxylase