The Accelerating Effect of Histamine on the Cutaneous Wound-Healing Process Through the Action of Basic Fibroblast Growth Factor

• Published in: Journal of investigative dermatology Vol. 126; no. 6; pp. 1403 - 1409
• Main Authors: Numata, Yukikazu, Terui, Tadashi, Okuyama, Ryuhei, Hirasawa, Noriyasu, Sugiura, Yoshie, Miyoshi, Ichiro, Watanabe, Takehiko, Kuramasu, Atsuo, Tagami, Hachiro, Ohtsu, Hiroshi
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01.06.2006; Nature Publishing; Elsevier Limited
• Subjects: Angiogenesis Inhibitors - pharmacology; Animals; Biological and medical sciences; Dermatology; Fibroblast Growth Factor 2 - analysis; Fibroblast Growth Factor 2 - metabolism; Histamine - pharmacology; Histamine - physiology; Histidine Decarboxylase - genetics; Macrophages - drug effects; Medical sciences; Mice; Mice, Knockout; Mice, Transgenic; Neovascularization, Physiologic - drug effects; Pyrroles - pharmacology; Receptor, Fibroblast Growth Factor, Type 1 - antagonists & inhibitors; Skin - cytology; Skin - drug effects; Skin - metabolism; Vascular Endothelial Growth Factor A - analysis; Vascular Endothelial Growth Factor A - metabolism; Wound Healing - drug effects; Wound Healing - genetics; Wound Healing - physiology; Histamine; Angiogenic factor; Dermatology; Basic fibroblast growth factor; Skin; Process; Cicatrization
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/sj.jid.5700253

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.