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Defective Angiogenesis in the Inflammatory Granulation Tissue in Histidine Decarboxylase–deficient Mice but not in Mast Cell–deficient Mice

Ajoy Kumar Ghosh¹, Noriyasu Hirasawa¹, Hiroshi Ohtsu², Takehiko Watanabe² and Kazuo Ohuchi¹

¹ Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi 980-8578, Japan
² Department of Cellular Pharmacology, Graduate School of Medicine, Tohoku University, Miyagi 980-8575, Japan

Address correspondence to Kazuo Ohuchi, Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan. Phone: 81-22-217-6860; Fax: 81-22-217-6859; E-mail: ohuchi-k{at}mail.pharm.tohoku.ac.jp

We have analyzed the role of histamine in the angiogenesis of the granulation tissue in histidine decarboxylase–deficient (HDC^-/-) mice, mast cell–deficient mice (WBB6F1-W/W^V), and their corresponding wild-type mice (HDC^+/+ and WBB6F₁^+/+). In HDC^+/+ mice, subcutaneous implantation of a cotton thread in the dorsum induced granulation tissue formation with angiogenesis, while the topical injection of antivascular endothelial growth factor (VEGF) IgG strongly suppressed them. In HDC^-/- mice which showed lower VEGF levels in the granulation tissue, there was notably less angiogenesis and granulation tissue formation than in HDC^+/+ mice. The topical injection of histamine or the H₂ agonist dimaprit rescued the defective angiogenesis and granulation tissue formation in HDC^-/- mice. There was no significant difference in the granulation tissue formation and angiogenesis between WBB6F1-W/W^V and WBB6F1^+/+ mice. In addition, macrophages in the granulation tissue were found to express HDC. Our findings indicate that histamine derived from nonmast cells plays a significant role in the angiogenesis of the inflammatory granulation tissue.

Key Words: cotton thread • dimaprit • histamine • macrophage • vascular endothelial growth factor

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