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

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.