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.