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 VTBB6F(1)(+/+)). 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 H-2 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 VTBB6F1-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.