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 WBB6F(1)(+/+)). In HDC(+/+) mice, subcutaneous implantation of a cotton thread in the dorsum induced granulation tissue formation with angiogenesis, while the topical injection of anti-vascular 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 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 non-mast cells plays a significant role in the angiogenesis of the inflammatory granulation tissue.
Ghosh
Ajoy Kumar
AK
Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi 980-8578, Japan.
Hirasawa
Noriyasu
N
Ohtsu
Hiroshi
H
Watanabe
Takehiko
T
Ohuchi
Kazuo
K
D000818:Animals; D017259:Dimaprit / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D003368:Gossypium; D006097:Granulation Tissue / Q000276:immunology; D006632:Histamine / Q000276:immunology* / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000235:genetics / Q000276:immunology*; D008222:Lymphokines / Q000096:biosynthesis; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D017442:Histamine Agonists; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D006632:Histamine; D006640:Histidine Decarboxylase; D017259:Dimaprit