Chymase mediates mast cell-induced angiogenesis in hamster sponge granulomas.
We investigated the contribution of mast cell chymase in mast cell-dependent angiogenesis using the hamster sponge-implant model, where angiogenesis in the granulation tissue surrounding the subcutaneously implanted sponge was evaluated by measuring the hemoglobin content. Daily local injection of compound 48/80 (3-100 microg/site/day), a potent mast cell activator, induced formation of granulomas and angiogenesis in time- and dose-dependent manners. This angiogenic response was inhibited by chymase inhibitors including chymostatin (> or = 1 nmol/site/day), soybean trypsin inhibitor (SBTI; > or = 1.4 nmol/site/day) and lima bean trypsin inhibitor (LBTI; > or = 3.3 nmol/site/day), but not by a tryptase inhibitor like leupeptin (> or = 700 nmol/site/day). Although pyrilamine (> or = 2,580 nmol/site/day), a histamine H1 receptor antagonist, and protamine (300 microg/site/day) also inhibited angiogenesis, these effects were much less pronounced than those by chymase inhibitors. Furthermore, antigen-induced angiogenesis in hamsters pre-sensitized with ovalbumin was also inhibited by the chymase inhibitors by 60-70%. Our results suggest that chymase is a major mediator in mast cell-mediated angiogenesis.
Muramatsu
M
M
Department of Pharmacology, Kitasato University School of Medicine, 1-15-1 Kitasato Sagamihara-shi, Kanagawa 228-8555, Japan.
Katada
J
J
Hattori
M
M
Hayashi
I
I
Majima
M
M
D000818:Animals; D053818:Chymases; D006224:Cricetinae; D006099:Granuloma / Q000473:pathology*; D006454:Hemoglobins / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D006632:Histamine / Q000502:physiology; D006967:Hypersensitivity / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000201:enzymology*; D008647:Mesocricetus; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000473:pathology*; D009842:Oligopeptides / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D006454:Hemoglobins; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; D006493:Heparin; D010047:Ovalbumin; C002101:chymostatin; D012697:Serine Endopeptidases; D053818:Chymases