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 mu g/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 (greater than or equal to 1 nmol/site/day), soybean trypsin inhibitor (SBTI; greater than or equal to 1.4 nmol/site/day) and lima bean trypsin inhibitor (LBTI; greater than or equal to 3.3 nmol/site/day), but not by a tryptase inhibitor like leupeptin (greater than or equal to 700 nmol/site/day). Although pyrilamine (greater than or equal to 2,580 nmol/site/day), a histamine H1 receptor antagonist, and protamine (300 mu g/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. (C) 2000 Elsevier Science B.V. All rights reserved.