Chymase is a proteolytic enzyme present in mast cell granules that is released by mast cell degranulation with tryptase, histamines, and other mediators. To elucidate the roles of mast cells in various biological processes, including fibrosis and wound repair, it is necessary to know the effects of chymase on fibroblasts and vascular endothelial cells. We examined the effect of human chymase on human dermal microvascular endothelial cells (HDMEC) and human dermal fibroblasts (HDF). Chymase did not affect HDMEC growth, but it did stimulate the proliferation of HDF at 1nM concentration. This growth-promoting activity was completely inhibited by the addition of the chymase substrate peptide, Suc-Val-Pro-Phe
P (OPh)
2. Chymase did not have any effect on ICAM-1 or VCAM-1 expression in HDMEC and HDF. The present study suggests that the mitogenic effect of chymase released from mast cells on dermal fibroblasts may be involved in some pathological and physiological processes. Another chymase inhibitory agent, which is a quinazoline derivative, stimulated the growth of HDMEC and enhanced VCAM-1expression in the cells, suggesting an angiogenic effect.
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