Effect of mast cell–derived mediators and mast cell–related neutral proteases on human dermal fibroblast proliferation and type I collagen production

• Published in: Journal of allergy and clinical immunology 2000-07, Vol.106 (1), p.S78-S84
• Main Authors: Abe, Masatoshi, Kurosawa, Motohiro, Ishikawa, Osamu, Miyachi, Yoshiki
• Format: Article
• Language: English
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Biological and medical sciences; Cell Division - drug effects; Cells, Cultured; Collagen - biosynthesis; Cysteine Endopeptidases - pharmacology; dermal fibroblast; Fibroblasts - cytology; Fibroblasts - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Inflammation Mediators - pharmacology; Mast cell; Mast Cells - chemistry; Mast Cells - enzymology; mediator; neutral protease; Organs and cells involved in the immune response; proliferation; type I collagen
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1067/mai.2000.106058

Background: Possible involvement of mast cells in various fibrotic conditions has been suggested, but the relative contribution of each mast cell mediator and neutral protease to fibroproliferative activity remains to be elucidated. Objective: We investigated the effect of mast cell-derived mediators and mast cell-related neutral proteases on type I collagen production and proliferation by human dermal fibroblasts. Methods: Mast cell–derived mediators or neutral proteases were added to cultured fibroblasts from normal dermis, and cell proliferation and type I collagen synthesis were assayed. Results: Fibroblast proliferation was increased by 2.8 × 10-9 mol/L prostaglandin D2 and 10 μg/mL carboxypeptidase A, but not by leukotriene D4 or cathepsin G at the concentrations studied. Proliferation was increased by tryptase in a concentration-dependent manner, and a significant increase was observed at concentrations of 1 and 10 μg/mL. Production of type I collagen by fibroblasts was increased in the presence of 2.0 × 10–9 mol/L leukotriene D4 and 10 μg/mL tryptase. Conclusion: Mast cell–derived mediators prostaglandin D2 and leukotriene D4 and mast cell–related neutral proteases carboxypeptidase A and tryptase increase the proliferation and type I collagen production of human dermal fibroblasts in various manners. (J Allergy Clin Immunol 2000;106:S78-84.)