Activated Mast Cells Increase the Level of Endothelin-1 mRNA in Cocultured Endothelial Cells and Degrade the Secreted Peptide
| Autor: | Marc Baumann, Yenfeng Wang, Outi Saijonmaa, Kari K. Eklund, Petri T. Kovanen, Pirjo Vehmaan-Kreula, Frej Fyhrquist, Metsärinne K, Tuulikki Nyman |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Carboxypeptidases A Carboxypeptidases Biology Exocytosis chemistry.chemical_compound Chymases Endopeptidases medicine Animals Humans Mast Cells RNA Messenger Enzyme Inhibitors Rats Wistar Interleukin 5 Endothelin-1 Serine Endopeptidases Mast cell granule Degranulation Chymase Mast cell Coculture Techniques Rats Cell biology Endothelial stem cell Interleukin 33 medicine.anatomical_structure Biochemistry chemistry Endothelium Vascular Cardiology and Cardiovascular Medicine Histamine |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 22:268-273 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Subendothelial mast cells have been implicated in the pathogenesis of allergic inflammation, in atherosclerosis, and in the regulation of vascular tone. Because endothelin-1 (ET-1) is an important regulator of vascular tone and has also been implicated in the pathogenesis of atherosclerosis, we studied the role of mast cells in the metabolism of endothelial cell-derived ET-1. In mast cell-endothelial cell cocultures, activation of the mast cells with ensuing degranulation was accompanied by the increased expression of ET-1 mRNA in the endothelial cells, yet the immunoreactive ET-1 protein in the coculture medium disappeared almost completely during the 24-hour coculture. Activation of the mast cells with the ensuing degranulation resulted in proteolytic degradation of ET-1 by the 2 neutral proteases, chymase and carboxypeptidase A, of the exocytosed mast cell granules. With synthetic ET-1 and purified mast cell granule enzymes, efficient degradation of ET-1 by chymase and carboxypeptidase A was verified. These in vitro results imply a novel role for mast cell-derived neutral proteases in ET-1 metabolism and suggest that activated subendothelial mast cells are important local regulators of ET-1 metabolism. |
| Databáze: | OpenAIRE |
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