The role of PAR1 in protective action of activated protein C during nonimmune activation of mast cells |
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| Authors: | A M Makarova L R Gorbacheva T S Zamolodchikova L D Rumsh M D Smirnov S M Strukova |
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| Institution: | (1) Department of Human and Animal Physiology, School of Biology, Lomonosov Moscow State University, Moscow, 119992, Russia;(2) Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia;(3) Instrumentation Lab., Orangeburg, NY, USA |
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| Abstract: | Activated protein C (APC) regulates the functional activity of mast cells by reducing release of β-hexosaminidase, the marker of mast cell degranulation. APC modulated not only spontaneous secretion from mast cells, but also secretion induced by the degranulators, proteinase-activated receptor agonist peptide (PAR1-AP) and compound 48/80. PAR1 desensitization by thrombin abolished the decrease of β-hexosaminidase secretion induced by low APC concentrations (≤1.5 nM). APC inactivated by phenylmethylsulfonyl fluoride (PMSF), did non mimic the enzyme action on mast cells. Duodenase (the duodenal proteinase) activated peritoneal mast cell via PAR1. APC abolished the proinflammatory effect of duodenase and PAR1-AP by reducing release of mast cell mediators. The effect of APC could be attributed to nitric oxide generation by mast cells because in the presence of L-NAME the secretory function restored. These data suggest involvement of mast cell PAR1 into regulatory mechanism responsible for the anti-inflammatory effect of APC. |
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| Keywords: | activated protein C duodenase proteinase activated receptors mast cells β -hexosaminidase secretion nitric oxide inflammation |
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