The role of PAR1 in protective action of activated protein c under non-immune mast cell activation

Makarova A.M.1, Gorbatcheva L.R.1, Zamolodchikova T.S.2, Rumsh L.D.2, Smirnov M.3, Strukova S.M.1

1. Department of Human and Animal Physiology, Faculty of Biology, Lomonosov Moscow State University
2. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
3. Instrumentation Lab
Section: Experimental/Clinical Study
PubMed Id: 18035722
Year: 2007  Volume: 53  Issue: 4  Pages: 412-426
Activated protein C (APC) regulates the functional activity of mast cells by reducing release of β-hexosaminidase, the marker of mast cell degranulation. APC could modulate the cell secretion of both: the rest mast cells and the activated cells with degranulators, such as proteinase-activated receptor agonist peptide (PAR1-AP) and compound 48/80. PAR1 desensitization with thrombin abolishes the effect of low APC concentration (≤1,5 nМ) on β-hexosaminidase release by mast cells. APC, inactivated with phenilmethylsulfonilftoride (PMSF), did non mimic the enzyme action on mast cells. The duodenal proteinase, duodenase, activates the peritoneal mast cell via PAR1. APC abolishes the proinflammatory action of duodenase and PAR1-AP by means of reducing release of mast cell mediators. Pretreatment of mast cell with L-NAME abolished these APC effects. Thus, APC-induced decrease of mediator release could be attributed to NO generation by mast cells. Our data indicate that PAR1 takes part in the mechanism of regulatory anti-inflammatory APC action.
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Keywords: activated protein C, duodenase, proteinase activated receptors, mast cells, β-hexosaminidase secretion, nitric oxide, inflammation

Makarova, A. M., Gorbatcheva, L. R., Zamolodchikova, T. S., Rumsh, L. D., Smirnov, M., Strukova, S. M. (2007). The role of PAR1 in protective action of activated protein c under non-immune mast cell activation. Biomeditsinskaya Khimiya, 53(4), 412-426.
This paper is also available as the English translation: 10.1007/s11828-008-1006-z
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