The Role of PAR1 in Protective Action of Activated Protein C during Nonimmune Activation of Mast Cells

摘要

Activated protein C (APC) regulates the functional activity of mast cells by reducing release of3-hexosaminidase, the marker of mast cell degranulation. APC modulated not only spontaneous secretion frommast 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-hexosamini-dase secretion induced by low APC concentrations (≤1.5 nM). APC inactivated by phenylmethylsulfonyl fluo-ride (PMSF), did non mimic the enzyme action on mast cells. Duodenase (the duodenal proteinase) activatedperitoneal mast cell via PAR1. APC abolished the proinflammatory effect of duodenase and PAR1-AP by reduc-ing release of mast cell mediators. The effect of APC could be attributed to nitric oxide generation by mast cellsbecause in the presence of L-NAME the secretory function restored. These data suggest involvement of mastcell PAR1 into regulatory mechanism responsible for the anti-inflammatory effect of APC.