1. Lomonosov Moscow State University, School of Biology, Department of Human & Animal Physiology 2. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences 3. Russian Cardiology Research and Production Complex, Russian Ministry of Health
Abstract: Some serine proteinases of haemostasis can regulate blood clotting and inflammation acting at proteinase-activated receptors (PARs). It is known that the anticoagulant proteinase, activated protein C (APC), exhibits anti-inflammatory effects on endothelial cells and macrophages and this involves endothelial protein C receptor - EPCR and proteinase-activated receptor - PAR1. We have studied the effect of wide range of APC concentrations on functional activity of rat peritoneal mast cells (PMC), which secrete the proinflammatory mediators, under normal conditions and during acute inflammation in rats. APC was able to reduce β-hexosaminidase release from PMC. APC at very low concentrations (0.2-2 nM) modulated the mediator secretion from PMC under normal conditions and also during acute inflammation in rats. APC abolished the proinflammatory activity of duodenase (80 nM), the proteinase from gastrointestinal tract and mast cells. Mast cells pretreated with cathepsin G (PAR1 antagonist) or duodenase abolished protective antiinflammatory effect of low concentrations of APC on PMC degranulation. Our data indicated that blockade of the mast cells proinflammatory mediator secretion by APC involved PAR1 activation.
Reference: Makarova A.M., Gorbacheva L.R., Zamolodchikova T.S., Rumsh L.D., Bespalova Zh.D., Strukova S.M., Various effects of serine proteinases, activated protein c and duodenase, on mast cells, Biomeditsinskaya khimiya, 2008, vol: