Myxoma viral serpin, Serp-1, a unique interceptor of coagulation and innate immune pathways

Thrombosis and Haemostasis
Kasinath ViswanathanAlexandra Lucas

Abstract

Serpins maintain haemostasis through regulation of serine proteinases in the thrombotic and thrombolytic pathways. Viruses encode serpins that can alter thrombotic and thrombolytic responses producing, in some cases, disseminated intravascular coagulation (DIC). However, it has not been precisely defined how viral serpins induce these profound responses. The rabbit myxoma viral serpin, Serp-1 inhibits urokinase- and tissue-type plasminogen activators (uPA and tPA), plasmin and factor Xa in vitro and exhibits remarkable anti-inflammatory activity in various animal models. The effects of Serp-1 on activation of human platelets, endothelial cells, monocytes and T cells that mediate thrombosis and innate immune responses were therefore examined. We found that Serp-1 attenuated platelet and mononuclear cell adhesion to fibronectin and collagen. Serp-1 similarly inhibited monocyte migration into the peritoneum. Serp-1 inhibition of monocyte migration was lost in uPA receptor (uPAR) deficient mice. Serp-1 bound to the plasma membrane surface and altered uPA activation of endothelial cells (p=0.001), thrombin activation of platelets (p=0.021) and phorbol ester activation of endothelial (p=0.047), monocyte (p=0.011) and Jurkat T cells (...Continue Reading

Citations

Dec 5, 2008·Journal of Leukocyte Biology·Kasinath ViswanathanAlexandra R Lucas
Dec 2, 2015·The Journal of Biological Chemistry·Sriram AmbadapadiAlexandra Lucas
Sep 11, 2020·International Journal of Molecular Sciences·Augusto Martins LimaNikolaos Stergiopulos
Jul 6, 2016·Human Molecular Genetics·Kim A StaatsLudo Van Den Bosch
Feb 13, 2020·Scientific Reports·Jordan R YaronAlexandra R Lucas
Apr 5, 2020·Journal of Clinical Medicine·Jordan R YaronAlexandra R Lucas

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