Potential Role of Platelet-Activating C-Type Lectin-Like Proteins in Viper Envenomation Induced Thrombotic Microangiopathy Symptom.

Chengbo Long,Feilong Wu,Chuanbin Shen,Huiwen Tian,Ren Lai,Ming Liu,James Mwangi,Qiumin Lu,Tarek Mohamed Abd El-Aziz,Ya Li

doi:10.3390/toxins12120749

Abstract

Envenomation by viperid snakes may lead to severe bleeding, consumption coagulopathy, and thrombotic microangiopathy symptoms. The exact etiology or toxins responsible for thrombotic microangiopathy symptoms after snake envenomation remain obscure. Snake C-type lectin-like proteins (snaclecs) are one of the main non-enzymatic protein constituents in viper venoms, of which a majority are considered as modulators of thrombosis and hemostasis. In this study, we demonstrated that two snaclecs (mucetin and stejnulxin), isolated and identified from Protobothrops mucrosquamatus and Trimeresurus stejnegeri venoms, directly induced platelet degranulation and clot-retraction in vitro, and microvascular thrombosis has been confirmed in various organs in vivo. These snaclecs reduced cerebral blood flow and impaired motor balance and spatial memories in mice, which partially represent the thrombotic microangiopathy symptoms in some snakebite patients. The functional blocking of these snaclecs with antibodies alleviated the viper venom induced platelet activation and thrombotic microangiopathy-like symptoms. Understanding the pathophysiology of thrombotic microangiopathy associated with snake envenoming may lead to emerging therapeutic strategies.

Highlights

Envenomation and death caused by snakebites represent a significant public health problem worldwide, in tropical and subtropical areas
We demonstrate that mucetin and stejnulxin induce thrombotic microangiopathy (TMA)-like symptom characterized by multi-organ injuries and bleeding disorders with an acute consumption coagulopathy syndrome in a platelet-related way
Cobra venom mainly contains neurotoxins, while venoms from Viperidae mostly have hemorrhagic toxins, always inducing coagulopathy and platelet dysfunction, which may lead to bleeding disorders and multi-organ injuries [1,2,3,13]

Summary

Introduction

Envenomation and death caused by snakebites represent a significant public health problem worldwide, in tropical and subtropical areas. Snake venoms are mixtures of toxic and pharmacologically active peptides and proteins [4,5,6,7]. They are weapons for the snakes to immobilize or digest prey, and act as a defense against competitors and predators [8,9]. Envenomation by elapidae snakes may lead to shock and paralysis due to the neurotoxic components, such as the three-finger toxins and phospholipase A2, while viperid snakes may cause hemotoxic effects due to the varied roles of their toxins which include serine proteases, metalloproteases, disintegrins, and snake venom C-type lectins (snaclecs) [1,2,3,4,5,10,11,12]

Methods

Results

Conclusion