Potential Role of Platelet-Activating C-Type Lectin-Like Proteins in Viper Envenomation Induced Thrombotic Microangiopathy Symptom
Chengbo Long,
Ming Liu,
Huiwen Tian,
Ya Li,
Feilong Wu,
James Mwangi,
Qiumin Lu,
Tarek Mohamed Abd El-Aziz,
Ren Lai,
Chuanbin Shen
Affiliations
Chengbo Long
Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human, Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
Ming Liu
Department of Molecular and Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
Huiwen Tian
Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human, Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
Ya Li
Key Laboratory of Laboratory Medicine of Yunnan Province/Department of Clinical Laboratory, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
Feilong Wu
Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human, Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
James Mwangi
Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human, Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
Qiumin Lu
Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human, Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
Tarek Mohamed Abd El-Aziz
Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA
Ren Lai
Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human, Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
Chuanbin Shen
Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human, Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
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.
