title: TMVA, a snake C-type lectin-like protein from Trimeresurus mucrosquamatus venom, activates platelet via GPIb.
abstract: TMVA is a C-type lectin-like protein with potent platelet activating activity from Trimeresurus mucrosquamatus venom. In the absence of von Willebrand factor (vWF), TMVA dose-dependently induced aggregation of washed platelets. Anti-GP Ib monoclonal antibodies (mAbs), HIP1, specifically inhibited TMVA-induced aggregation in a dose-dependent manner. The aggregation was also inhibited by mAb P2 (an anti-GP IIb mAb). Flow cytometric analysis revealed that FITC-TMVA bound to human formalin-fixed platelets in a saturable manner, and its binding was specifically blocked by HIP1 in a dose-dependent manner. Flow cytometric analysis showed that TMVA did not bind to platelet GPIX, GPIIb, GPIIIa, GPIa, GPIIa and GPIV. Moreover, the platelet aggregation induced by TMVA was partially inhibited when platelet was pretreated with mocarhagin, a snake venom protease that specifically cleaves human GPIb. These results suggest that TMVA is a strong platelet agonist via GPIb and it might have multiple functional binding-sites on GPIb molecule or on other unknown receptor.
authors.affiliation: Department of Animal Toxinology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Tai
authors.forename: Qin
authors.initials: Q
authors.lastname: Wei
authors.forename: Yang
authors.initials: Y
authors.lastname: Jin
authors.forename: Min
authors.initials: M
authors.lastname: Su
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Song
authors.forename: Xin-Ding
authors.initials: XD
authors.lastname: Zhou
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Ouyang
authors.forename: Wan-Yu
authors.initials: WY
authors.lastname: Wang
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Xiong
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003435:Crotalid Venoms / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D008666:Metalloendopeptidases / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000378:metabolism / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D017841:Trimeresurus; D014757:Viper Venoms / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D003435:Crotalid Venoms; D037181:Lectins, C-Type; D010972:Platelet Activating Factor; D019038:Platelet Glycoprotein GPIb-IX Complex; C468283:TMVA protein, Trimeresurus mucrosquamatus; C029748:Trimeresurus venoms; D014757:Viper Venoms; D008666:Metalloendopeptidases; C099092:mocarhagin; D016650:Fluorescein-5-isothiocyanate