TMVA, a snake C-type lectin-like protein from Trimeresurus mucrosquamatus venom, activates platelet via GPIb.
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.
Tai
Hong
H
Department of Animal Toxinology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, People's Republic of China.
Wei
Qin
Q
Jin
Yang
Y
Su
Min
M
Song
Jian-Xin
JX
Zhou
Xin-Ding
XD
Ouyang
Hong-Mei
HM
Wang
Wan-Yu
WY
Xiong
Yu-Liang
YL
Zhang
Yun
Y
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*
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