Potential Role of Platelet-Activating C-Type Lectin-Like Proteins in Viper Envenomation Induced Thrombotic Microangiopathy Symptom
Abstract
:1. Introduction
2. Results
2.1. Mucetin and Stejnulxin Induce Microthrombosis in Multiple Organ Tissues and Blood Biochemical Alterations in Mice
2.2. Mucetin and Stejnulxin Induce Cerebral Ischemia and Neurological Deficits in Mice
2.3. Mucetin and Stejnulxin Affect Blood Coagulation and Bleeding in Mice.
2.4. Mucetin and Stejnulxin Promote Platelet Activation and Clot Retraction.
2.5. Blocking Mucetin and Stejnulxin by Antibody Alleviate Crude Venom Induced TMA and Bleeding Disorders.
3. Discussion
4. Materials and Method
4.1. Tissue Preparation and Hematoxylin and Eosin (H&E) Staining
4.2. Real-Time Measurement of Cerebral Cortex Blood Flow
4.3. Rotarod Test
4.4. Morris Water Maze
4.5. Platelet Aggregation Assay
4.6. Membrane P-Selectin Detection
4.7. Clot Retraction
4.8. Plasma Coagulation Assay
4.9. Bleeding Assay
4.10. Generation and Purification of Polyclonal Antibodies against Mucetin and Stejnulxin
4.11. Statistical Analysi
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Warrell, D.A. Snake bite. Lancet 2010, 375, 77–88. [Google Scholar] [CrossRef]
- Alirol, E.; Sharma, S.K.; Bawaskar, H.S.; Kuch, U.; Chappuis, F. Snake bite in south asia: A review. Plos Neglect. Trop D 2010, 4, e603. [Google Scholar] [CrossRef] [Green Version]
- Gutierrez, J.M.; Calvete, J.J.; Habib, A.G.; Harrison, R.A.; Williams, D.J.; Warrell, D.A. Snakebite envenoming. Nat. Rev. Dis. Primers 2017, 3, 1–21. [Google Scholar] [CrossRef] [PubMed]
- Sanhajariya, S.; Isbister, G.K.; Duffull, S.B. The influence of the different disposition characteristics of snake toxins on the pharmacokinetics of snake venom. Toxins 2020, 12, 188. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Markland, F.S. Snake venoms and the hemostatic system. Toxicon 1998, 36, 1749–1800. [Google Scholar] [CrossRef]
- Tasoulis, T.; Isbister, G.K. A review and database of snake venom proteomes. Toxins 2017, 9, 290. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Waheed, H.F.; Moin, S.; Choudhary, M.I. Snake venom: From deadly toxins to life-saving therapeutics. Curr. Med. Chem. 2017, 24, 1874–1891. [Google Scholar] [CrossRef] [PubMed]
- Barlow, A.; Pook, C.E.; Harrison, R.A.; Wuster, W. Coevolution of diet and prey-specific venom activity supports the role of selection in snake venom evolution. P Roy. Soc. B Biol. Sci. 2009, 276, 2443–2449. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tian, H.; Liu, M.; Li, J.; Xu, R.; Long, C.; Li, H.; Mwangi, J.; Lu, Q.; Lai, R.; Shen, C. Snake c-type lectins potentially contribute to the prey immobilization in Protobothrops mucrosquamatus and Trimeresurus stejnegeri venoms. Toxins 2020, 12, 105. [Google Scholar] [CrossRef] [Green Version]
- Waiddyanatha, S.; Silva, A.; Siribaddana, S.; Isbister, G.K. Long-term effects of snake envenoming. Toxins 2019, 11, 193. [Google Scholar] [CrossRef] [Green Version]
- Mohamed Abd El-Aziz, T.; Soares, A.G.; Stockand, J.D. Snake venoms in drug discovery: Valuable therapeutic tools for life saving. Toxins 2019, 11, 564. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- White, J. Snake venoms and coagulopathy. Toxicon 2005, 45, 951–967. [Google Scholar] [CrossRef] [PubMed]
- Isbister, G.K. Snakebite doesn’t cause disseminated intravascular coagulation: Coagulopathy and thrombotic microangiopathy in snake envenoming. Semin. Thromb. Hemost. 2010, 36, 444–451. [Google Scholar] [CrossRef] [PubMed]
- Noutsos, T.; Currie, B.J.; Isbister, G.K. Snakebite associated thrombotic microangiopathy: A protocol for the systematic review of clinical features, outcomes, and role of interventions. Syst. Rev. 2019, 8, 212. [Google Scholar] [CrossRef] [Green Version]
- Isbister, G.K.; Little, M.; Cull, G.; McCoubrie, D.; Lawton, P.; Szabo, F.; Kennedy, J.; Trethewy, C.; Luxton, G.; Brown, S. Thrombotic microangiopathy from australian brown snake (pseudonaja) envenoming. Intern. Med. J. 2007, 37, 523–528. [Google Scholar] [CrossRef]
- Tan, C.H.; Tan, K.Y.; Ng, T.S.; Quah, E.S.H.; Ismail, A.K.; Khomvilai, S.; Sitprija, V.; Tan, N.H. Venomics of trimeresurus (popeia) nebularis, the cameron highlands pit viper from malaysia: Insights into venom proteome, toxicity and neutralization of antivenom. Toxins 2019, 11, 95. [Google Scholar] [CrossRef] [Green Version]
- Patra, A.; Kalita, B.; Chanda, A.; Mukherjee, A.K. Proteomics and antivenomics of echis carinatus carinatus venom: Correlation with pharmacological properties and pathophysiology of envenomation. Sci. Rep. 2017, 7, 1–7. [Google Scholar] [CrossRef] [Green Version]
- Abidin, S.A.Z.; Rajadurai, P.; Chowdhury, M.E.H.; Rusmili, M.R.A.; Othman, I.; Naidu, R. Proteomic characterization and comparison of malaysian tropidolaemus wagleri and cryptelytrops purpureomaculatus venom using shotgun-proteomics. Toxins 2016, 8, 299. [Google Scholar]
- Tan, K.Y.; Tan, N.H.; Tan, C.H. Venom proteomics and antivenom neutralization for the chinese eastern russell’s viper, daboia siamensis from guangxi and taiwan. Sci. Rep. 2018, 8, 1–4. [Google Scholar] [CrossRef]
- Eble, J.A. Structurally robust and functionally highly versatile-c-type lectin (-related) proteins in snake venoms. Toxins 2019, 11, 136. [Google Scholar] [CrossRef] [Green Version]
- Tsai, I.H.; Chen, Y.H.; Wang, Y.M.; Liau, M.Y.; Lu, P.J. Differential expression and geographic variation of the venom phospholipases a(2) of Calloselasma rhodostoma and Trimeresurus mucrosquamatus. Arch. Biochem Biophys 2001, 387, 257–264. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tsai, I.H.; Wang, Y.M.; Chen, Y.H.; Tsai, T.S.; Tu, M.C. Venom phospholipases a(2) of bamboo viper (Trimeresurus stejnegeri): Molecular characterization, geographic variations and evidence of multiple ancestries. Biochem. J. 2004, 377, 215–223. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lin, C.-C.; Chen, Y.-C.; Goh, Z.N.L.; Seak, C.-K.; Seak, J.C.-Y.; Shi-Ying, G.; Seak, C.-J. Wound infections of snakebites from the venomous Protobothrops mucrosquamatus and Viridovipera stejnegeri in taiwan: Bacteriology, antibiotic susceptibility, and predicting the need for antibiotics—A bite study. Toxins 2020, 12, 575. [Google Scholar] [CrossRef]
- Lu, Q.M.; Navdaev, A.; Clemetson, J.M.; Clemetson, K.J. Gpib is involved in platelet aggregation induced by mucetin, a snake c-type lectin protein from chinese habu (Trimeresurus mucrosquamatus) venom. Thromb. Haemost. 2004, 91, 1168–1176. [Google Scholar] [CrossRef] [PubMed]
- Lee, W.H.; Du, X.Y.; Lu, Q.M.; Clemetson, K.J.; Zhang, Y. Stejnulxin, a novel snake c-type lectin-like protein from Trimeresurus stejnegeri venom is a potent platelet agonist acting specifically via gpvl. Thromb. Haemostasis 2003, 90, 662–671. [Google Scholar] [CrossRef] [Green Version]
- Zheng, L.; Zhang, D.; Cao, W.; Song, W.-C.; Zheng, X. Synergistic effects of adamts13 deficiency and complement activation in pathogenesis of thrombotic microangiopathy. Blood 2019, 134, 1095–1105. [Google Scholar] [CrossRef]
- Boviatsis, E.J.; Kouyialis, A.T.; Papatheodorou, G.; Gavra, M.; Korfias, S.; Sakas, D.E. Multiple hemorrhagic brain infarcts after viper envenomation. Am. J. Trop Med. Hyg. 2003, 68, 253–257. [Google Scholar] [CrossRef]
- Murthy, J.M.K.; Kishore, L.T.; Naidu, K.S. Cerebral infarction after envenomation by viper. J. Comput Assist. Tomo. 1997, 21, 35–37. [Google Scholar] [CrossRef]
- Jeevagan, V.; Chang, T.; Gnanathasan, C.A. Acute ischemic stroke following hump-nosed viper envenoming; first authenticated case. Thromb. J. 2012, 10, 21. [Google Scholar] [CrossRef] [Green Version]
- Panicker, J.N.; Madhusudanan, S. Cerebral infarction in a young male following viper envenomation. J. Assoc. Physicians India 2000, 48, 744–745. [Google Scholar]
- Del Brutto, O.H.; Del Brutto, V.J. Neurological complications of venomous snake bites: A review. Acta Neurol. Scand. 2012, 125, 363–372. [Google Scholar] [CrossRef] [PubMed]
- Malbranque, S.; Piercecchi-Marti, M.D.; Thomas, L.; Barbey, C.; Courcier, D.; Bucher, B.; Ridarch, A.; Smadja, D.; Warrell, D.A. Fatal diffuse thrombotic microangiopathy after a bite by the "fer-de-lance" pit viper (bothrops lanceolatus) of martinique. Am. J. Trop. Med. Hyg. 2008, 78, 856–861. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zeng, X.; Hu, J.; Liang, X.; Wu, Y.; Yan, M.; Zhu, M.; Fu, Y. Acute cerebral infarction following a trimeresurus stejnegeri snakebite: A case report. Medicine 2019, 98, e15684. [Google Scholar] [CrossRef] [PubMed]
- Dirnagl, U.; Iadecola, C.; Moskowitz, M.A. Pathobiology of ischaemic stroke: An integrated view. Trends Neurosci. 1999, 22, 391–397. [Google Scholar] [CrossRef]
- Clemetson, K.J. Snaclecs (snake c-type lectins) that inhibit or activate platelets by binding to receptors. Toxicon 2010, 56, 1236–1246. [Google Scholar] [CrossRef]
- Lei, X.; Reheman, A.; Hou, Y.; Zhou, H.; Wang, Y.M.; Marshall, A.H.; Liang, C.F.; Dai, X.R.; Li, B.X.; Vanhoorelbeke, K.; et al. Anfibatide, a novel gpib complex antagonist, inhibits platelet adhesion and thrombus formation in vitro and in vivo in murine models of thrombosis. Thromb. Haemostasis 2014, 111, 279–289. [Google Scholar]
- Vaiyapuri, S.; Hutchinson, E.G.; Ali, M.S.; Dannoura, A.; Stanley, R.G.; Harrison, R.A.; Bicknell, A.B.; Gibbins, J.M. Rhinocetin, a venom-derived integrin-specific antagonist inhibits collagen-induced platelet and endothelial cell functions. J. Biol. Chem. 2012, 287, 26235–26244. [Google Scholar] [CrossRef] [Green Version]
- Chong, B.H.; Murray, B.; Berndt, M.C.; Dunlop, L.C.; Brighton, T.; Chesterman, C.N. Plasma p-selectin is increased in thrombotic consumptive platelet disorders. Blood 1994, 83, 1535–1541. [Google Scholar] [CrossRef] [Green Version]
- Kim, O.V.; Litvinov, R.I.; Alber, M.S.; Weisel, J.W. Quantitative structural mechanobiology of platelet-driven blood clot contraction. Nat. Commun. 2017, 8, 1–10. [Google Scholar] [CrossRef]
- Li, B.; Silva, J.R.; Lu, X.; Luo, L.; Wang, Y.; Xu, L.; Aierken, A.; Shynykul, Z.; Kamau, P.M.; Luo, A.; et al. Molecular game theory for a toxin-dominant food chain model. Natl. Sci. Rev. 2019, 6, 1191–1200. [Google Scholar] [CrossRef] [Green Version]
- Yang, S.; Wang, Y.; Wang, L.; Kamau, P.; Zhang, H.; Luo, A.; Lu, X.; Lai, R. Target switch of centipede toxins for antagonistic switch. Sci. Adv. 2020, 6, eabb5734. [Google Scholar] [CrossRef]
- Lu, Q.M.; Navdaev, A.; Clemetson, J.M.; Clemetson, K.J. Snake venom c-type lectins interacting with platelet receptors. Structure-function relationships and effects on haemostasis. Toxicon 2005, 45, 1089–1098. [Google Scholar] [CrossRef]
- Maduwage, K.; Isbister, G.K. Current treatment for venom-induced consumption coagulopathy resulting from snakebite. PLoS Neglect. Trop Dis. 2014, 8, e3220. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Park, E.J.; Choi, S.; Kim, H.-H.; Jung, Y.S. Novel treatment strategy for patients with venom-induced consumptive coagulopathy from a pit viper bite. Toxins 2020, 12, 295. [Google Scholar] [CrossRef] [PubMed]
- Wedasingha, S.; Isbister, G.; Silva, A. Bedside coagulation tests in diagnosing venom-induced consumption coagulopathy in snakebite. Toxins 2020, 12, 583. [Google Scholar] [CrossRef]
- Withana, M.; Rodrigo, C.; Gnanathasan, A.; Gooneratne, L. Presumptive thrombotic thrombocytopenic purpura following a hump-nosed viper (Hypnale hypnale) bite: A case report. J. Venom. Anim. Toxins 2014, 20, 26. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dineshkumar, T.; Dhanapriya, J.; Sakthirajan, R.; Thirumalvalavan, K.; Kurien, A.A.; Balasubramaniyan, T.; Gopalakrishnan, N. Thrombotic microangiopathy due to viperidae bite: Two case reports. Indian J. Nephrol. 2017, 27, 161–164. [Google Scholar]
- Gn, Y.M.; Ponnusamy, A.; Thimma, V. Snakebite induced thrombotic microangiopathy leading to renal cortical necrosis. Case Rep. Nephrol. 2017, 2017, 1348749. [Google Scholar] [CrossRef] [Green Version]
- Rathnayaka, R.M.M.K.N.; Ranathunga, P.E.A.N.; Kularatne, S.A.M. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura following hump-nosed pit viper (genus: Hypnale) envenoming in sri lanka. Wild Environ. Med. 2019, 30, 66–78. [Google Scholar] [CrossRef] [Green Version]
- Whitfield, J.B. Gamma glutamyl transferase. Crit. Rev. Clin. Lab. Sci. 2001, 38, 263–355. [Google Scholar] [CrossRef]
- Rantala, A.O.; Lilja, M.; Kauma, H.; Savolainen, M.J.; Reunanen, A.; Kesaniemi, Y.A. Gamma-glutamyl transpeptidase and the metabolic syndrome. J. Intern. Med. 2000, 248, 230–238. [Google Scholar] [CrossRef] [PubMed]
- Heemskerk, J.; Mattheij, N.; Cosemans, J. Platelet-based coagulation: Different populations, different functions. J. Thromb. Haemost 2013, 11, 2–16. [Google Scholar] [CrossRef] [PubMed]
- Xu, X.R.; Zhang, D.; Oswald, B.E.; Carrim, N.; Wang, X.; Hou, Y.; Zhang, Q.; Lavalle, C.; McKeown, T.; Marshall, A.H.; et al. Platelets are versatile cells: New discoveries in hemostasis, thrombosis, immune responses, tumor metastasis and beyond. Crit. Rev. Clin. Lab. Sci. 2016, 53, 409–430. [Google Scholar] [CrossRef] [PubMed]
- Sadler, J.E. Von willebrand factor, adamts13, and thrombotic thrombocytopenic purpura. Blood 2008, 112, 11–18. [Google Scholar] [CrossRef] [Green Version]
- Shenkman, B.; Einav, Y. Thrombotic thrombocytopenic purpura and other thrombotic microangiopathic hemolytic anemias: Diagnosis and classification. Autoimmun. Rev. 2014, 13, 584–586. [Google Scholar] [CrossRef]
- Chen, J.; Reheman, A.; Gushiken, F.C.; Nolasco, L.; Fu, X.; Moake, J.L.; Ni, H.; López, J.A. N-acetylcysteine reduces the size and activity of von willebrand factor in human plasma and mice. J. Clin. Investig. 2011, 121, 593–603. [Google Scholar] [CrossRef] [Green Version]
- Wei, Q.; Lu, Q.M.; Jin, Y.; Li, R.; Wei, J.F.; Wang, W.Y.; Xiong, Y.L. Purification and cloning of a novel c-type lectin-like protein with platelet aggregation activity from trimeresurus mucrosquamatus venom. Toxicon 2002, 40, 1331–1338. [Google Scholar] [CrossRef]
- Tai, H.; Wei, Q.; Jin, Y.; Su, M.; Song, J.X.; Zhou, X.D.; Ouyang, H.M.; Wang, W.Y.; Xiong, Y.L.; Zhang, Y. Tmva, a snake c-type lectin-like protein from trimeresurus mucrosquamatus venom, activates platelet via gpib. Toxicon 2004, 44, 649–656. [Google Scholar] [CrossRef]
- Padilla, A.; Moake, J.L.; Bernardo, A.; Ball, C.; Wang, Y.T.; Arya, M.; Nolasco, L.; Turner, N.; Berndt, M.C.; Anvari, B.; et al. P-selectin anchors newly released ultralarge von willebrand factor multimers to the endothelial cell surface. Blood 2004, 103, 2150–2156. [Google Scholar] [CrossRef] [Green Version]
- Kunitada, S.; Fitzgerald, G.A.; Fitzgerald, D.J. Inhibition of clot lysis and decreased binding of tissue-type plasminogen-activator as a consequence of clot retraction. Blood 1992, 79, 1420–1427. [Google Scholar] [CrossRef] [Green Version]
- Chung, C.-H.; Wu, W.-B.; Huang, T.-F. Aggretin, a snake venom–derived endothelial integrin α2β1 agonist, induces angiogenesis via expression of vascular endothelial growth factor. Blood 2004, 103, 2105–2113. [Google Scholar] [CrossRef] [PubMed]
- He, X.Q.; Shen, C.B.; Lu, Q.M.; Li, J.; Wei, Y.Q.; He, L.; Bai, R.Z.; Zheng, J.; Luan, N.; Zhang, Z.Y.; et al. Prokineticin 2 plays a pivotal role in psoriasis. Ebiomedicine 2016, 13, 248–261. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yu, C.L.; Zhou, H.; Chai, A.P.; Yang, Y.X.; Mao, R.R.; Xu, L. Whole-scale neurobehavioral assessments of photothrombotic ischemia in freely moving mice. J. Neurosci. Meth. 2015, 239, 100–107. [Google Scholar] [CrossRef] [PubMed]
- Duan, T.T.; Tan, J.W.; Yuan, Q.; Cao, J.; Zhou, Q.X.; Xu, L. Acute ketamine induces hippocampal synaptic depression and spatial memory impairment through dopamine d1/d5 receptors. Psychopharmacology 2013, 228, 451–461. [Google Scholar] [CrossRef]
- Shen, C.; Liu, M.; Tian, H.; Li, J.; Xu, R.; Mwangi, J.; Lu, Q.; Hao, X.; Lai, R. Conformation-specific blockade of αiibβ3 by a non-rgd peptide to inhibit platelet activation without causing significant bleeding and thrombocytopenia. Thromb. Haemostasis 2020, 120, 1432–1441. [Google Scholar] [CrossRef]
- Xu, X.R.; Wang, Y.; Adili, R.; Ju, L.; Spring, C.M.; Jin, J.W.; Yang, H.; Neves, M.A.; Chen, P.; Yang, Y.; et al. Apolipoprotein a-iv binds αiibβ3 integrin and inhibits thrombosis. Nat. Commun. 2018, 9, 3608. [Google Scholar] [CrossRef] [Green Version]
- Shen, C.; Liu, M.; Xu, R.; Wang, G.; Li, J.; Chen, P.; Ma, W.; Mwangi, J.; Lu, Q.; Duan, Z.; et al. The 14-3-3ζ–c-src–integrin-β3 complex is vital for platelet activation. Blood 2020, 136, 974–988. [Google Scholar] [CrossRef]
- Tang, X.; Fang, M.; Cheng, R.; Zhang, Z.; Wang, Y.; Shen, C.; Han, Y.; Lu, Q.; Du, Y.; Liu, Y.; et al. Iron-deficiency and estrogen are associated with ischemic stroke by up-regulating transferrin to induce hypercoagulability. Circ. Res. 2020, 127, 651–663. [Google Scholar] [CrossRef]
- Zhang, Z.; Meng, P.; Han, Y.; Shen, C.; Li, B.; Hakim, M.A.; Zhang, X.; Lu, Q.; Rong, M.; Lai, R. Mitochondrial DNA-ll-37 complex promotes atherosclerosis by escaping from autophagic recognition. Immunity 2015, 43, 1137–1147. [Google Scholar] [CrossRef] [Green Version]
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Long, C.; Liu, M.; Tian, H.; Li, Y.; Wu, F.; Mwangi, J.; Lu, Q.; Mohamed Abd El-Aziz, T.; Lai, R.; Shen, C. Potential Role of Platelet-Activating C-Type Lectin-Like Proteins in Viper Envenomation Induced Thrombotic Microangiopathy Symptom. Toxins 2020, 12, 749. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120749
Long C, Liu M, Tian H, Li Y, Wu F, Mwangi J, Lu Q, Mohamed Abd El-Aziz T, Lai R, Shen C. Potential Role of Platelet-Activating C-Type Lectin-Like Proteins in Viper Envenomation Induced Thrombotic Microangiopathy Symptom. Toxins. 2020; 12(12):749. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120749
Chicago/Turabian StyleLong, Chengbo, Ming Liu, Huiwen Tian, Ya Li, Feilong Wu, James Mwangi, Qiumin Lu, Tarek Mohamed Abd El-Aziz, Ren Lai, and Chuanbin Shen. 2020. "Potential Role of Platelet-Activating C-Type Lectin-Like Proteins in Viper Envenomation Induced Thrombotic Microangiopathy Symptom" Toxins 12, no. 12: 749. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120749