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Shen C, Liu M, Mackeigan DT, et al. Viper venoms drive the macrophages and hepatocytes to sequester and clear platelets: novel mechanism and therapeutic strategy for venom-induced thrombocytopenia. Arch Toxicol. 2021;95(11):3589-3599doi: 10.1007/s00204-021-03154-5.
Shen, C., Liu, M., Mackeigan, D. T., Chen, Z. Y., Chen, P., Karakas, D., Li, J., Norris, P. A. A., Li, J., Deng, Y., Long, C., Lai, R., & Ni, H. (2021). Viper venoms drive the macrophages and hepatocytes to sequester and clear platelets: novel mechanism and therapeutic strategy for venom-induced thrombocytopenia. Archives of toxicology, 95(11), 3589-3599. https://doi.org/10.1007/s00204-021-03154-5
Shen, Chuanbin, et al. "Viper venoms drive the macrophages and hepatocytes to sequester and clear platelets: novel mechanism and therapeutic strategy for venom-induced thrombocytopenia." Archives of toxicology vol. 95,11 (2021): 3589-3599. doi: https://doi.org/10.1007/s00204-021-03154-5
Shen C, Liu M, Mackeigan DT, Chen ZY, Chen P, Karakas D, Li J, Norris PAA, Li J, Deng Y, Long C, Lai R, Ni H. Viper venoms drive the macrophages and hepatocytes to sequester and clear platelets: novel mechanism and therapeutic strategy for venom-induced thrombocytopenia. Arch Toxicol. 2021 Nov;95(11):3589-3599. doi: 10.1007/s00204-021-03154-5. Epub 2021 Sep 14. PMID: 34519865.
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Arch Toxicol. 2021 Nov;95(11):3589-3599. doi: 10.1007/s00204-021-03154-5. Epub 2021 Sep 14.

Viper venoms drive the macrophages and hepatocytes to sequester and clear platelets: novel mechanism and therapeutic strategy for venom-induced thrombocytopenia.

Archives of toxicology

Chuanbin Shen, Ming Liu, Daniel Thomas Mackeigan, Zi Yan Chen, Pingguo Chen, Danielle Karakas, June Li, Peter A A Norris, Jiayao Li, Yanling Deng, Chengbo Long, Ren Lai, Heyu Ni

Affiliations

  1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5S 1A1, Canada.
  2. Department of Laboratory Medicine, LKSKI-Keenan Research Centre for Biomedical Science, St. Michael's Hospital, and Toronto Platelet Immunobiology Group, Toronto, ON, M5B 1W8, Canada.
  3. Department of Molecular and Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, Anhui, China.
  4. Department of Physiology, University of Toronto, Toronto, ON, M5S 1A1, Canada.
  5. Canadian Blood Services Centre for Innovation, Toronto, ON, M5G 2M1, Canada.
  6. Hospital of Traditional Chinese Medicine of Wuzhou City, Wuzhou, 543002, Guangxi, China.
  7. 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, Kunming, 650223, Yunnan, China.
  8. KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, Yunnan, China.
  9. 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, Kunming, 650223, Yunnan, China. [email protected].
  10. KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, Yunnan, China. [email protected].
  11. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5S 1A1, Canada. [email protected].
  12. Department of Laboratory Medicine, LKSKI-Keenan Research Centre for Biomedical Science, St. Michael's Hospital, and Toronto Platelet Immunobiology Group, Toronto, ON, M5B 1W8, Canada. [email protected].
  13. Department of Physiology, University of Toronto, Toronto, ON, M5S 1A1, Canada. [email protected].
  14. Canadian Blood Services Centre for Innovation, Toronto, ON, M5G 2M1, Canada. [email protected].
  15. Department of Medicine, University of Toronto, Toronto, ON, M5S 1A1, Canada. [email protected].
  16. Department of Laboratory Medicine and Pathobiology, Department of Medicine and Department of Physiology, University of TorontoCanadian Blood Services Centre for Innovation, St. Michael's Hospital, Room 421, LKSKI - Keenan Research Centre, 209 Victoria Street, Toronto, ON, M5B 1W8, Canada. [email protected].

PMID: 34519865 DOI: 10.1007/s00204-021-03154-5

Abstract

Venomous snakebites cause clinical manifestations that range from local to systemic and are considered a significant global health challenge. Persistent or refractory thrombocytopenia has been frequently reported in snakebite patients, especially in cases caused by viperidae snakes. Viper envenomation-induced thrombocytopenia may persist in the absence of significant consumption coagulopathy even after the antivenom treatment, yet the mechanism remains largely unknown. Our study aims to investigate the mechanism and discover novel therapeutic targets for coagulopathy-independent thrombocytopenia caused by viper envenomation. Here we found that patients bitten by Protobothrops mucrosquamatus and Trimeresurus stejnegeri, rather than Naja. atra may develop antivenom-resistant and coagulopathy-independent thrombocytopenia. Crude venoms and the derived C-type lectin-like proteins from these vipers significantly increased platelet surface expression of neuraminidase and platelet desialylation, therefore led to platelet ingestion by both macrophages and hepatocytes in vitro, and drastically decreased peripheral platelet counts in vivo. Our study is the first to demonstrate that desialylation-mediated platelet clearance is a novel mechanism of viper envenomation-induced refractory thrombocytopenia and C-type lectin-like proteins derived from the viper venoms contribute to snake venom-induced thrombocytopenia. The results of this study suggest the inhibition of platelet desialylation as a novel therapeutic strategy against viper venom-induced refractory thrombocytopenia.

© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Keywords: Hepatocyte; Macrophage; Platelet desialylation; Snake venom; Thrombocytopenia

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