Platelet Desialylation Is a Novel Mechanism and Therapeutic Target in <i>Daboia siamensis</i> and <i>Agkistrodon halys</i> Envenomation-Induced Thrombocytopenia
Venom-induced thrombocytopenia (VIT) is one of the most important hemotoxic effects of a snakebite, which is often associated with venom-induced consumptive coagulopathy (VICC). Refractory thrombocytopenia without significant coagulation abnormalities has also been reported after envenomation by som...
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MDPI AG
2022-11-01
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| author | Cheng Zhang Zhanfeng Zhang Enyu Liang Yunlong Gao Hui Li Fangfang Xu Weiye Chen Ming Liu Xianzhang Huang |
| author_facet | Cheng Zhang Zhanfeng Zhang Enyu Liang Yunlong Gao Hui Li Fangfang Xu Weiye Chen Ming Liu Xianzhang Huang |
| author_sort | Cheng Zhang |
| collection | DOAJ |
| description | Venom-induced thrombocytopenia (VIT) is one of the most important hemotoxic effects of a snakebite, which is often associated with venom-induced consumptive coagulopathy (VICC). Refractory thrombocytopenia without significant coagulation abnormalities has also been reported after envenomation by some viperid snakes; however, the mechanisms are not well understood and therapeutic strategies are lacking. Here, we found that patients injured by <i>Daboia siamensis</i> or <i>Agkistrodon halys</i> snakes, who were resistant to standard antivenom treatment, had developed coagulopathy-independent thrombocytopenia. Venoms from these viperid snakes, rather than from the elapid snake (<i>Bungarus multicinctus</i>), induced platelet surface expression of neuraminidase-1 (NEU-1), and significantly increased the desialylation of the glycoproteins on human platelets. The desialylated platelets caused by viperid snake venoms were further internalized by macrophages, which resulted in reduced platelet numbers in peripheral blood. Importantly, neuraminidase inhibitor significantly decreased viper venom-induced platelet desialylation, therefore inhibiting platelet phagocytosis by macrophages, and alleviating venom-induced thrombocytopenia. Collectively, these findings support an important role for desialylated platelet clearance in the progression of viper envenomation-induced, coagulopathy-independent thrombocytopenia. Our study demonstrates that the neuraminidase inhibitor may be a potential therapy or adjuvant therapy to treat snakebite-induced thrombocytopenia. |
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| spelling | doaj.art-fa70cd14bc694d30b386475f2a13c3b82023-11-24T09:21:01ZengMDPI AGMolecules1420-30492022-11-012722777910.3390/molecules27227779Platelet Desialylation Is a Novel Mechanism and Therapeutic Target in <i>Daboia siamensis</i> and <i>Agkistrodon halys</i> Envenomation-Induced ThrombocytopeniaCheng Zhang0Zhanfeng Zhang1Enyu Liang2Yunlong Gao3Hui Li4Fangfang Xu5Weiye Chen6Ming Liu7Xianzhang Huang8Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, ChinaClinical Laboratory, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, ChinaDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, ChinaDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, ChinaDepartment of Hematology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, ChinaThe Second Clinical School of Medicine Medicial College, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, ChinaSchool of Life Sciences, University of Science and Technology of China, Hefei 230027, ChinaDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, ChinaVenom-induced thrombocytopenia (VIT) is one of the most important hemotoxic effects of a snakebite, which is often associated with venom-induced consumptive coagulopathy (VICC). Refractory thrombocytopenia without significant coagulation abnormalities has also been reported after envenomation by some viperid snakes; however, the mechanisms are not well understood and therapeutic strategies are lacking. Here, we found that patients injured by <i>Daboia siamensis</i> or <i>Agkistrodon halys</i> snakes, who were resistant to standard antivenom treatment, had developed coagulopathy-independent thrombocytopenia. Venoms from these viperid snakes, rather than from the elapid snake (<i>Bungarus multicinctus</i>), induced platelet surface expression of neuraminidase-1 (NEU-1), and significantly increased the desialylation of the glycoproteins on human platelets. The desialylated platelets caused by viperid snake venoms were further internalized by macrophages, which resulted in reduced platelet numbers in peripheral blood. Importantly, neuraminidase inhibitor significantly decreased viper venom-induced platelet desialylation, therefore inhibiting platelet phagocytosis by macrophages, and alleviating venom-induced thrombocytopenia. Collectively, these findings support an important role for desialylated platelet clearance in the progression of viper envenomation-induced, coagulopathy-independent thrombocytopenia. Our study demonstrates that the neuraminidase inhibitor may be a potential therapy or adjuvant therapy to treat snakebite-induced thrombocytopenia.https://www.mdpi.com/1420-3049/27/22/7779snake venomplateletmacrophagethrombocytopeniadesialylationneuraminidase |
| spellingShingle | Cheng Zhang Zhanfeng Zhang Enyu Liang Yunlong Gao Hui Li Fangfang Xu Weiye Chen Ming Liu Xianzhang Huang Platelet Desialylation Is a Novel Mechanism and Therapeutic Target in <i>Daboia siamensis</i> and <i>Agkistrodon halys</i> Envenomation-Induced Thrombocytopenia Molecules snake venom platelet macrophage thrombocytopenia desialylation neuraminidase |
| title | Platelet Desialylation Is a Novel Mechanism and Therapeutic Target in <i>Daboia siamensis</i> and <i>Agkistrodon halys</i> Envenomation-Induced Thrombocytopenia |
| title_full | Platelet Desialylation Is a Novel Mechanism and Therapeutic Target in <i>Daboia siamensis</i> and <i>Agkistrodon halys</i> Envenomation-Induced Thrombocytopenia |
| title_fullStr | Platelet Desialylation Is a Novel Mechanism and Therapeutic Target in <i>Daboia siamensis</i> and <i>Agkistrodon halys</i> Envenomation-Induced Thrombocytopenia |
| title_full_unstemmed | Platelet Desialylation Is a Novel Mechanism and Therapeutic Target in <i>Daboia siamensis</i> and <i>Agkistrodon halys</i> Envenomation-Induced Thrombocytopenia |
| title_short | Platelet Desialylation Is a Novel Mechanism and Therapeutic Target in <i>Daboia siamensis</i> and <i>Agkistrodon halys</i> Envenomation-Induced Thrombocytopenia |
| title_sort | platelet desialylation is a novel mechanism and therapeutic target in i daboia siamensis i and i agkistrodon halys i envenomation induced thrombocytopenia |
| topic | snake venom platelet macrophage thrombocytopenia desialylation neuraminidase |
| url | https://www.mdpi.com/1420-3049/27/22/7779 |
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