NETosis and lack of DNase activity are key factors in Echis carinatus venom-induced tissue destruction

• Published in: Nature communications 2016-04, Vol.7 (1), p.11361-11361, Article 11361
• Main Authors: Katkar, Gajanan D., Sundaram, Mahalingam S., NaveenKumar, Somanathapura K., Swethakumar, Basavarajaiah, Sharma, Rachana D., Paul, Manoj, Vishalakshi, Gopalapura J., Devaraja, Sannaningaiah, Girish, Kesturu S., Kemparaju, Kempaiah
• Format: Article
• Language: English
• Subjects: 14/1; 14/19; 14/28; 14/34; 14/63; 631/250/1933; 631/250/2504/223/1699; 631/45/173; 64/60; 692/308; 82; 82/1; 82/16; 82/29; 82/51; 82/80; 82/83; Animals; Antidotes - metabolism; Antidotes - pharmacology; Deoxyribonuclease I - metabolism; Deoxyribonuclease I - pharmacology; Extracellular Traps - drug effects; Extracellular Traps - immunology; Female; Humanities and Social Sciences; Injections, Intralesional; Male; Mice; multidisciplinary; Necrosis - chemically induced; Necrosis - pathology; Necrosis - prevention & control; Neutropenia - immunology; Neutrophils - cytology; Neutrophils - immunology; Protective Factors; Science; Tail - drug effects; Tail - immunology; Tail - pathology; Viper Venoms - administration & dosage; Viper Venoms - antagonists & inhibitors; Viper Venoms - toxicity; Viperidae - physiology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11361

Indian Echis carinatus bite causes sustained tissue destruction at the bite site. Neutrophils, the major leukocytes in the early defence process, accumulate at the bite site. Here we show that E. carinatus venom induces neutrophil extracellular trap (NET) formation. The NETs block the blood vessels and entrap the venom toxins at the injection site, promoting tissue destruction. The stability of NETs is attributed to the lack of NETs-degrading DNase activity in E. carinatus venom. In a mouse tail model, mice co-injected with venom and DNase 1, and neutropenic mice injected with the venom, do not develop NETs, venom accumulation and tissue destruction at the injected site. Strikingly, venom-induced mice tail tissue destruction is also prevented by the subsequent injection of DNase 1. Thus, our study suggests that DNase 1 treatment may have a therapeutic potential for preventing the tissue destruction caused by snake venom. The saw-scaled viper venom causes continued tissue damage that may cause death. Here the authors show that the venom attracts neutrophils to the bite site and induces neutrophil extracellular traps that capture venom components causing tissue damage, which can be prevented by enzymatic DNA degradation.