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
Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysuru 570006, India.
Department of Studies and Research in Biochemistry, Tumkur University, Tumkuru 572103, India.
Nat Commun. 2016 Apr 19;7:11361. 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.
印度锯鳞蝰蛇咬伤会导致咬伤部位持续的组织破坏。中性粒细胞是早期防御过程中的主要白细胞，会在咬伤部位聚集。在此我们表明，锯鳞蝰蛇毒液会诱导中性粒细胞胞外陷阱（NET）形成。NET会阻塞血管并将毒液毒素困在注射部位，从而促进组织破坏。NET的稳定性归因于锯鳞蝰蛇毒液中缺乏降解NET的DNase活性。在小鼠尾巴模型中，同时注射毒液和DNase 1的小鼠，以及注射毒液的中性粒细胞减少的小鼠，在注射部位均未出现NET、毒液积累和组织破坏。令人惊讶的是，随后注射DNase 1也可防止毒液诱导的小鼠尾巴组织破坏。因此，我们的研究表明，DNase 1治疗可能具有预防蛇毒所致组织破坏的治疗潜力。
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