Abstract
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.
Highlights
Indian Echis carinatus bite causes sustained tissue destruction at the bite site
We show that the venom-stimulated neutrophils undergo NETosis and that the resulting neutrophil extracellular trap (NET) block the blood vessels to prevent the venom from entering the circulation, resulting in venom accumulation and tissue destruction at the injection site
Our study suggests that E. carinatus venom stimulated the neutrophils to undergo NETosis both in vitro and in vivo
Summary
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. Studies have demonstrated that Metzincin family matrix-degrading snake venom metalloproteases (SVMPs)[5] and hyaluronidases (SVHYs) induce local tissue destruction[6,7,8]; their neutralization by natural and synthetic compounds has failed to reach the clinic[9,10,11] This is not due to lack of neutralizing potency of the antivenoms or ineptness of the inhibitors, but rather to the rapid development of local pathology with an unknown cause, which prevents the therapeutic antibodies/inhibitors from accessing the damaged site[1]. We demonstrate that E. carinatus venom causes formation of NETs, resulting in the accumulation of venom toxins at the injection site and leading to continued tissue degradation. We show that NETs could be degraded by externally added DNase 1, which could be a possible treatment for this type of snakebite
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