The action of Echis carinatus and Naja naja venoms on human neutrophils; an emphasis on NETosis

• Published in: Biochimica et biophysica acta. General subjects Vol. 1864; no. 6; p. 129561
• Main Authors: Swethakumar, Basavarajaiah, NaveenKumar, Somanathapura K., Girish, Kesturu S., Kemparaju, Kempaiah
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2020
• Subjects: calcium; Calcium ions; cell communication; cell viability; chromatin; cobra venoms; deoxyribonucleases; Echis carinatus; humans; innate immunity; mitochondrial DNA; mitogen-activated protein kinase; Naja naja; neutrophils; nuclear genome; pathophysiology; pharmacodynamics; protein kinase C; Reactive oxygen species; snake bites; snakes; Suicidal NETosis; toxicity; Vital NETosis; Reactive oxygen species; Suicidal NETosis; Echis carinatus; Naja naja; Vital NETosis; Calcium ions
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2020.129561

Neutrophils are the first line defense cells of the innate immunity. As a final defense, they discharge their de-condensed chromatin/DNA fibers, the NETs (Neutrophil Extracellular Traps), by a process called NETosis. Two types of NETosis have been currently described: the suicidal/delayed/classical-type, which is ROS dependent that results in the ejection of nuclear DNA, and the vital/rapid/early-type, which may or may not require ROS but, eject nuclear/mitochondrial DNA or both. Thus, Echis carinatus and Naja naja venoms are comparatively studied for their NET inducing property. Formation of NETs, cell viability, ROS, and Ca2+ levels are estimated. An in vivo toxicity study and possible cellular signaling have been addressed using immunoblots and pharmacological inhibitors. E. carinatus and N. naja venoms respectively induce suicidal and vital NETosis. E. carinatus venom induces NETosis by activating NOX and PAD-4 enzymes in a ROS dependent manner via PKC/ERK/JNK signaling axis, while N. naja venom does it by activating PAD-4 enzyme, but independent of ROS requirement and as well as PKC/ERK/JNK activation. For the first time our study demonstrates the distinct action of E. carinatus and N. naja venoms on the process of NETosis. NETosis being a newly explored area in snake venom pharmacodynamics, it is important to study its impact on the various pathophysiological properties induced by snake venoms. Understanding the varied actions of snake venoms on neutrophils/blood cells and the role of DNase are likely to provide insights for better management of snakebite pathophysiology. •E. carinatus venom induces NETosis by activating NOX and PAD4 via PKC/ERK/JNK signaling axis in a ROS dependent manner.•N. naja venom does it by activating PAD4, but independent of ROS and PKC/ERK/JNK signaling axis.•This study is first to demonstrate the distinct types of NETosis induced by E. carinatus and N. naja venoms.•This study is likely to provide new insights for the better management of snakebite pathophysiology.•Differential action of snake venoms may also offer scope for a better understanding of the complex mechanism of NETosis.