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

Swethakumar, B and NaveenKumar, SK and Girish, KS and Kemparaju, K (2020) The action of Echis carinatus and Naja naja venoms on human neutrophils; an emphasis on NETosis. In: Biochimica et Biophysica Acta - General Subjects, 1864 (6).

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Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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. Significance: 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.

Item Type:	Journal Article
Publication:	Biochimica et Biophysica Acta - General Subjects
Publisher:	ELSEVIER
Additional Information:	The copyright of this article belongs to ELSEVIER
Department/Centre:	Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	24 Jun 2020 06:36
Last Modified:	24 Jun 2020 06:36
URI:	http://eprints.iisc.ac.in/id/eprint/64758

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