Gene Expression Profile of Neutrophil Extracellular Traps (NETs) Stimulated by L-Amino Acid Oxidase from <i>Calloselasma rhodostoma</i> Venom

Abstract

The focus of this study is to investigate the gene expression related to the formation of neutrophil extracellular traps (NETs) stimulated by Calloselasma rhodostoma L-amino acid oxidase (Cr-LAAO). LAAOs found in snake venom have been shown to activate human neutrophils, leading to the production of reactive oxygen species (ROS), chemotaxis, phagocytosis, and the release of pro-inflammatory cytokines and lipid mediators. Additionally, it has been found that Cr-LAAO activates NADPH oxidase, which is responsible for the release of ROS. Neutrophils are known to release NETs to combat pathogens, and this process involves the migration of DNA from the nucleus to the cytoplasm, where it merges with the contents of the granules to produce NETs. Initially, the formation of NETs was associated with cell death, and this process was known as NETosis. However, two forms of NETosis have now been identified: classical or suicidal NETosis, which results in cell death, and vital NETosis, in which the cell retains its viability and many of its effector functions. To evaluate the gene expression related to the formation of NETs, a microarray assay was performed on human neutrophils stimulated with Cr-LAAO. The results show that Cr-LAAO stimulates the expression of important genes for the formation of NETs, such as TXNIP, FOXO3, PPARA, ELANE, CXCL8, and PADI4. This is the first report that shows the transcriptome of neutrophils related to Cr-LAAO-stimulated NETosis, which may lead to the development of local inflammatory effects observed in snakebite victims.

Keywords

• neutrophil
• snake venom
• NETs
• inflammation