, 2000), we conducted experiments in order to verify the effect o

, 2000), we conducted experiments in order to verify the effect of

BbV on hydrogen peroxide production. After 90 min of incubation the venom significantly stimulated human neutrophils to produce hydrogen peroxide compared to the negative control; however, there was no difference when compared with PMA (a positive control). BbV induced a significant release of hydrogen peroxide indicating that the BbV is able to stimulate neutrophils to activate the respiratory burst. In addition to our data, the literature shows that Bothrops alternatus venom induced the release of superoxide anion, another selleckchem reactive oxygen intermediate, by mice thioglycollate-elicited macrophages ( Setubal et al., 2011). Yet, the literature indicates that the injection of B. asper PFT�� and Bothrops jararaca venoms in the peritoneal cavity of mice induced the production of hydrogen peroxide by peritoneal leukocytes meaning they are capable of priming leukocytes for the respiratory burst ( Souza et al., 2012; Zamunér et al., 2001). In addition to the well-known capacity of neutrophils to phagocytose and kill invading microorganisms intracellularly, they can also capture and kill pathogens extracellularly through

the release of neutrophil extracellular traps (NETs). In order to understand the effect of BbV on neutrophil function, NETs liberation was assessed. Our results showed that BbV induced the liberation of NETs. However, there is no data in the literature so far showing the effect of Bothrops venom on NETs liberation which is the first description. Taking this into account and to complement PLEKHM2 other studies we designed an experiment to investigate the ability of BbV to induce IL-8 release. Results showed that BbV induced the release of this chemokine. Since BbV induces IL-8 release as well as ROS production and the literature shows that cytokines and ROS induce NETs liberation (Fuchs et al., 2007 and von Köckritz-Blickwede and Nizet, 2009), we suggest that IL-8 and ROS may contribute to NETs liberation induced by BbV. To

confirm our understanding of the effect of BbV on neutrophil function we decided to perform an experiment investigating the ability of BbV to induce IL-6 release. The results obtained indicate that BbV induced the release of this cytokine. Like IL-8 there is no data in the literature showing the effect of BbV on the production of IL-6 by isolated human neutrophils. Since BbV induces ROS production, we suggest that ROS may contribute to IL-6 release induced by BbV. Accordingly, the literature shows that intramuscular injection of B. asper venom induced an increase in IL-1beta and IL-6 in the muscle ( Chaves et al., 2005). In addition, levels of proinflammatory cytokines IL-6 and TNF-α were significantly increased after B. asper venom injection ( Zamunér et al., 2005).

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