Menaldo Danilo L, Bernardes Carolina P, Zoccal Karina F, Jacob-Ferreira Anna L, Costa Tássia R, Del Lama Maria P F M, Naal Rose M Z G, Frantz Fabiani G, Faccioli Lúcia H, Sampaio Suely V
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Mol Immunol. 2017 May;85:238-247. doi: 10.1016/j.molimm.2017.03.008. Epub 2017 Mar 16.
Bothrops envenomations can promote severe inflammatory responses by inducing edema, pain, leukocyte recruitment and release of chemical mediators by local cells. In the present study, two toxins from Bothrops atrox venom (the P-I metalloprotease Batroxase and the acidic phospholipase A BatroxPLA) were evaluated in relation to their inflammatory effects induced in vivo and in vitro, mainly focusing on the participation of different immune cells and inflammatory mediators. Both toxins mainly promoted acute inflammatory responses with significant recruitment of neutrophils in the early hours (1-4h) after administration into the peritoneal cavity of C57BL/6 mice, and increased infiltration of mononuclear cells especially after 24h. Among the mediators induced by both toxins are IL-6, IL-10 and PGE, with Batroxase also inducing the release of L-1β, and BatroxPLA of LTB and CysLTs. These responses pointed to possible involvement of immune cells such as macrophages and mast cells, which were then evaluated in vitro. Mice peritoneal macrophages stimulated with Batroxase produced significant levels of IL-6, IL-1β, PGE and LTB, whereas stimulus with BatroxPLA induced increases of IL-6, PGE and LTB. Furthermore, both toxins were able to stimulate degranulation of RBL-2H3 mast cells, but with distinct concentration-dependent effects. Altogether, these results indicated that Batroxase and BatroxPLA promoted local and acute inflammatory responses related to macrophages and mast cells and to the production of several mediators. Our findings should contribute for better understanding the different mechanisms of toxicity induced by P-I metalloproteases and phospholipases A after snakebite envenomations.
J Venom Anim Toxins Incl Trop Dis. 2015-8-13
Curr Drug Targets. 2025
Toxins (Basel). 2024-12-2
Toxins (Basel). 2023-3-4
Mediators Inflamm. 2022