Immune cells and mediators involved in the inflammatory responses induced by a P-I metalloprotease and a phospholipase A(2) from Bothrops atrox venom

Author(s)

Menaldo, Danilo L. ; Bernardes, Carolina P. ; Zoccal, Karina F. ; Jacob-Ferreira, Anna L. ; Costa, Tassia R. ; Del Lama, Maria P. F. M. ; Naal, Rose M. Z. G. ; Frantz, Fabiani G. ; Faccioli, Lucia H. ; Sampaio, Suely V.

• Document type: Journal article
• Source: Molecular Immunology; v. 85, p. 238-247, MAY 2017.
• Web of Science Citations: 7

Abstract

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(2) BatroxPLA(2)) 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 24 h. Among the mediators induced by both toxins are IL-6, IL-10 and PGE(2), with Batroxase also inducing the release of L-1 beta, and BatroxPLA2 of LTB4 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-1 beta, PGE(2) and LTB4, whereas stimulus with BatroxPLA(2) induced increases of IL-6,PGE2 and LTB4. 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(2) 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(2) after snakebite envenomations. (C) 2017 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis
• Grantee: Suely Vilela
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 12/11963-1 - Effects of a metalloprotease and an acidic Phospholipase A2 from Bothrops atrox snake venom on the complement system and the inflammatory process
• Grantee: Danilo Luccas Menaldo
• Support type: Scholarships in Brazil - Post-Doctorate