Immune cells and mediators involved in the inflammatory responses induced by a P-I metalloprotease and a phospholipase A2from Bothrops atrox venom.
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 A2BatroxPLA2) 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 PGE2, with Batroxase also inducing the release of L-1β, and BatroxPLA2of LTB4and 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, PGE2and LTB4, whereas stimulus with BatroxPLA2induced increases of IL-6, PGE2and 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 BatroxPLA2promoted 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 A2after snakebite envenomations.
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: danmenaldo@yahoo.com.br.
Danilo L
DL
Menaldo
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Carolina P
CP
Bernardes
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Karina F
KF
Zoccal
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Anna L
AL
Jacob-Ferreira
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Tássia R
TR
Costa
Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil; Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Universidade Estadual de Campinas, Campinas, SP, Brazil.
Maria P F M
MP
Del Lama
Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil; Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Universidade Estadual de Campinas, Campinas, SP, Brazil.
Rose M Z G
RM
Naal
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Fabiani G
FG
Frantz
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Lúcia H
LH
Faccioli
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: suvilela@usp.br.
Suely V
SV
Sampaio
D000818:Animals; D017837:Bothrops; D003435:Crotalid Venoms / Q000633:toxicity*; D004195:Disease Models, Animal; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology*; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D045726:Metalloproteases / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D054467:Phospholipases A2 / Q000633:toxicity
C000608699:Batroxase, Bothrops atrox; D003435:Crotalid Venoms; D018836:Inflammation Mediators; D054467:Phospholipases A2; D045726:Metalloproteases
Bothrops atrox; Inflammation; Mediators; Metalloprotease; Phospholipase A(2); Snake venoms