EFFECT OF TOXINS ISOLATED FROM BOTHROPS VENOMS ON CELLULAR MIGRATION PROFILE AND MACROPHAGES ACTIVATION OF WILD-TYPE AND CASPASE 1-DEFICIENT MICE
Ranéia PA1, Clissa PB1, Bortoluci KR2, Faquim-Mauro EL1
1 Laboratório de Imunopatologia, Instituto Butantan, Brasil; 2 Disciplina de Microbiologia, Universidade Federal de São Paulo, Brasil
Introduction: Jararhagin (JAR) and bothropstoxin-I (BthTX-I) toxins, from Bothrops jararaca and Bothrops jararacussu, respectively are involved in the inflammation and tissue injury observed in the envenomations by these snakes. The resolution of tissue damage involves the interaction between the tissue repair mechanisms and the immune system. The inflammatory response is initiated by the recognition of pathogen-associated molecular patterns (PAMPs) or endogenous danger signals (DAMPs) by several Pattern Recognition Receptors (PRRs), including inflammasomes. Inflammasomes are cytosolic multiprotein complexes responsible for caspase-1 activation with subsequent release of IL-1β and induction of cell death. Objectives: Study the participation of inflammasome in response to the toxins isolated from Bothrops venoms. Methods: In in vivo experiments, C57BL/6 (WT) and Caspase-1-/- (Casp1-/-) mice received JAR or BthTX-I (50µg/animal) in the gastrocnemius muscle and after 4, 24 and 72h to the analysis of cellular migration. In in vitro It was also assessed the ability of the JAR and BthTX-I to induce IL-1β and IL-6 secretion as well as LDH release by macrophages differentiated from bone marrow cells (BMDM) of C57BL/6 and Casp 1-/- mice Results and Discussion: The results showed difference in neutrophils and macrophages migration between the groups of WT mice injected with JAR or BthTX-I and Casp1-/- mice injected with the toxins. We observed that BthTX-I induced higher levels of IL-1β and IL-6 secretion by BMDM from WT mice when compared with JAR. Both toxins induced LDH release in cultures of BMDM from WT mice. Furthermore, the IL1β secretion and LDH release were dependent of caspase-1, since this cytokine was not detected and the LDH liberation was lower in cultures of BMDM from Casp1-/- incubated with the toxins. Our previous results suggest that both snake toxins induce inflammasomes activation, suggesting the involvement of these platforms in the inflammation and tissue injury observed in the envenomations by them.
|4 - IMMUNOLOGY AND VACCINES||21th Annual Scientific Meeting of Instituto Butantan.|