Investigation of the role of desensitization on Natterin antagonism

Abstract

Studies developed previously by our group show that the venom of Thalassophryne nattereri venomous fish develops an inappropriate cellular inflammatory response characterized by a reduced number of leukocytes at the site of injury. As from a combined proteomic and transcriptomic approaches the composition of T. nattereri venom was studied and the majority proteins present in the venom of this fish have been identified. Natterins, as they were named, are able to induce edema and nociception and presents protease action because it cleave the human kininogen and synthetic peptides derived from kininogen releasing Lys-BK and kallidin. Recently we demonstrated that Natterins are responsible for the inhibition of leukocyte recruitment observed in the poisoning, exactly because they reduce the rolling and migration of leukocytes in the inflammation induced by LPS and by chemokine KC. This inhibition is dependent of the signaling pathway TLR/MyD88/PI3K and features the participation of protein family serine/threonine phosphatases, contributing significantly to the survival of animals induced to endotoxic shock by LPS. Therefore, in this study we sought to understand how the Natterinas act to inhibit the rolling and migration of leukocyte. The elucidation of the action mechanisms of majority toxins (Natterins) present in the venom will enable the understanding of the deficient inflammatory process observed in the poisoning, suggesting therapeutic interventions more efficient.