Aspectos estruturais do reconhecimento de carboidratos por uma lectina manose-específica de sementes de Dolichos lablab com atividade pró-inflamatória e hipernociceptiva

Abstract

Lectins are proteins that specifically bind to carbohydrates and form complexes with molecules and biological structures containing saccharides, without altering the covalent structure of the glycosyl ligands, these proteins have great biotechnological potential because of its diverse biological activities. The aim of this study was to investigate the effects of Dolichos lablab lectin in inflamatory process and analyze its interaction with carbohydrates. The Man/Glc-specific lectin of Dolichos lablab, termed FRIL, is a dimeric two-chain (αβ)2 lectin presenting 67 kDa molecular mass. The interaction of FRIL with carbohydrates, as determined by molecular docking, showed that this lectin has highest affinity to the carbohydrate trimannoside (-135.618 MDS), followed by trehalosamine (-127.072 MDS) and αα-trehalose (-121.729 MDS). FRIL evoked dose-dependent paw edema, increasing animal paw volumes. The edematogenic effect of FRIL was paralleled by a significant increase in vascular permeability, about 10-fold higher compared to control. FRIL also significantly raised the animals flinch reaction in the first, third and fifth hours in response to mechanical stimulation. Injection of α-methyl-D-mannoside associated with FRIL inhibited either edema, at the third hour and hypernociception. The histopathological analysis of animal paws showed a characteristically acute inflammatory process that included severe infiltration of mixed leukocytes, changes in cytoarchitecture, edema and focal areas of hemorrhage. In addition, in silico assays confirmed that FRIL preferentially interacts with trimannoside that makes up the core N-glycans cell. Therefore, our study supports the hypothesis that the lectin domain and/or the likely glycoconjugates containing α-methyl-D-mannoside and trimannosides residues contribute to the inflammatory effects of FRIL.