Vatairea guianensis lectin stimulates changes in gene expression and release of TNF-α from rat peritoneal macrophages via glycoconjugate binding

J Mol Recognit. 2021 Oct;34(10):e2922. doi: 10.1002/jmr.2922. Epub 2021 Jun 16.

Abstract

Using a rat model of peritonitis, we herein report the inflammatory effect induced by the lectin isolated from Vatairea guianensis (VGL) seeds in the context of interactions between VGL and both toll-like receptor 4 (TLR4) and tumor necrosis factor receptor 1 (TNFR1). Peritoneal macrophages were stimulated with VGL for dose-dependent gene expression and release of TNF-α. In vivo results showed that VGL (1 mg/kg; intraperitoneal) induced peritonitis in female Wistar rats. Leukocyte migration, macrophage activation, and protein leakage were measured 3 and 6 hours after induction. In vitro, peritoneal macrophages were stimulated with VGL for gene expression and TNF-α dosage (mean ± SEM (n = 6), analysis of variance, and Bonferroni's test (P < .05)). In silico, VGL structure was applied in molecular docking with representative glycans. It was found that (a) VGL increases vascular permeability and stimulates leukocyte migration, both rolling and adhesion; (b) lectin-induced neutrophil migration occurs via macrophage stimulation, both in vitro and in vivo; (c) lectin interacts with TLR4 and TNFR1; and (d) stimulates TNF-α gene expression (RT-PCR) and release from peritoneal macrophages. Thus, upon lectin-glycan binding on the cell surface, our results suggest that VGL induces an acute inflammatory response, in turn activating the release of peritoneal macrophages via TNF-α and TLR and/or TNFR receptor pathways.

Keywords: Vatairea guianensis; glycoconjugates; inflammation; lectins; macrophage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Fabaceae / chemistry*
  • Female
  • Gene Expression Regulation / drug effects
  • Glycoconjugates / chemistry
  • Glycoconjugates / metabolism*
  • Leukocytes / drug effects
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / metabolism
  • Peritonitis / chemically induced
  • Peritonitis / metabolism
  • Peritonitis / pathology
  • Plant Lectins / chemistry
  • Plant Lectins / metabolism
  • Plant Lectins / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Tumor Necrosis Factor, Type I / chemistry
  • Receptors, Tumor Necrosis Factor, Type I / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Glycoconjugates
  • Plant Lectins
  • Receptors, Tumor Necrosis Factor, Type I
  • Tlr4 protein, rat
  • Tnfrsf1a protein, rat
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha