Lipopolysaccharide induces the early enhancement of mice colonic mucosal paracellular permeability mainly mediated by mast cells

Histol Histopathol. 2019 Feb;34(2):191-200. doi: 10.14670/HH-18-039. Epub 2018 Sep 13.

Abstract

The alteration of intestinal mucosal barrier is considered to be the central pathophysiological process in response to gastrointestinal infections, and mucosal microstructural damage is a major factor for enhancing epithelial permeability in persistent bacterial infections. However, the mechanism involved in hyperpermeability in the early stage of acute bacterial infections is not fully understood. In the present study, fluorescein isothiocyanate-dextran across and transepithelial resistance measured in Ussing chambers were used to assess the intestinal paracellular permeability. Mast cell activation was evaluated by western blotting for the presence of tryptase released from mast cells. Serum levels of interleukin-6 were evaluated using enzyme-linked immunosorbent assay. Our results indicated that mast cells played a pivotal role in colonic mucosal hyperpermeability in wild type mice treated with lipopolysaccharide (LPS) for 2 h. And the effect of LPS was mainly dependent on mast cell degranulation, while no change in permeability was observed in the mast cell-deficient mice (Wads⁻/⁻) after LPS administration. No obvious changes of the mucosal structure including histomorphological architecture and expression of intercellular junction proteins were obtained in either wild type or Wads⁻/⁻ mice after LPS stimulation by hematoxylin and eosin staining, immunofluorescence staining and western blot analysis. Furthermore, the self-renewal of intestinal epithelia, detected by using proliferation marker 5'-bromo-2'-deoxyuridine, was not involved in increased permeability. Collectively, activation of mast cells induced by LPS mediated intestinal hyperpermeability in the initial stage, and played a crucial role in barrier dysfunction rather than mucosal microstructural damage in acute enterogenous bacterial infection.

MeSH terms

  • Animals
  • Bacterial Infections / immunology
  • Bacterial Infections / metabolism
  • Cell Degranulation / drug effects
  • Cell Degranulation / immunology
  • Colon
  • Disease Models, Animal
  • Intercellular Junctions / drug effects*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism*
  • Lipopolysaccharides / toxicity*
  • Mast Cells / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Permeability

Substances

  • Lipopolysaccharides