Universidad de Murcia. Departamento de Biología Celular e Histología
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 enzymelinked 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 celldeficient 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 selfrenewal 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