LPS-induced
endotoxemia is associated with gut immune stimulation, mucosal
inflammation, colonic paracellular permeability (
CPP) alteration, and it promotes bacterial translocation (BT). Gut permeability increase linked to LPS promotes mucosal barrier dysfunction resulting to BT. However, the mechanisms involved in these alterations remain unknown. We aimed to evaluate the role of colonic mucosal mast cells and
luminal serine protease activity (PA) in the alterations of
CPP and BT induced by LPS. Rats receiving
doxantrazole, a
mast cell stabilizer, combined or not with LPS from Escherichia coli and
CPP as well as BT were evaluated after each treatment. Mucosal mast cell activation was assessed by histological methods and by rat
mast cell protease 2 level measurement in colonic content. Colonic
luminal PA and mucosal
inflammation (
myeloperoxidase activity) were biochemically determined. In addition, the ability of
luminal contents to act on
CPP was evaluated in vitro in Ussing chambers. Peripheral administration of LPS promoted mast cell degranulation and increased
CPP, BT, mucosal
myeloperoxidase activity as well as rat
mast cell protease 2 levels, and PA in colonic content. LPS-induced
CPP increase and BT were prevented by
doxantrazole. In vitro, exposure of the apical side of colonic tissues with supernatants from colonic contents of LPS-treated rats increased
CPP. This effect was blocked by the
serine protease inhibitor soybean
trypsin inhibitor. Our data bring evidence of a key role of mucosal mast cells in LPS-induced increase of
CPP and BT through the release of
serine proteases into the colonic lumen.