title: Mucosal mast cell proteases are involved in colonic permeability alterations and subsequent bacterial translocation in endotoxemic rats.
abstract: 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.
authors.affiliation: 4MR 1054, INRA, Neuro-Gastroenterology and Nutrition Unit, ESA-Purpan, Toulouse, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Moriez
authors.forename: Mathilde
authors.initials: M
authors.lastname: Leveque
authors.forename: Christel
authors.initials: C
authors.lastname: Salvador-Cartier
authors.forename: Frederic
authors.initials: F
authors.lastname: Barreau
authors.forename: Vassilia
authors.initials: V
authors.lastname: Theodorou
authors.forename: Jean
authors.initials: J
authors.lastname: Fioramonti
authors.forename: Lionel
authors.initials: L
authors.lastname: Bueno
authors.forename: Helene
authors.initials: H
authors.lastname: Eutamene
mesh_terms: D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D053818:Chymases / Q000378:metabolism; D003106:Colon / Q000382:microbiology / Q000503:physiopathology; D019446:Endotoxemia / Q000382:microbiology* / Q000503:physiopathology*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000382:microbiology / Q000503:physiopathology; D007832:Lasalocid / Q000031:analogs & derivatives / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008070:Lipopolysaccharides; C440499:lipopolysaccharide, Escherichia coli O111 B4; C083294:chymase 2; D053818:Chymases; C029086:bromolasalocid; D007832:Lasalocid