A murine model of ulcerative colitis: induced with sinusitis-derived superantigen and food allergen.
BACKGROUND
The etiology of ulcerative colitis (UC) is to be understood. The basic pathological feature of UC is intestinal chronic inflammation. Superantigen, such as Staphylococcus enterotoxin B (SEB), is reported to compromise intestinal barrier function by increasing epithelial permeability and initiate inflammation in the intestinal mucosa. Inasmuch as anatomic position of the sinus, chronic sinusitis-derived SEB may follow the secretion and to be swallowed down to the gastrointestinal tract and induce lesions to the intestinal mucosa.


METHODS
Sinus wash fluid (SWF, containing SEB) was collected from a group of patients with both chronic sinusitis (CS) and UC. A group of mice were sensitized to ovalbumin (OVA) in the presence of SWF. The sensitized mice were challenged with the specific antigen OVA. The inflammatory status of the colonic tissue was determined with histology, serology and electron microscopy. Using horseradish peroxidase (HRP) as a tracer, another group of mice was stimulated with SWF for 2 hours. The HRP activity was detected in the colonic tissue with enzymatic approaches and electron microscopy.


RESULTS
Epithelial hyperpermeability in colonic epithelium was induced by stimulating with SWF. The HRP activity in the colonic mucosa was almost 11 times more in the SWF treated group (3.2 +/- 0.6 microg/g tissue) than the control group (0.3 +/- 0.1 microg/g tissue). Mice were sensitized using a mixture of SWF and OVA (serum OVA-specific IgE was detected with a highest titer as 1:64). Challenge with OVA induced extensive inflammation in the colonic mucosa by showing (1) marked degranulation in mast cells (MC, 46.3 +/- 4.5%) and eosinophils (Eo, 55.7 +/- 4.2%); (2) inflammatory cell infiltration (MC = 145.2 +/- 11.4; Eo = 215.8 +/- 12.5; mononuclear cell = 258.4 +/- 15.3/mm2 tissue); (3) increased MPO activity (12.9 +/- 3.2 U/g tissue) and inflammatory scores (1.8 +/- 0.3); (4) mucosal surface ulcers; (5) edema in the lamina propria; (6) bacterial translocation and abscess formation in the subepithelial region.


CONCLUSIONS
Introducing Sinusitis-derived SEB-containing SWF to the gastrointestinal tract compromised colonic mucosal barrier function increasing epithelial permeability to luminal macromolecular protein in mice. The SWF facilitated colonic mucosal sensitization to luminal antigen. Multiple challenging the sensitized colonic mucosa with specific antigen OVA induced inflammation, induced a condition similar to human ulcerative colitis.
Yang
Ping-Chang
PC
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. yangp@mcmaster.ca
Wang
Chang-Sheng
CS
An
Zi-Yuan
ZY
D000328:Adult; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000276:immunology*; D003106:Colon / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003967:Diarrhea / Q000276:immunology; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000276:immunology*; D004804:Eosinophils / Q000473:pathology; D005260:Female; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D008875:Middle Aged; D010047:Ovalbumin / Q000276:immunology*; D010256:Paranasal Sinuses / Q000378:metabolism; D010539:Permeability; D012852:Sinusitis / Q000276:immunology* / Q000378:metabolism; D018089:Superantigens / Q000276:immunology*; D007507:Therapeutic Irrigation
D000942:Antigens, Bacterial; D004768:Enterotoxins; D018089:Superantigens; D007073:Immunoglobulin E; C031818:enterotoxin B, staphylococcal; D010047:Ovalbumin; D006735:Horseradish Peroxidase
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