Effect of colonic inflammation on mucin inhibition of Escherichia coli RDEC-1 binding in vitro.
Intestinal mucus protects the underlying epithelium against adhesion and invasion by microbial pathogens and their products. In inflamed colonic mucosa there are both histochemical and biochemical changes in the major organic constituent of mucus, goblet cell-derived mucin. To determine if these changes result in differences in functional properties of mucin, inhibition of adherence of piliated Escherichia coli, strain RDEC-1 (serotype O15:H-), by mucin purified from distal colons of normal rabbits was compared with inhibition by mucin from colons of rabbits with dinitrochlorobenzene-induced colitis. Histology from inflamed colons revealed evidence of chronicity with a chronic inflammatory cell infiltrate, depletion of mucous glands, and branching of crypts. Mucin was purified from crude mucus of distal colonic mucosa by sequential ultracentrifugation and characterized by gel electrophoresis and amino acid analysis. The rabbit enteropathogen RDEC-1 was grown to promote expression of adherence pili. A nonpiliated mutant, strain M34, was used as a negative control. A concentration-dependent inhibition of piliated RDEC-1 binding was shown using mucins derived from both inflamed and noninflamed colons. However, equivalent dry weights of mucin purified from inflamed colons showed less inhibition of bacterial binding (10.3% inhibition +/- 5.2%; mean +/- SD) compared with mucin from normal colons (47.6% +/- 10.8%; P less than 0.05). Mucin purified from additional animals with hapten-induced colitis but treated with the oral leukotriene B4-receptor antagonist SC-41930 showed intermediate inhibition of RDEC-1 binding (35.6% +/- 14.3%). It is concluded that mucin derived from inflamed distal colon of rabbits failed to inhibit in vitro binding of piliated RDEC-1, and by decreasing mucosal inflammation, this functional alteration of mucin was partially reversed.
Mack
D R
DR
Department of Pediatrics, Hospital for Sick Children, University of Toronto, Ontario, Canada.
Gaginella
T S
TS
Sherman
P M
PM
D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects; D003092:Colitis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000737:chemistry / Q000502:physiology; D004137:Dinitrochlorobenzene; D004926:Escherichia coli / Q000472:pathogenicity; D006168:Guinea Pigs; D007975:Leukotriene B4 / Q000502:physiology; D008297:Male; D009077:Mucins / Q000502:physiology*; D011817:Rabbits
D004137:Dinitrochlorobenzene; D009077:Mucins; D007975:Leukotriene B4