Analysis of immediate ex vivo release of nitric oxide from human colonic mucosa in gastrointestinally mediated allergy, inflammatory bowel disease and controls.
Nitric oxide (NO) is a local mediator in inflammation and allergy. The aim of this study was to investigate whether live incubated colorectal mucosal tissue shows a direct NO response ex vivo to nonspecific and specific immunological stimuli and whether there are disease-specific differences between allergic and chronic inflammatory bowel disease (IBD). We took biopsies (n=188) from 17 patients with confirmed gastrointestinally mediated food allergy, six patients with inflammatory bowel disease, and six control patients. To detect NO we employed an NO probe (WPI GmbH, Berlin, Germany) that upon stimulation with nonspecific toxins (ethanol, acetic acid, lipopolysaccharides), histamine (10(-8)-10(-4)M), and immune-specific stimuli (anti-IgE, anti-IgG, known food allergens) directly determined NO production during mucosal oxygenation. Non-immune stimulation of the colorectal mucosa with calcium ionophore (A23187), acetic acid, and ethanol induced a significant NO release in all groups and all biopsies. Whereas, immune-specific stimulation with allergens or anti-human IgE or -IgG antibodies did not produce significant release of NO in controls or IBD. Incubation with anti-human IgE antibodies or allergens produced a ninefold increase in histamine release in gastrointestinally mediated allergy (p<0.001), but anti-human IgE antibodies induced NO release in only 18% of the allergy patients. Histamine release in response to allergens or anti-human IgE antibodies did not correlate with NO release (r(2)=0.11, p=0.28). These data show that nonspecific calcium-dependent and toxic mechanisms induce NO release in response to a nonspecific inflammatory signal. In contrast, mechanisms underlying immune-specific stimuli do not induce NO production immediately.
Funct. Tissue Diagnostics, Department of Medicine I, University Erlangen, Erlangen, Germany. Martin.Raithel@uk-erlangen.de
M
M
Raithel
A F
AF
Hagel
Y
Y
Zopf
P B
PB
Bijlsma
T M
TM
de Rossi
S
S
Gabriel
M
M
Weidenhiller
J
J
Kressel
E G
EG
Hahn
P C
PC
Konturek
D000485:Allergens / Q000276:immunology; D016022:Case-Control Studies; D003106:Colon / Q000276:immunology*; D005512:Food Hypersensitivity / Q000276:immunology*; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology; D009569:Nitric Oxide / Q000276:immunology*
D000485:Allergens; D009569:Nitric Oxide; D007073:Immunoglobulin E