Overexpression of macrophage migratory inhibitory factor (MIF) in human inflammatory bowel disease (IBD)

2669

CD. Theseenzymesare involved in the production of the secretor and Lewis antigens respectively. These data suggest that changes in the abundance of fucosyltransferases may be important in the alteration in glycosylation seen in inflammatory bowel disease.

Decreased Phosphatidylcholineand Lysophosphatidylcholinein Intestinal Mucus of Patients with Ulcerative Colitis: A Possible Clue to Pathogenesis? Robert Ehehalt, Univ of Heidelberg, HeidelbergGermany; Wolf-Dieter Lehmann, Gerhard Erben, German Cancer Research Ctr, HeidelbergGermany; Woifgang Stremmel, Univ of Heidelberg, HeidelbergGermany

Mean(SEM)abundanceof FUT 1,2 5 and 6 expressedas a percenlageof normalcolon expression

Background:A defectivemucus composition representsa key pathogeneticfactor for intestinal injury. Phosphatidylcholine (PC) is an essential component contributing to formation of a hydrophobic mucous layer. For evaluation of phosphatidylcholine in the pathogenesis of ulcerative colitis, the concentration and composition of PC in the rectal mucus of patients with inactive ulcerativecolitis was determined. Electrosprayionization (ESI) tandem spectroscopy (MS/MS) allows quantification of phosphatidylcholinespecies and enables us first time to analyzecrude extracts on a pmol level. Methods: Phosphatidylcholineand lysophosphatidylcholine (LPC) species from rectoscopicallyacquired mucus aliquots of patients with inactive ulcerative colitis were analyzedby nano-ESI MS/MS and quantified with internal standardization. For evaluation of the origin of intestinal PC we used a mice model with absent biliary phospholipid secretion (mdr2 (-/-)mice). In comparison to normal controls (mdr2 ( + / + ) mice), mucus PC composition was determined in different segments of the gut. Results: Patients with inactive ulcerative colitis showed significant less PC and LPC in rectal mucus (1105 _+ 813 pmol/mg dry weight) comparedto control subjects (307 -+ 414 pmol/mg dry weight). The quality of PC and LPC species was not significant different in both groups. We found in about 90 % unsaturated PC species (PC 16:0/18:1; PC 16:0/18:2; PC 18:0/18:1; PC 18:0/18:2; LPC 16:0; LPC 18:0). In mdr2 ( - / - ) mice and control animals no significant difference in PC composition was found, indicating that luminal PC is of intestinal and not biliary origin. Conclusion: Nano-ESI MS/MS is a suitable tool to analyzeand quantify small amounts of PC in human mucus. Patients with ulcerative colitis have significant less PC in their intestinal mucus despite a comparable PC species composition pattern. This indicates that impaired intestinal PC secretion is a characteristic feature in ulcerative colitis and may predisposeto an impaired mucosalbarrier function facilitating inflammatoryattacks by noxious colonic contents. The work was supported by a grant of the Dietmar Hopp Foundation.

2670 The Role of Corticotrophin-Releasing Factor (CRF), Serotonin (6-HT) and Cholecytokinin (CCK) in the Pathogenesisof Stress-induced Experimental Colitis Mehmet A. Gulpinar, Dilek Ozbeyli,Serap Arbak, 8errak C. Yegen, Marmara Univ, Istanbol Turkey BACKGROUND:Acute stress causes hyperactivationof CRF, CCKand 5-HT neurons, whereas chronic stress leadsto hypoactivation.Central nervous system (CNS) may modulate aspects of gastroinestinal inflammation through alterations (sensitization/desensitization)of the autonomic nervous system and/or hypothalamo-pituitary-adrenalaxis. The aim of the present study was to examine the impact of "acute stress" and "acute stress upon chronic stress" on the course of TNBS-inducedcolitis and to elucidatethe roles of central CRF, 001(8and 5HT3 receptors in this modulation. METHODS: In acute stress group, male Sprague-Dawley rats were placed in a plexiglass chamber and electric shock was applied (in the range of 0.30.6 mA for 5 s; 20 times/30 rain). In acute stress upon chronic stress group, following the electric shock on the 1't day, rats were put in the same chamber for 3 more days without giving shock and a "2-h restraint stress" was added on the 4~ day. In other groups, rats were injected intracerebroventricularly(icy; in 5 ~l) 10 rain before stress session with CRF receptor antagonist astressin (2.5/~g/rat), CCKBreceptor antagonist CI-989 (5 pg/rat) or 5HT3 receptor antagonist ramosetron (10 /~g/rat). Colitis was induced by the intracolonic administration of TNBS at the 4th hour after last exposure to stress and 3 days later the rats were decapitated. Damage in distal colon was assessed by tissue myeloperoxidase(MPO) activity, macroscopicand microscopic evaluation.RESULTS:While chronic stress or restraint stress alone had no significant effect, both the acute stress and acute stres upon chronic stressdecreased MPO activity (116-+10.49 and 96.65-+13.02 u/g; p<0.05-0.01), macroscopic (2.8-+0.53 and 2.25-+0.82) and microscopic (2.32-+0.1 and 1.9-+0.17) scores (p
Epitope fowesd FUT t RJT2 R/r5 FUT8

NC (n--'9)

H antigen Secmtor(So) Lewis*,SLex LewisX,SLe~

77 (5.0) 47(1.4)~ 168 (18.4) * 108 (6.7)

CD (n=5) 87 (20.4) 56(7.1)** 199(41.9)* 88 (23.4)

SiaJylLewisx (SLe~) * p
Relatives Familial CD Total

ASCA+ (%)

A-525

100 (8.9) 100(14.8) 100 (16.4) 100 (18.9)

UC (n=9)

101115 (8.7)

301141 (21.3)

2 CD paUents 19/89 (21.3)

3 CD patients 4/29 (13.8)

4 or more CD patients 7/23 (30.4)