Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010346 (Crohn's disease)
 21,615 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Circulating neutrophils were investigated in 15 patients with Crohn's disease (CD), 15 with ulcerative colitis (UC), and 15 healthy volunteers. Dose-response curves for chemotaxis in Boyden chambers were analysed for sensitivity to leukotriene B4 (LTB4), its 20-hydroxy-LTB4 (20-OH-LTB4) and 20-carboxy-LTB4 (20-COOH-LTB4) catabolites, and 5- and 15-hydroxyeicosatetraenoic acids (HETEs). Positive controls included: complement 5a (C5a), formy-L-methionyl-L-leucyl-L-phenylalanine (f-Met-Leu-Phe), and casein. Control chemotaxis test were performed at concentrations yielding optimal responses in leucocytes of healthy volunteers. Chemotaxis to suboptimal concentrations of LTB4 1.0 and 3.2 nmol/l, and 5-HETE 316 nmol/l, was markedly depressed in patients with chronic inflammatory bowel disease (CIBD). Analyses of individual dose-response curves revealed an underlying decreased sensitivity to LTB4 in 11 out of 30 patients, to 5-HETE in 10 out of 30 patients with a corresponding decrease of median sensitivity to LTB4 and 5-HETE in both CD and UC. Peak responses to LTB4, 5-HETE, f-Met-Leu-Phe, and casein were identical in the three groups tested, whereas the C5a values were significantly depressed in both groups of patients (p less than 0.05). The potency of LTB4 exceeded that of 5-HETE by a factor of approximately 100 whereas 20-OH-LTB4 was nearly as potent as LTB4. 20-COOH-LTB4 and 15-HETE did not activate chemotaxis of human neutrophils. These findings are suggestive of a competitive inhibition of receptors with heterogeneity for LTB4 and 5-HETE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of neutrophil chemotaxis by leukotriene B4 and 5-hydroxyeicosatetraenoic acid in chronic inflammatory bowel disease. 282 70

The metabolism of endogenous arachidonic acid P(AA) was investigated in activated neutrophils from 20 patients with Crohn's disease, 20 with ulcerative colitis, and 25 healthy volunteers. 1-14C-P(AA) was incorporated into intracellular pools of phospholipids prior to activation of the cells with ionophore A23187 and analyses of released arachidonic acid metabolites by thin layer chromatography. Total release of radioactivity expressing the release of arachidonic acid and its metabolites, was equal in the experimental and control groups, which suggests a normal substrate availability. In contrast, there was a marked increase in the relative release of leucotriene B4 (LTB4) and its omega-oxidation products, 20-hydroxy-LTB4 (20-OH-LTB4) and 20-carboxy-LTB4 (20-COOH-LTB4), with LTB4 values exceeding the reference interval in seven of 20 patients with Crohn's disease, median 8.7%, and in six of 20 patients with ulcerative colitis, median 7.7%, as compared with a median of 5.3% in healthy volunteers. Furthermore, a decreased release of unmetabolised arachidonic acid, correlating inversely with the release of LTB4 in all experimental and control groups, and normal values for the production of other metabolites of arachidonic acid--for example, 5-hydroxyeicosatetraenoic acid (5-HETE) and 12-hydroxyheptadecatrienoic acid (HHT), point to an enzymatic abnormality such as increased activity of leucotriene B synthetase. An increased capacity for release of LTB4, the major pro-inflammatory metabolite of arachidonic acid lipoxygenation by polymorphonuclear leucocytes, may contribute to perpetuation of the inflammation and to tissue destruction in chronic inflammatory bowel disease. Our findings agree with previous reports of an increased release of LTB4 by the colonic mucosa in this condition.
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PMID:Abnormal metabolism of arachidonic acid in chronic inflammatory bowel disease: enhanced release of leucotriene B4 from activated neutrophils. 303 Sep 3