Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021390 (inflammatory bowel disease)
 23,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukocyte adhesion molecules are important in cell-cell interactions of the immune system. Lymphocyte function-associated antigen 1 (cluster designation 11a) mediates interactions between T cells and mononuclear phagocytes through its ligand, the intercellular adhesion molecule 1 (CD54), whereas complement receptors 3 (CD 11b) and 4 (CD11c) are involved in complement-mediated phagocytosis. Expression of CD11 molecules and intercellular adhesion molecule 1 was studied in colonic biopsy specimens from 20 patients with inflammatory bowel disease and 10 normal controls. In normal colon, few mononuclear phagocytes expressed lymphocyte function-associated antigen 1 and intercellular adhesion molecule 1 at high densities. The major adhesion molecule was CD11c. Thus, the largest population of normal colonic mononuclear phagocytes was represented by quiescent, resident macrophages with likely phagocytic function. In inflammatory bowel disease, mononuclear phagocytes showed only a slight increase in CD11a expression and no significant change in expression of CD11b and CD11c. By contrast, the percentage of mononuclear phagocytes expressing intercellular adhesion molecule 1 was increased from 6.9% +/- 3.9% in controls to 69.2% +/- 12.8% in ulcerative colitis (P less than 0.001) and to 45.7% +/- 22.8% in Crohn's disease (P less than 0.01), showing a close relationship with histological activity. The increased expression of intercellular adhesion molecule 1 in inflammatory bowel disease indicates a state of immunological activation induced by local release of inflammatory cytokines. Such induction of intercellular adhesion molecule 1 on mononuclear phagocytes may be important in the maintenance of chronic inflammation by facilitating interactions with T cells and T-cell antigen recognition.
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PMID:Expression of leukocyte adhesion molecules by mucosal mononuclear phagocytes in inflammatory bowel disease. 167 May 78

Neutrophil accumulation is a hallmark of the inflammatory process. The ability of neutrophils to release lipid mediators, toxic oxygen metabolites, proteolytic enzymes and cationic proteins may contribute to the tissue pathology seen in inflammatory diseases such as inflammatory bowel disease and psoriasis. The first step in the process of neutrophil diapedesis in a gradient of chemoattraction is adhesion to the microvascular endothelium, a phenomenon mediated by the stimulated activation of the neutrophil CD11a-c/CD18 cell surface glycoprotein complex. We assessed the ability of a monoclonal antibody (MoAb) (hybridoma: SP2/0-Ag. 14XBALB/c spleen cells; isotype: murine IgG1) to CD18 that recognizes the beta chain of LFA1(CD11a/CD18), MAC-1(CD11b/CD18) and CD11c/CD18 to effect the neutrophils response to the proinflammatory chemotaxins leukotriene B4 (LTB4) and 12(R)-hydroxy-5,8,11,14-eicosatetraenoic acid [12(R)-HETE] in the mouse dermis. LTB4 and 12(R)-HETE induce a time and concentration dependent infiltration of s when applied intradermally. LTB4 (100 ng) and 12(R)-HETE (50 micrograms) were injected intradermally in CD-mice (18 g body weight) and assessed for chemotactic activity four h later by the dermal levels of myeloperoxidase (MPO), a neutrophil marker enzyme. CD18 MoAb(0.02 mg) was given intravenously 10 min ahead of dermal chemotaxin injection. LTB4 increased (p less than .01) dermal levels of MPO at 4 h, a neutrophil accumulation inhibited (p less than .005) by CD18 MoAb pretreatment (Mean MPO +/- SEM: Vehicle, 0.049 +/- 0.006U vs LTB4, 0.309 +/- 0.033U vs MoAb, 0.137 +/- 0.012U) (n = 12/group).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:CD 18 monoclonal antibody inhibits neutrophil diapedesis in the murine dermis induced by leukotriene B4 and 12(R)-hydroxyeicosatetraenoic acid. 197 85

The influx of monocytes and neutrophils into the inflamed tissue could be an important aspect in the pathogenesis of inflammatory bowel disease (IBD). A membrane protein involved in the monocyte/neutrophil adherence to endothelium is CD11b/CD18 or alpha M beta 2 (complement receptor type 3 = CR3). In the present study the role of CD11b/CD18 in experimental IBD was studied by treatment with ED7 and OX42, two MoAbs against CD11b/CD18. Colitis was induced in rats by a single, rectal administration of 30 mg 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol 30%. Two hours before and 3 days after induction of colitis, the animals were given an i.v. dose of 0.5 mg of either ED7 or OX42 in 1 ml PBS. Controls received PBS or an irrelevant MoAb. Four days after the last treatment with the antibodies, the rats were killed, and macroscopic damage scores of the colon were determined. Macrophages and granulocytes were studied by immunohistochemistry and quantified by Interaktives Bild Analysen System (IBAS), and myeloperoxidase (MPO) activity in colonic tissue was measured. After treatment with ED7 and OX42 the mean damage score of the colon was reduced from 4.2 in IBD animals to 1.0 and 1.3, respectively. Smaller areas of ulcerations and a decrease in the number of ulcerations were observed compared with PBS-treated rats. Furthermore, the amount of infiltrating monocytes and leucocytes in the submucosa was enormously reduced, as well as MPO activity in the colonic tissue. These results show that treatment with MoAbs against CD11b/CD18 reduces clinical signs of experimental IBD in rats by a partial blockade of infiltrating macrophages and granulocytes.
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PMID:Anti-CD11b/CD18 antibodies reduce inflammation in acute colitis in rats. 764 20

The effects of the cytokine tumour necrosis factor alpha and the calcium ionophore A23187 upon CD11a, CD11b, CD11c and CD18 leucocyte membrane expression was analysed in whole blood using monoclonal antibodies and flow cytometry. Both agents significantly increased the density of CD11b/CD18 membrane expression on monocytes and granulocytes, but had no effects on adhesion molecule expression on lymphocytes. The effects of sulphasalazine, 5-aminosalicylic acid (5-ASA) and sulphapyridine upon adhesion molecule upregulation were then examined; 10(-3) and 10(-4) M sulphasalazine and 5-ASA significantly reduced tumour necrosis factor alpha induced CD11b/CD18 upregulation on monocytes and granulocytes but had no effects upon A23187 mediated upregulation. Sulphapyridine was inactive. These results suggest that sulphasalazine and 5-ASA may interfere with mechanisms of leucocyte recruitment in inflammatory bowel disease.
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PMID:Inhibition of leucocyte adhesion molecule upregulation by tumor necrosis factor alpha: a novel mechanism of action of sulphasalazine. 809 64

Mucosal inflammation is associated with altered expression of cell membrane molecules. Disaggregation of tissue for flow cytometry may introduce artefactual changes. In an attempt to prevent the induction of artefacts, cells were fixed prior to isolation. The addition of 0.1% buffered formaldehyde to the collagenase/dispase digestion of mucosal biopsy specimens from patients with inflammatory bowel disease enhances detection of CD3, CD11b, CD16, CD63, and CD14. No significant effect was noted for CD19, CD67 or CD45. The expression of CD3, CD11b and CD45 correlated with the degree of endoscopic inflammation. Dilute buffered formaldehyde may be a useful adjunct to the enzymatic isolation of cells from mucosal specimens, by protecting surface antigens from digestion or alterations in expression.
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PMID:Use of buffered formaldehyde in the enzymatic digestion of inflamed mucosa. 865 91

The aims of this study were to investigate whether labelling with technetium-99m exametazime alters the expression of adhesion molecule CD11b on granulocytes and monocytes, and to study whether the expression of CD11b on unlabelled or labelled cells correlates with uptake of the labelled cells in the inflamed bowel, in the lungs or in the reticuloendothelial system. Leucocytes were obtained from 25 patients with inflammatory bowel disease who underwent leucocyte scan. The cellular expression of CD11b was analysed using flow cytometry. Labelling with 99mTc-exametazime induced an increased surface expression of CD11b on granulocytes (P<0.01), but not on monocytes. The increase in CD11b expression on granulocytes was lower than the spontaneous mobilization that occurred at 37 degrees C and correlated neither with this, nor with N-formyl-methionyl-phenylalanine induced expression of the same receptor. Basal expression of CD11b on unlabelled granulocytes, but not on monocytes, correlated with bowel and lung uptake 45 min after reinjection of labelled cells, but not with uptake on later images. No correlation was found between the CD11b expression on labelled granulocytes or monocytes and scintigraphic uptake. Our findings show that labelling with 99mTc-exametazime increases the expression of adhesion protein CD11b on granulocytes. The increase in surface expression of CD11b does not correlate with the scintigraphic uptake of labelled cells in the bowel, in the lungs or in the reticuloendothelial system.
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PMID:Labelling of leucocytes with technetium-99m exametazime causes in vitro upregulation of granulocyte CD11b without correlation to tissue uptake in vivo. 866 1

The production of reactive oxygen species may have an important role in the pathogenesis of inflammatory bowel disease, yet the cells responsible in colonic mucosa have not been clearly defined. We studied 28 patients with ulcerative colitis and 13 controls to determine the cells generating reactive oxygen species, using a combined method for determining nitroblue tetrazolium reducing activity and immunohistochemical characterization. In contrast to the proportion of EBM11-positive cells (tissue macrophages), which did not increase in inflamed mucosa, the proportions of PMN-13F6 positive cells, CD11b-positive cells, and eosinophils were significantly increased in inflamed mucosa. PMN-13F6 positive cell and eosinophil counts were significantly correlated with CD11b positivity. Eosinophils, however, showed a stronger correlation with CD11b positivity than PMN-13F6-positive cells. The majority of CD11b-positive cells were eosinophils. Although some nitroblue tetrazolium reducing leukocytes were positively stained with EBM11 or PMN-13F6, eosinophils were the major subset of nitroblue tetrazolium reducing leukocytes. Recruitment and activation of eosinophils may play an important role in the pathogenesis of ulcerative colitis.
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PMID:In situ comparison of phenotypical and functional activity of infiltrating cells in ulcerative colitis mucosa. 877 24

The beta 2 integrin intercellular adhesion molecule (ICAM) adhesion pathway is likely pivotal in the immunopathogenesis of inflammatory bowel disease (IBD). We have undertaken a comprehensive study of peripheral blood lymphocyte (PBL) expression of all beta 2 integrins and ICAMs in patients with IBD using flow cytometry and assessed our data on the basis of IBD diagnosis, disease state of activity, and use of corticosteroids. Blood was collected from patients with Crohn's disease (N = 49), ulcerative colitis (N = 43), and normal control volunteers (N = 15). Mononuclear cells were separated using a Ficoll-Hypaque gradient and prepared for flow cytometry. The data were analyzed for percentage expression, mean fluorescent intensity (MFI) as well as for histogram patterns. The analysis was stratified for disease diagnosis, disease activity level, and for use of prednisone among patients with active disease. There was decreased percentage expression of CD11a, CD18, and ICAM-3 in Crohn's disease and ulcerative colitis compared with normal, but an increased MFI for these molecules among patients with Crohn's disease. Active Crohn's disease showed a greater change in this pattern compared with both inactive disease and active ulcerative colitis. CD11a and CD18 histograms typically had two peaks of expression. The predominance of one peak over the other varied with disease diagnosis and activity. CD11b and alpha d expression patterns were not different in IBD compared with normal. CD11c was not expressed by PBLs and, ICAM-2, typically an endothelial ligand, was expressed on PBLs. There were changes in the expression of beta 2 integrins in IBD, which were more evident in Crohn's disease than ulcerative colitis. We hypothesize that the decreased percentage expression and increased MFI of CD11a, CD18, and ICAM-3 may suggest that cells up-regulate these ligands following activation and are egressing into tissue.
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PMID:Peripheral blood lymphocyte beta 2 integrin and ICAM expression in inflammatory bowel disease. 939 15

A dysregulated local immune defense with a constant influx of leukocytes provides a basis for continuous intestinal inflammation in ulcerative colitis (UC) and Crohn's disease (CD). Cell adhesion molecules are pivotal for the migration of leukocytes from the circulation toward the colonic epithelium. A study quantifying the cells expressing intercellular adhesion molecules (ICAMs), beta2 integrins, and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in the colon was performed to illustrate the leukocyte migration pathway in inflammatory bowel disease. Serial colonic sections (10 UC, 10 CD, and 10 controls) were stained immunohistochemically for ICAM-1, ICAM-2, ICAM-3, CD11a, CD11b, CD18, and PECAM-1. Cell adhesion molecule expression was evaluated quantitatively with reference to topographic localization. In UC, polymorphonuclear leukocytes (PMNs) in contact with the crypt epithelium and in crypt abscesses expressed CD11b. CD tissue was characterized by CD11a-, CD11c-, and ICAM-1-expressing cells. ICAM-1 was detected on endothelial cells, leukocytes, and apical parts of epithelial membranes, whereas ICAM-2 was expressed on basal epithelial membranes. Most infiltrating leukocytes expressed ICAM-3, whereas perivascular mononuclear cells expressed PECAM-1. Interestingly, the epithelial basement membrane in UC stained for CD18. In conclusion, CD11b, CD18, and ICAM-2 seem to be important for PMN transepithelial migration in UC, whereas CD11a, CD11c, ICAM-1, and ICAM-3 seem central in leukocyte locomotion and aggregation in CD. Differentiated upregulation of cell adhesion molecules is suggested to be essential for the diversities between UC and CD.
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PMID:Comparative studies of the colonic in situ expression of intercellular adhesion molecules (ICAM-1, -2, and -3), beta2 integrins (LFA-1, Mac-1, and p150,95), and PECAM-1 in ulcerative colitis and Crohn's disease. 1093 52

Macrophages play a central role during the pathogenesis of inflammation. In normal intestinal mucosa surface expression of typical macrophage markers such as CD14, CD16, CD11b or T-cell co-stimulatory molecules such as CD80 or CD86 is low indicating anergy and low pro-inflammatory activity of these cells. During inflammatory bowel disease (IBD) the mucosa is invaded by a population of macrophages displaying these markers, secreting higher cytokine levels and representing an activated cell population. CD33(+) cells (macrophages) were isolated from normal and Crohn's disease mucosa and mRNA was isolated by polyT magnetic beads. A subtractive screening was performed subtracting mRNA from normal macrophages from those of Crohn's disease macrophages. Oxidative burst activity was determined by flow cytometry. Seventy clones were obtained by the subtractive mRNA screening. Sequencing showed > 99% homology to mRNA of monocyte chemoattractant protein-1 (MCP-1) for three clones. Five clones obtained by subtraction revealed > 99% homology to mRNA of cytochrome b (subunit gp91). Differential expression of the cytochrome b subunit gp91 and the cytosolic NADPH oxidase subunit p67 was confirmed by RT-PCR and 'virtual' Northern blots. The fluorescence ratio of stimulated versus unstimulated cells was 0.9 +/- 0.16 in control macrophages indicating a lack of oxidative burst activity. In Crohn's disease this ratio was significantly increased to 1.80 +/- 0.8 (P = 0.004) confirming the molecular data. In conclusion NADPH oxidase mRNA is down-regulated or absent in macrophages from normal mucosa correlating with a lack of oxidative burst activity. In IBD macrophage-oxidative burst activity is increased and NADPH oxidase mRNA induced. Inhibition of NADPH oxidase could be a new therapeutical target in IBD and reduce mucosal tissue damage in active IBD.
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PMID:Subtractive screening reveals up-regulation of NADPH oxidase expression in Crohn's disease intestinal macrophages. 1147 25


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