Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous reports indicate that intestinal intraluminal ethanol increases mucosal permeability (an index of mucosal injury) and histamine release by mast cells, and that the released histamine plays a role in mediating the increased permeability. In the present study, we investigated whether reactive oxygen metabolites and their major sources (xanthine oxidase and leukocytes) were involved in these ethanol effects. In rabbits, segments of the jejunum were perfused with a control solution or with 6% ethanol. In these segments, mucosal permeability was assessed by determining jejunal clearance of i.v. administered 51Cr-ethylenediaminetetraacetate (51Cr-EDTA) and 125I-bovine serum albumin (125I-BSA), and mast cell histamine release was estimated from the histamine concentration of the gut effluent. Ethanol increased 51Cr-EDTA clearance, 125I-BSA clearance, and histamine release. These ethanol effects decreased when the animals were given superoxide dismutase plus catalase (scavenger of O2- and H2O2, respectively), allopurinol, or oxypurinol (xanthine oxidase inhibitors). Administration of a monoclonal antibody (R15.7) against leukocyte adhesion molecule, CD18, inhibited completely the ethanol-induced increased 51Cr-EDTA and 125I-BSA clearances and histamine release. These and supplementary data suggest that (a) ethanol-induced mucosal injury and mast cell histamine release are mediated primarily by leukocytes, and (b) oxy radicals, especially those generated by xanthine oxidase, mediate these ethanol effects mainly by promoting leukocyte infiltration.
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PMID:Role of xanthine oxidase-derived oxidants and leukocytes in ethanol-induced jejunal mucosal injury. 901 59

Mast cells are bone marrow-derived, ubiquitous connective tissue resident cells. However, their mechanisms of migration, the distribution of immature and mature cells and their interaction with other inflammatory cells are largely unclarified. Possibly, beta 2-integrins play an important role in these processes. In the present investigation, the authors studied the expression and regulation of the beta 2-integrins LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18), p150,95 (CD11c/CD18) and of the LFA-1/Mac-1 counter-receptor intercellular adhesion molecule-1 (ICAM-1; CD54) on leukaemic (HMC-1 cell subclone 5C6) and on normal mature human skin mast cells. The HMC-1 cells clearly expressed CD11a, CD18 and CD54, while expression of CD11b and CD11c was low. The apparent molecular weights were 180 kDa (CD11a), 95 kDa (CD18) and 90 kDa (CD54) as determined by Western blot analysis. Phorbol myristate acetate (PMA) induced a time- and dose-dependent up-regulation of CD11a, CD11b, CD11c, CD18 and CD54 that was inhibited by cycloheximide, suggesting a dependence on de novo protein synthesis. Enhanced expression of CD11a, CD11b, CD11c and CD18 could also be confirmed at the gene level as demonstrated by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Increased expression of LFA-1/ICAM-1 in response to PMA was accompanied by strong enhancement of homotypic cell aggregation, suggesting that newly synthesized LFA-1/ICAM-1 is functionally active. In order to determine a physiologically relevant way of mast cell beta 2-integrin modulation, several cytokines and chemotactic mediators (interleukin-4, IL-4; nerve growth factor beta, NGF beta; C5a; and leukotriene B4, LTB4) were tested for their influence on adhesion molecule cell surface density. Only LTB4 was shown specifically to up-regulate CD11a and CD18, but not CD11b or CD11c. The presence of CD11a, CD11c and CD18 could be confirmed on a low percentage of normal skin mast cells by immunofluorescence, using a double staining technique. In comparison to normal skin, a significantly higher percentage of CD18+ mast cells was found in inflammatory dermatoses such as psoriasis vulgaris, atopic dermatitis and lichen planus. Therefore, mast cell beta 2-integrins possibly play an important role during homing of immature mast cells as well as during the interaction of activated mast cells with other inflammatory cells.
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PMID:Human leukaemic (HMC-1) and normal skin mast cells express beta 2-integrins: characterization of beta 2-integrins and ICAM-1 on HMC-1 cells. 916 89

Dietary copper has long been known to be essential for cardiovascular homeostasis. However, the role of copper and cuproenzymes in the normal control of vascular physiology is not well understood. Most studies in the cardiovascular system have focused on copper deficiency-induced defects in the heart or large vessels. Recently, attention has also focused on the effects of copper deficiency in the microcirculation or the small blood vessels that control blood flow, nutrient and waste exchange, and peripheral vascular resistance. Studies in the microcirculation demonstrate that copper is important in mechanisms of macromolecular leakage, platelet-endothelial interactions and vascular smooth muscle reactivity. There is a significantly greater leakage of proteins from postcapillary venules in copper-deficient rats in response to mast cell-released histamine. This response appears to be the result of increased numbers of mast cells and thereby increased available histamine. Copper deficiency also causes an inhibition of in vivo thrombogenesis, which appears to be related to an inhibition of platelet adhesion. Subsequent studies have demonstrated that this is probably caused by a diminished concentration of the adhesion molecule von Willebrand factor. Nitric oxide (NO)-mediated arteriole vasodilation is also compromised in copper-deficient rats. This functional deficit to NO can be reversed by the addition of Cu, Zn-superoxide dismutase (SOD), suggesting that degradation of NO by superoxide anion occurs during copper deprivation. These observations demonstrate that dietary copper is necessary for several microvascular control mechanisms affecting inflammation, microhemostasis and regulation of peripheral blood flow.
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PMID:Dietary copper in the physiology of the microcirculation. 940 74

The dual radiolabeled monoclonal antibody technique was used to 1) define the magnitude and kinetics of P-selectin expression in murine small intestine exposed to ischemia-reperfusion (I/R), and 2) determine the factor(s) responsible for initiating this response. Within 10 min after release of a 20-min arterial occlusion, intestinal P-selectin expression increased two- to threefold compared with control values. Peak (4-fold) expression of P-selectin was noted at 5 h after reperfusion, returning to the control value at 24 h. The early (10-30 min) I/R-induced upregulation of P-selectin appears to reflect mobilization of a performed pool of the adhesion molecule, whereas the later (5 h) rise appears to be transcription dependent. The early increase in P-selectin expression was not inhibited by pretreatment with either oxypurinol (inhibits xanthine oxidase), diphenhydramine (H1-receptor antagonist), or MK-571 (leukotriene C4/D4 antagonist), nor was it blunted in transgenic mice expressing three times the normal level of copper-zinc superoxide dismutase or in mast cell-deficient mice. However, significant inhibition was noted after treatment with either MK-886 (5-lipoxygenase inhibitor) or a nitric oxide (NO) donor (diethylenetriamine/NO). These findings indicate that the early I/R-induced increase in intestinal P-selectin expression is mediated by a 5-lipoxygenase-dependent NO-inhibitable mechanism.
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PMID:Modulation of P-selectin expression in the postischemic intestinal microvasculature. 943 58

Local inhibition of nitric oxide (NO) synthesis with L-arginine analogs such as NG-nitro-L-arginine methyl ester (L-NAME) decreased red blood cell velocity (VRBC) in capillaries and increased leukocyte adhesion in postcapillary venules in rat skeletal muscle. The goal of the present study was to determine the mechanism of this response to L-NAME. Using intravital videomicroscopy, we examined blood flow in the surface microvasculature of rat extensor digitorum longus muscle. L-NAME (30 mM in the pipette) locally applied to capillaries (300 microns from feeding arteriole) reduced VRBC [control VRBC = 244 +/- 53 (SE) microns/s; delta VRBC = -52 +/- 8%] and increased leukocyte adhesion (from 0.2 +/- 0.01 to 1.3 +/- 0.3 cells/100 microns) in control animals. Systemic pretreatment with fucoidan (selectin binder), superoxide dismutase and catalase (extracellular antioxidants), dimethylthiourea (intracellular antioxidant), or ketotifen (mast cell stabilizer) did not alter this response. Pretreatment with CL26, an anti-CD18 antibody, abolished the L-NAME response. Our results suggest that L-NAME increased leukocyte-endothelial interactions via an effect on CD11/CD18 or its ligand, intercellular adhesion molecule.
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PMID:Local L-NAME decreases blood flow and increases leukocyte adhesion via CD18. 957 30

This study sought to clarify the early events occurring within the airways of healthy human subjects performing moderate intermittent exercise following ozone challenge. Thirteen healthy nonsmoking subjects were exposed in a single blinded, crossover control fashion to 0.2 parts per million (ppm) O3 and filtered air for 2 h, using a standard intermittent exercise and rest protocol. Lung function was assessed pre- and immediately post-exposure. Bronchoscopy was performed with endobronchial mucosal biopsies, bronchial wash (BW) and bronchoalveolar lavage (BAL) 1.5 h after the end of the exposure period. Respiratory tract lining fluid (RTLF) redox status was assessed by measuring a range of antioxidants and oxidative damage markers in BW and BAL fluid samples. There was a significant upregulation after O3 exposure in the expression of vascular endothelial P-selectin (p<0.005) and intercellular adhesion molecule-1 (p<0.005). This was associated with a 2-fold increase in submucosal mast cells (p<0.005) in biopsy samples, without evidence of neutrophilic inflammation, and a decrease in BAL fluid macrophage numbers (1.6-fold, p<0.005), with an activation of the remaining macrophage subset (2.5-fold increase in % human leukocyte antigen (HLA)-DR+ cells, p<0.005). In addition, exposure led to a 4.5-fold and 3.1-fold increase of reduced glutathione (GSH) concentrations, in BW and BAL fluid respectively (p<0.05), with alterations in urate and alpha-tocopherol plasma/RTLF partitioning ratios (p<0.05). Spirometry showed reductions in forced vital capacity (p<0.05) and forced expiratory volume in one second (p<0.01), with evidence of small airway narrowing using forced expiratory flow values (p<0.005). Evidence was found of O3-induced early adhesion molecule upregulation, increased submucosal mast cell numbers and alterations to the respiratory tract lining fluid redox status. No clear relationship was demonstrable between changes in these early markers and the lung function decrements observed. The results therefore indicate that the initial lung function decrements are not predictive of, or causally related to the O3-induced inflammatory events in normal human subjects.
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PMID:Ozone-induced lung function decrements do not correlate with early airway inflammatory or antioxidant responses. 1044 22

It has been reported that infection with Nippostrongylus brasiliensis induces villus atrophy with various histological alterations. In N. brasiliensis-infected rats, villus length in the jejunum was reduced significantly at day 10 p.i., when serum levels of rat mast cell protease (RMCP) II had increased significantly. To determine whether the villus atrophy is associated with enhancement of apoptosis, apoptotic nuclei were labelled using the nick end-labelling method. Numbers of labelled cells were markedly increased in the villus epithelium at 7-10 days p.i., while the numbers returned to normal 14 days p.i. when worms were rejected from the intestine and villus length became normal. Examination of the expression of the adhesion molecule E-cadherin showed granular immunoreactivity in the cytoplasm of atrophic villus epithelium with loss of normal localization to epithelial cell borders. In mast cell-deficient Ws/Ws rats, villus length was reduced as significantly as in +/+ counterparts at day 10 p.i. with marked increases in the numbers of apoptotic cells. These results suggested that villus atrophy was closely associated with enhanced apoptosis and loss of adhesion in epithelial cells. Mast cell activation appears not to be involved in these alterations.
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PMID:Enhancement of apoptosis with loss of cellular adherence in the villus epithelium of the small intestine after infection with the nematode Nippostrongylus brasiliensis in rats. 1046 28

In addition to being a major effector cell in the elicitation of allergic inflammation, mast cells have been found to be activated in various T cell-mediated inflammatory processes and to reside in close physical proximity to T cells. Such observations and the wide spectrum of mediators produced and secreted by mast cells have led investigators to propose a functional relationship between these 2 cell populations. Indeed, mast cell activation has been reported to induce T-cell migration either directly by the release of chemotactic factors, such as lymphotactin or IL-16, or indirectly by the induction of adhesion molecule expression on endothelial cells. Mast cells are also able to present antigens to T cells, resulting in their activation in either an MHC class I- or class II-restricted and costimulatory molecule-dependent fashion. Adhesion molecule-dependent intercellular contact or MHC class II cognate interactions between T cells and mast cells result in the release of both granule-associated mediators and cytokines from the latter. Also, T cell-derived mediators, such as beta-chemokines, directly induce mast cell degranulation. On the other hand, mast cell-derived cytokines, such as IL-4, have been found to polarize T cells to preferentially differentiate into the T(H2) subset. Thus T cell-mast cell interactions are bidirectional, fulfilling regulatory and/or modulatory roles affecting various aspects of the immune response.
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PMID:Mast cell-T cell interactions. 1048 20

Sulfasalazine and 5-aminosalicylic acid are very useful therapeutic agents for the treatment of the inflammatory bowel disease, such as ulcerative colitis or Crohn's disease. However, the mechanism of action of the aminosalicylates remains obscure. Recently, many studies about their mechanism have been performed. As a result, aminosalicylates have been identified to have several antiinflammatory pathways: (1) alterations in eicosanoid metabolism of arachidonic acid; particularly inhibition of leukotrien B4 production, (2)free radical scavengers; scavenging reactive oxygen metabolites or nitric oxide (3)immunologic suppression; inhibition of HLA-DR expression on the intestinal epithelial cells, inflammatory cytokine(IL-1 and IL-2) production, adhesion molecule expression, platelet-activating factor release, or histamine release from mast cell, and so on.
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PMID:[Salazosulfapyridine and 5-aminosalicylic acid agents for the treatment of ulcerative colitis]. 1057 15

Intercellular adhesion molecule-3 (ICAM-3, CD50), an adhesion receptor of the immunoglobulin superfamily, is suggested to play a key role in adhesive cellular interactions during the initial phase of an immune response. We here provide evidence that ICAM-3 is abundantly expressed by cells of the human mast cell line HMC-1 and, to a lower degree, by purified skin mast cells, as demonstrated by flow-cytometry, ELISA and RT-PCR. ICAM-3 immunoprecipitated from surface biotinylated HMC-1 cells migrates as a broad band of Mr 124,000 by Western blot analysis. We also demonstrate that monoclonal antibodies directed against ICAM-3 are capable of inducing rapid HMC-1 cell aggregation, the extent of which strongly depends on the epitope recognized by the mAb applied. Interestingly, although inhibitable by two of six mAbs against LFA-1, HMC-1 aggregation induced via ICAM-3 appears to be mediated by an adhesive pathway independent of LFA-1. Dermal mast cells are also aggregated with anti-ICAM-3 mAbs, a phenomenon which has not been described before for isolated tissue mast cells. However, this process displays slower kinetics, as compared to HMC-1 cells. That anti-ICAM-3 mAbs are able to mediate biological effects is further illustrated by their capability to increase stimulation-dependent release of the pro-inflammatory cytokines interleukin-6 (IL-6) and IL-8 from HMC-1 cells. Taken together, these results indicate that ICAM-3 is not only expressed by immature and mature human mast cells, but also possesses functional relevance and may therefore play a significant role in mast cell associated processes.
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PMID:ICAM-3 (CD50) is expressed by human mast cells: induction of homotypic mast cell aggregation via ICAM-3. 1062 4


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