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)

The effects of ketotifen, a 'mast cell stabiliser,' on two models of experimental colitis were examined. The inflammatory response elicited by either trinitrobenzene sulphonic acid or acetic acid resulted in increased colonic synthesis of platelet activating factor, prostaglandin E2, thromboxane B2, leukotrienes B4 and C4, and myeloperoxidase activity. Intragastric administration of ketotifen 100 micrograms/100 grams twice daily significantly decreased mucosal damage when given prophylactically 48 hours before the induction of colitis and then throughout the experiment. This effect was consistent in both models and was accompanied by a significant reduction in mucosal generation of platelet activating factor, prostaglandin E2, thromboxane B2, and leukotrienes C4 and B4. Myeloperoxidase activity was reduced as well, reaching significance only in the acetic acid model. This study shows that both trinitrobenzene sulphonic acid and acetic acid colitis can be pharmacologically manipulated by ketotifen. The mechanism of action of ketotifen has not yet been determined. Ketotifen's potential in the treatment of active inflammatory bowel disease or in the prevention of exacertations, or both, remains to be elucidated.
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PMID:Ketotifen effectively prevents mucosal damage in experimental colitis. 145 75

Mast cell-endothelial cell interactions have long been suspected to be important in inflammation. The detail of the pathways of communication have yet to be elucidated. In this report we describe, for the first time, mast cell granules within endothelial cells of colonic capillaries in a patient with florid colitis, as well as rats with experimentally induced mast cell degranulation. We postulate that this phenomenon may occur more generally during immunologically mediated inflammatory cell degranulation, and may be one mechanism of communication to endothelium.
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PMID:Mast cell granules within endothelial cells: a possible signal in the inflammatory process? 149 40

Mast cell alterations have been implicated in the pathogenesis of chronic ulcerative colitis (UC). We studied the effect of mast cell deficiency of the severity of inflammation in a murine model of colitis. Colitis was induced in mice using dextran sodium sulfate (DSS). Mast-cell-deficient mice (WBB6F1/J-W/WV; N = 17) and normal littermates (WBB6F1/J-+/+; N = 17) were administered DSS 4% w/v for seven days, then water alone for one week, followed by 5% DSS for six days. Animals were sacrificed at the end of the protocol. Segments of proximal, mid-, and distal colon of each animal were processed for histopathological examination. Mortality and morbidity (diarrhea and weight loss) for each group were assessed. There was no significant difference between the two groups in either their clinical parameters (mortality and morbidity) or the severity of colitis as graded histopathologically. Our findings suggest that mast cells are not crucial for the development of DSS-induced colitis.
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PMID:Lack of crucial role of mast cells in pathogenesis of experimental colitis in mice. 764 76

The severity and consequences of human Trichuris infection vary widely. This may reflect differences in immune response. T. muris is a natural parasite of mice which provides a close, well defined, easily manipulated model for otherwise uninvestigatable aspects of this response. Normal mice reject the parasite in 3 weeks, but mice subjected to transient immunosuppression around the time of infection develop a persistent caecal infection. Sequential histopathological studies have shown that infected, normal mice develop a marked intraepithelial, mucosal, 'globule leucocyte' response, accompanied by low-level lymphocytic and histiocytic responses in the lamina propria. The reaction is maximal at 3 weeks and declines towards normal after rejection. Infected, immunosuppressed mice show a slower response with, by weeks 4 and 5, fewer 'globule leucocytes', but a chronic colitis comprising heavy, mixed, mucosal and submucosal inflammation and crypt damage accompanied by persistent parasite infection. The 'globule leucocyte' has been characterized by cytochemistry and electron microscopy as having a mast cell origin. This study, with other evidence, suggests that the replacement of a Th2 (allergic) T helper cell response by a Th1 (cell-mediated) response may result in increased severity and persistence of colitis in response to Trichuris infection.
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PMID:Immunoepidemiology of intestinal helminth infections. 4. Immunopathology in trichuriasis: lessons from the mouse model. 797 60

Dietary protein-induced colitis is a frequent cause of rectal bleeding in infants. The exact pathogenic mechanism is unknown but the disorder has been thought to be due to an allergic response. Rectal mucosal edema and eosinophilia are typically found but there are no specific markers currently available. Because eosinophil degranulation, as evidenced by the release of major basic protein, has been implicated in hypersensitivity disorders, we aimed to assess major basic protein deposition as a marker of dietary protein-induced colitis occurring in young infants. Suction rectal biopsies from five infants aged 1 to 7 months with findings consistent with dietary protein-induced colitis were compared histologically with five age matched controls who underwent rectal biopsies to rule out Hirschsprung's disease. An established indirect immunofluorescent staining method was used to identify tissue major basic protein. Comparable rectal deposition of major basic protein was found for the controls and colitic patients. Mucosal eosinophilia but not mast cell content was more prominent in the colitic patients (P < .05) than in the controls. Some of the colitic infants had elevated serum IgE levels (1 of 5), positive RAST for milk (2 of 5), and peripheral blood eosinophilia (1 of 5). Our findings do not support the concept that dietary protein-induced colitis of infancy is due solely to an immediate hypersensitivity response. The results also indicate that major basic protein is probably not a marker or likely primary mediator of this disorder.
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PMID:Rectal mucosal major basic protein in infants with dietary protein-induced colitis. 832 17

We examined the possible involvement of mast cells in a rat model of colitis, by monitoring levels of histamine at various times after inducing inflammation with intrarectal trinitrobenzene sulfonic acid in 50% ethanol. The ability of a histamine H1 antagonist, diphenhydramine, to modify colitis was also assessed. As expected, trinitrobenzene sulfonic acid in 50% ethanol induced a sustained colitis. Myeloperoxidase levels in macroscopically damaged tissue peaked at one week, and declined thereafter. In contrast, tissue histamine levels were normal at one week, then increased in damaged tissue to approximately four times normal levels at four weeks. Indices of inflammation were markedly suppressed at one week by diphenhydramine, while tissue histamine levels were unaffected. Chronic colitis in rats is thus apparently accompanied by a local mast cell hyperplasia or influx. Moreover, antagonism of a major mast cell mediator, histamine, significantly reduces the severity of inflammation in this model.
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PMID:Role of histamine in a rat model of colitis. 884 97

The objective was to characterize changes in barrier and transport function in an experimental model of colitis, and to determine whether mast cells contribute to these changes. Colitis was induced in rats with intracolonic 2,4,6-trinitrobenzenesulfonic acid (TNBS, 30 mg) in 50% ethanol. Controls received 0.9% saline or the ethanol vehicle alone. In vivo loop perfusion was used to assess colonic water flux (in microliter.cm-1.h-1) and lumen-to-blood 51Cr-labeled EDTA clearance (% administered dose) after TNBS. Myeloperoxidase (MPO) was used as an index of granulocyte influx. TNBS or its vehicle caused a marked decrease in water absorption and an increase in permeability at 4 h after administration compared with saline. Neither dexamethasone (anti-inflammatory control) nor doxantrazole (mast cell stabilizer) was able to attenuate these early changes likely caused by the vehicle. In contrast, at later times, TNBS (but not its vehicle) also increased 51Cr-EDTA permeability and decreased water absorption; both effects were significantly attenuated by dexamethasone or doxantrazole. These drugs also significantly reduced TNBS-induced MPO accumulation and release of rat mast cell protease II. We conclude that experimental colitis is associated with severe defects in intestinal transport and barrier functions and that mast cells may contribute to the pathogenesis of these changes.
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PMID:Disruption of intestinal barrier function associated with experimental colitis: possible role of mast cells. 945 91

Eosinophils contribute to the inflammatory process in a variety of chronic inflammatory bowel diseases. Ketotifen is beneficial in experimental models of colitis and in patients with eosinophilic gastroenteritis. Therefore, we investigated the efficacy of ketotifen therapy for the treatment of active ulcerative colitis. Children with newly or previously diagnosed ulcerative colitis with mild-moderate disease activity were treated with ketotifen at a dosage of 4 mg daily for eight weeks. Efficacy was determined by a physician disease severity index and by endoscopic and histologic examinations. Ten patients were enrolled. Symptoms improved in four patients and resolved completely in one patient. There was endoscopic improvement in three patients and histologic improvement in one. Increased eosinophils on rectal biopsy at entry were present in two of the responders. Five patients withdrew due to a lack of symptomatic improvement. No adverse events were identified. Low-dose ketotifen offers a limited therapeutic advantage in active ulcerative colitis that may be enhanced in the subgroup of patients with a high eosinophil count in the colonic mucosa. Further study of therapeutic efficacy with increased dosages of the mast cell stabilizer for acute and maintenance therapy is warranted.
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PMID:Ketotifen therapy for acute ulcerative colitis in children: a pilot study. 953 58

Mast cell stabilizers are commonly used in the treatment of asthma and allergic disorders. Although the role of mucosal mast cells in the pathogenesis of inflammatory bowel disease remains uncertain, mast cell stabilizers have been shown in animal models to attenuate the severity of experimental colitis. The authors' experience with ketotifen in three patients--one each with Crohn's disease, ulcerative colitis and collagenous colitis--who had demonstrated allergy to, or intolerance of, 5-aminosalicylic acid is reported.
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PMID:Ketotifen treatment of active colitis in patients with 5-aminosalicylate intolerance. 965 66

To assess the possible involvement of mast cells and/or their mediators in inflammatory bowel diseases, the effect of the histamine H1 antagonist Dithiaden was studied on a model of acetic acid-induced colitis in rats. Dithiaden pretreatment by intracolonic administration was found to reduce the extent of acute inflammatory colonic injury. This was manifested by a decrease in the score of gross mucosal injury, by lowered colonic wet weight and by diminished myeloperoxidase activity reflecting reduced leukocyte infiltration. Vascular permeability and gamma-glutamyl transpeptidase activity, elevated by acetic acid exposure, were decreased after Dithiaden pretreatment. The results indicate that locally administered Dithiaden may protect the colonic mucosa against an acute inflammatory attack by interfering with the action of the major mast cell mediator histamine.
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PMID:Effects of histamine H1 antagonist dithiaden on acetic acid-induced colitis in rats. 1047 Aug 68


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