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 early inflammatory response during allergic rhinitis and asthma is associated with IgE-mediated mast cell activation and resultant release of primary inflammatory mediators. The late phase reaction is characterized by recruitment, activation and tissue infiltration of leucocyte populations, including T lymphocytes, eosinophils, basophils and neutrophils. T helper type 2 CD4+ cells, a T lymphocyte subset with a distinctive cytokine profile, are thought to regulate the recruitment and activation of other effector cells. This review discusses the results of studies conducted under experimental and natural conditions of allergen exposure, which confirm the presence of eosinophilia, changes in lymphocyte populations, and increased expression of a TH2-cytokine profile in the nasal mucosa following allergen-induced rhinitis, and the alleviation of both clinical symptoms and inflammatory responses by prior treatment with topical fluticasone propionate. Similar effects are demonstrated to occur in the lower airway following allergen challenge in asthma patients, and to be ameliorated by oral corticosteroid therapy. These studies add weight to the argument that asthma and rhinitis share a common pathophysiology characterized by similar inflammatory events, and should both benefit from early preventative treatment with topical corticosteroids.
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PMID:Mechanisms of mucosal inflammation in the nose and lungs. 967 22

The IgE and allergen dependent activation of mast cells via the high affinity IgE receptor (Fc epsilonRI) resulting in the release of inflammatory mediators is critical to the pathogenesis of atopic diseases like bronchial asthma and allergic rhinitis. However, mast cells are also involved in certain IgE-independent biological responses, and recent studies have highlighted the role of mast cells in host defense. In the light of this background, we have discussed our recent data on the immunophenotypic characteristics of nasal mast cells in patients with perennial allergic rhinitis (PAR) and chronic infective rhinitis (CIR) based on the expression of cytokines, the Fc epsilonRI, the cell-bound IgE, as well as the IgE-mediated mediator release (before and after saturation of the IgE receptors). Although nasal mast cells (NMC) from both groups of patients expressed a variety of cytokines, significant differences were observed in the proportion of cytokine expressing cells between PAR and CIR. NMC from PAR patients exhibited increased Fc epsilonRI expression, cell-bound IgE and IgE-mediated mediator release as compared with NMC from CIR patients, even after saturation of the IgE receptors. The density of IgE receptors and IgE molecules in NMC of PAR patients correlated well with the levels of serum IgE, and IL-4 upregulated the expression of the Fc epsilonRI in NMC. Moreover, NMC from PAR patients induced IgE synthesis in B cells. Taken together, these results and the recently demonstrated IgE-induced upregulation of the Fc epsilonRI expression in mast cells suggest critical roles for mast cells in promoting the allergic reaction through an IgE-Fc epsilonRI-mast cell axis.
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PMID:IgE-Fc epsilonRI-mast cell axis in the allergic cycle. 975 81

This study evaluated the effectiviness and the onset of action of levocabastine (CAS 79547-78-7) nasal spray and eyedrops as well as of nedocromil (CAS 69049-74-7) nasal spray and eyedrops in practical relevant circumstances. The study was designed as an open observational study with parallel groups in 10 centres and comprised 102 patients. All patients presented with seasonal allergic rhinitis and evidenced conjunctival symptoms requiring therapy. The patients as well as the investigators were required to rate the symptoms using symptom scores in order to evaluate the effectiveness of the used drugs. The effectiveness according to symptom scores did not differ significantly between investigator's and patient's judgment. Onset of action was within the first hour in 81.6% of the patients treated with levocabastine and in 82.9% of the patients treated with nedocromil. Symptoms were evaluated on a visual analogue scale ranging from 0 to 100. The use of both substances reduced the severity of the reported symptoms by 50% within the first hour. Thus, no significant difference in the onset of action could be observed even though a later onset of action was expected of the stabiliser of mast cell membranes. Both drugs were tolerated well.
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PMID:Onset of action, effectiveness and tolerance of levocabastine and nedocromil in topical therapy of seasonal allergic rhinoconjunctivitis. The Deutsche Rhinitis-Studiengruppe. 979 20

Prostaglandins likewise leukotriens are proinflammatory mediators resulting from metabolic degradation of the arachidonic acid originating from membrane phospholipids. The most important products of enzyme cyclooxygenation of arachidonic acid are prostaglandins D2, E2, F2a, tromboxane A2 and prostacyclin. Prostaglandins express their tissue effects via the five basic receptor types. Within the allergic inflammation activated mast cell synthesizes prostaglandin D2 (first lipid mediator) which has bronchoconstrictive and vasodilating effects and attracts neutrophilic leukocytes. Moreover, it also participates in the late phase reactions, six hours subsequent to the exposure to the allergen. This mediator is also important in pathogenesis of urticaria, allergic rhinitis and allergic bronchial asthma. In addition to prostaglandin D2, prostaglandin F2a and tromboxane A2 also have bronchoconstrictive actions, while prostacyclin and prostaglandin E have bronchodilating effects. Inhalation of prostaglandin E prevents asthmatic attacks caused by allergens, strain, metabisulfite and ameliorates attacks of aspirin asthma, which confirms the hypothesis that aspirin asthma is based on cyclooxigenase inhibition and increased leukotriene production. In patients with atopic dermatitis, prostaglandin E has suppressive effects on Interferon gamma production by Th1 helper cells and increases production of Interleukin 4 by the Th2 cells. Tromboxane A2 plays a certain role in the development of bronchial hyperreactivity and late asthmatic response. Prostaglandins are also important mediators in the pathogenesis of allergic conjunctivitis. Most of nonsteroidal antiinflammatory drugs inhibit the enzyme cyclooxygenase and thus also prostaglandin biosynthesis and release.
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PMID:[The role of prostaglandins in allergic inflammation]. 986 13

IL-4 is central to the formation of IgE and the development of Th2 effector cells, both key features of an allergic response. We have examined IL-4 production early in the formation of an allergic response by using a previously established human in vivo model of allergic rhinitis where allergic subjects are challenged internasally with allergen and the particulate pollutant diesel exhaust particles (DEP). This model is characterized by enhanced IgE production and deviation to a Th2-type cytokine profile in nasal lavage fluid from these subjects. In this model, IL-4 protein and IL-4-positive cells could first be detected 4 h after challenge and maximal production was observed after 18 h. Two-color flow cytometric analysis for the detection of intracellular IL-4 and surface markers was performed on nasal cells recovered 4 h after challenge. At this time, CD117(+) (c-kit+) cells constituted between 65 and 100% of the IL-4(+) cells, while 0-12% of the IL-4(+) cells were CD3 positive. No IL-4(+) CD19/CD20(+) or IL-4(+) CD56(+) cells were detected at 4 h. As the allergic response progressed the primary source of IL-4 changed. At the peak of IL-4 production, 18 h after challenge, CD3(+) comprised the majority of cells staining for intracellular IL-4 (73 to 100%). Thus we show an initial role for cells of the mast cell/basophil lineage residing in the nasal mucosa in the initial production of IL-4, which frames the subsequent immune response by expanding the repertoire of TH2 cytokine-producing cells in the local microvicinity.
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PMID:Early IL-4 production driving Th2 differentiation in a human in vivo allergic model is mast cell derived. 988 52

The allergic inflammatory response in allergic rhinitis has been studied extensively owing to the high frequency of the condition, the significant morbidity it causes and the accessibility of the nasal tissue. The allergic inflammatory response is characterized by IgE synthesis, IgE-dependent mast cell activation and infiltration of the nasal mucosa by T lymphocytes and eosinophils. The immediate-phase response is mediated by a range of inflammatory mediators (such as histamine, leukotrienes and prostaglandins), resulting in vasodilatation, oedema, mucus secretion, itching and sneezing. Individuals who experience a late-phase response have further nasal symptoms 4-24 h after the initial challenge with allergen. Results of nasal biopsy studies indicate that the late-phase allergic response involves T-lymphocyte activation, production of TH2-type cytokines and tissue eosinophilia. Corticosteroids potently inhibit T-lymphocyte responses, and clinical studies in subjects with allergic rhinitis have demonstrated that they are extremely effective in blocking both early- and late-phase allergic reactions. Topical aqueous triamcinolone acetonide nasal spray represents a novel formulation of a topical corticosteroid for the treatment of allergic rhinitis. Data from controlled clinical studies indicate that it is effective in treating seasonal and perennial disease, is well tolerated, does not suppress adrenocortical function, is odourless, and can be administered as a once-daily dose.
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PMID:The inflammatory nature of allergic disease. 998 30

The characteristics of the "ideal" pharmacotherapeutic agent for managing the symptoms of seasonal allergic rhinitis and the advantages and disadvantages of the pharmacotherapeutic agents that are currently available are reviewed. Decongestants, mast cell stabilizers, anticholinergics, intranasal steroids, and oral antihistamines and their place in the therapeutic armamentarium of the clinician are discussed.
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PMID:Ideal pharmacotherapy for allergic rhinitis. 1006 98

The effects of antigen and histamine on the changes of nasal passage patency in 112 guinea pigs with or without allergic rhinitis were evaluated by acoustic rhinometry. The percent change of volume from the nostril to 2 cm into the nasal cavity showed significant reduction of 31.10 +/- 4.11% at 10 minutes and 31.10 +/- 4.11% at 30 minutes after antigen challenge in sensitized guinea pigs. The pretreatment with ketotifen, an H1-histamine receptor antagonist as well as mast cell stabilizing drug, blocked dose-dependently the effects of antigen on those changes in volume. Furthermore, instillation of 10(4) micrograms/mL histamine reduced significantly nasal passage patency to 33.77 +/- 4.63% at 10 minutes and 42.76 +/- 3.32% at 30 minutes after challenge compared with that before challenge and ketotifen inhibited the effects of histamine, which indicated that histamine is an important mediator of allergic upper airway responses in guinea pigs. These results show that acoustic rhinometry is a useful technique to assess the nasal blockade in allergic guinea pigs.
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PMID:Acoustic rhinometry evaluation of nasal response to histamine and antigen in guinea pigs. 1008 33

Airway allergic reactions enlist diverse cells and a multitude of chemical mediators that are responsible for the clinical symptoms of allergic rhinitis and asthma. Experiments in vitro and in animal models, as well as increasingly numerous studies in atopic human subjects, are revealing that an orchestrated continuum of cellular activities leading to airway allergic inflammation is set in motion in genetically predisposed individuals at the first exposure to a novel antigen. This sensitization step likely depends on differentiation of and cytokine release by T(H)2 lymphocytes. Among T(H)2-derived cytokines, IL-4 potently enhances B-lymphocyte generation of immunoglobulin E antibodies. The attachment of these antibodies to specific receptors on airway mast cells sets the stage for an acute inflammatory response on subsequent antigen exposure because IgE cross-linking by a bound antigen activates mast cells to release numerous inflammatory mediators. These mast cell-derived mediators collectively produce acute-phase clinical symptoms by enhancing vascular leak, bronchospasm, and activation of nociceptive neurons linked to parasympathetic reflexes. Simultaneously, some mast cell mediators up-regulate expression on endothelial cells of adhesion molecules for leukocytes (eosinophils, but also basophils and lymphocytes), which are key elements in the late-phase allergic response. Chemoattractant molecules released during the acute phase draw these leukocytes to airways during a relatively symptom-free recruitment phase, where they later release a plethora of cytokines and tissue-damaging proteases that herald a second wave of airway inflammatory trauma (late-phase response). The repetition of these processes, with the possible establishment in airway mucosa of memory T lymphocytes and eosinophils that are maintained by paracrine and autocrine cytokine stimulation, may account for airway hypersensitivity and chronic airway symptoms.
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PMID:Pathophysiology of the inflammatory response. 1051 9

Nasal mucosa is heavily exposed to inflammatory and allergic stimuli, rhinitis being the most common form of allergic respiratory disease. The nose is an easily accessible organ and a good model for the study of allergies as it makes it possible to monitor the effects of specific challenges as well as therapeutic interventions, namely specific immunotherapy (SIT). Injectable, nasal or sublingual SIT are useful therapeutic strategies in the management of allergic rhinitis patients. Monitoring the evolution of parameters such as clinical scores, nasal peak flow variation or drug requirements during SIT provides important information on its clinical efficacy. Laboratory measurement of tryptase and eosinophil cationic protein in the target organ after specific nasal provocation makes it possible to record changes in the release of mast cell and eosinophil mediators, thus providing objective evidence of the immunological efficacy of this therapy on these cell populations and providing data which eventually will contribute to a better understanding of the multiple mechanisms of action of allergen desensitization therapy.
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PMID:Nasal provocation and immunotherapy. 1058 95


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