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)

Despite the varied immunological changes occurring after allergen immunotherapy, the precise mechanism, or the mechanisms responsible for clinical effectiveness of allergen immunotherapy have not been clearly determined. Postulated immunomodulatory mechanisms include a decrease in cellular responsiveness, a production of blocking antibodies, a reduction in the number of mast cells, and activation of T-cell suppressor mechanisms. Nineteen allergic rhinitis patients (study group) with house dust mite sensitivity and 10 nonallergic control subjects were studied. In the study group, the nasal mucosal biopsies were obtained prior to immunotherapy and were repeated after 1 year, and specimens were evaluated by light and electron microscopy. After the third month of immunotherapy, nasal symptom scores were reduced significantly and disappeared in the sixth month (p <0.01). No significant changes were observed in the levels of immunoglobulins, IgG subclasses and complement levels (p <0.05), except IgG4/IgG1 ratio (p <0.05). A comparison of histopathological findings of nasal mucosa in each case revealed an improvement in epithelial loss, inflammation, thickening of basal membrane and fibrosis (p <0.05). A significant correlation was observed between epithelial loss and mast cell accumulation with symptom score (p <0.001). These results suggest that the improvement of nasal epithelial cells and reduction of mast cell accumulation in nasal mucosa may be one of the mechanisms that could explain the improvement of nasal allergy symptoms following immunotherapy.
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PMID:Effects of allergen immunotherapy on the nasal mucosa in patients with allergic rhinitis. 1078 Jul 94

Allergic rhinitis is characterized by an inflammatory reaction consequent to an initial IgE-dependent mast cell activation. The conventional treatment is mainly based on antihistamine and topical corticosteroid prescriptions. In this article the authors consider the antiallergic-antiinflammatory activity exerted by some nonsteroidal drugs or immunologic treatments. Clinical and experimental evidence demonstrates that these treatments are able to control allergic inflammation in patients with allergic rhinitis. In conclusion, treatment of allergic rhinitis may also be based on the prescription of nonsteroidal drugs with antiallergic activity.
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PMID:Nonsteroidal antiallergic treatments in allergic rhinitis. 1106 57

An immunohistochemical study was conducted on the degree of tryptase-positive, chymase-negative mast cells (MCT) and tryptase-positive, chymase-positive mast cells (MCTC) infiltration in the inferior turbinates of 15 patients with perennial allergic rhinitis who underwent septal reconstruction and bilateral inferior turbinectomy 85 +/- 21 days after unilateral chemosurgical treatment using trichloroacetic acid (TCA). In samples without TCA treatment, many MCTs were observed in the mucosal epithelium near the basement membrane, especially in the area where many goblet cells were found, and some MCTs were found around the glands and vessels in the subepithelial layer. Most MCTCs were found in the subepithelial layer, and some in the epithelial layer. On the TCA-treated side, part of the epithelium disappeared, becoming squamatized epithelium in which MCTs were scarcely observed. Statistically, the number of mast cell on the side of TCA treatment was significantly less than on the non-treated side in the epithelial layer. In treated subepithelium layer, both MCTs and MCTCs were significantly fewer than on the non-treated side. These pathological findings suggest that TCA surgery has clinical potential to improve allergic rhinitis symptoms.
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PMID:[Immunohistochemical study of mast cells in allergic rhinitis: an indicator for assessing the therapeutic effect of chemosurgery using trichloroacetic acid]. 1107 Sep 78

HYPOTHESIS: Idiopathic and allergic rhinitics have similar mucosal mast cell and IgE+ cell distribution. INTRODUCTION: The pathophysiology of idiopathic rhinitis (IR) is unknown but patients differ from those with allergic rhinitis (AR) in that they do not express IgE. Our study is novel because we investigated: (1) three study groups chosen prospectively using strict selection criteria over a 4-year period; and (2) mast cell and IgE+ cell counts were on full-thickness, full-length inferior turbinate mucosa. METHODS: Patient groups: allergic (n = 17); idiopathic: (n = 16); and normal controls (n = 9). Immunohistochemistry: mast cell and IgE+ cell detection using anti-mast cell tryptase and anti-IgE antibodies with an avidin-biotin (peroxidase) complex on paraffin processed tissue. Morphometry: sections were divided into three strata comprising an epithelial layer and two submucosal layers. Statistics: Mann-Whitney non-parametric analysis. alpha = 0.05, beta = 0.2. RESULTS: The power of the study was 89%. Mast cells (P = 0.03) and IgE+ cells (P < 0.05) were significantly increased in the epithelium of idiopahtic and allergic rhinitis mucosa compared to the normal control. More IgE+ cells were counted in the AR and IR groups compared to the controls in all three strata. CONCLUSION: Mast cells and IgE+ cells are involved in the pahtophysiology of IR. We propose that IR may be a variant form of AR involving a localized IgE-mediated inflammatory response.
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PMID:Idiopathic and allergic rhinitis show a similar inflammatory response 1112 70

Fel d I is the major cat allergen that induces asthma and allergic rhinitis in humans. To investigate the mechanism of allergic responses to this allergen, a mouse model was developed. Mice sensitized to chain 1 of Fel d I exhibited T cell responses, B cell responses, and mast cell responses when challenged with the protein. Subcutaneous injections of peptides containing the dominant T cell epitopes of the allergen induced T cell tolerance in presensitized mice. When challenged with the allergen intratracheally, these tolerized mice produced a decreased amount of histamine in vivo. The decrease in histamine release was not solely dependent on the reduction of allergen-specific IgE. These data show that mast cell activity in mice with an ongoing sensitivity to allergen can be regulated through peptide-induced T cell tolerance.
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PMID:Antigen-specific T cell tolerance down-regulates mast cell responses in vivo. 1116 43

Mast cells play a central role in the pathogenesis of many allergic disorders. They can be activated in different ways. The present study was focused to evaluate the role of mast cells in acquired chronic urticaria-angioedema induced by gastroesophageal reflux. Tryptase, an important marker of mast cell activation, was detected with UniCap Tryptase Fluoroenzymeimmunoassay (Pharmacia & Upjohn AB, Uppsala, Sweden). Eight subjects were studied: four males and four females, aged between 29 and 71 years (mean age: 45 yrs.), suffering from acquired chronic urticaria-angioedema. Results were compared with the results of seven healthy control subjects. Moreover, data were compared with those of 13 subjects (10 males and 3 females, mean age: 24.7 years) suffering from allergic rhinitis. In acquired chronic urticaria-angioedema, serum tryptase levels (mean +/- S.D.: 9.6 +/- 4.3 microg/l) were significantly higher (P < 0.007) than those of the controls (mean +/- S.D.: 3.0 +/- 1.2 microg/l) and higher also than in allergic rhinitis (mean +/- S.D.: 6.1 +/- 2.4 microg/l, P < 0.03). The results underline the central role of mast cells in the inflammation of acquired chronic urticaria-angioedema.
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PMID:Mast cell activation in acquired chronic urticaria-angioedema. 1132 2

We determined the distribution of mast cells in nasal mucosa and studied their proliferation. Inferior turbinate mucosa was sampled in 13 patients with allergic rhinitis (allergic group) and 5 without (non allergic group) and stained immunohistochemically using anti mast cell tryptase antibody, anti-c-kit antibody, anti-PCNA antibody, and anti mast cell chymase antibody. Tissue sections stained with anti tryptase antibody revealed a higher degree of infiltration of tryptase-positive cells, i.e., mast cells, in the allergic group than in non allergic group. In the allergic group, the number of tryptase-positive cells, c-kit-positive cells, and PCNA-positive cells was significantly greater in the epithelium and shallow lamina propria than that in the deep lamina propria. Tryptase-positive, c-kit-positive cells, i.e., c-kit-positive mast cells, and tryptase-positive, PCNA-positive cells, i.e., PCNA-positive mast cells, were also abundunt in the epithelium and shallow lamina propria. The stem cell factor and c-kit receptor are reported to play a primary role in mast cell differentiation and proliferation. PCNA-positive cells represent actively proliferating cells. Based on the above, we concluded that mast cells in the epithelium and shallow lamina propria in the allergic group differentiated and proliferated more actively than those in the deep lamina propria.
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PMID:[Differentiation and proliferation of mast cells in nasal mucosa]. 1143 40

The mode of action of intranasal corticosteroids (INCS) is complex. It is not known whether INCS penetrate the nasal mucosa or act on target cells; however, their low systemic activity supports the concept of local action on nasal mucosa. This local effect can nonetheless influence a variety of inflammatory cells and their mediators such as epithelial cells, lymphocytes, basophils, mast cells, and Langerhans cells. Corticosteroid-induced inhibition of immunoglobulin E-dependent release of histamine is a possible but unproven mode of action. Epithelial cells are an important target for corticosteroids, and INCS concentration is high at the epithelial surface. INCS may combine with the corticosteroid receptors in epithelial cells, which are then expelled into the airway lumen together with the dead epithelial cells or migrating inflammatory cells. A reduced influx of mediator cells may explain some of the effects of INCS on rhinitis symptoms, but it cannot explain all of the effects because INCS also reduce the early-phase sneezing and rhinorrhea after an allergen challenge outside the pollen season. In this situation, the number of surface mast cells/basophils is very low, as it is in the absence of allergic rhinitis. The mechanism by which INCS treatment of allergic rhinitis reduces itching, sneezing, and rhinorrhea, the characteristic symptoms of an early-phase response involving mast cell release of histamine, remains to be determined. Studies should be conducted to characterize the broad range of mechanisms by which INCS produce their therapeutic effects in allergic rhinitis.
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PMID:Mode of action of intranasal corticosteroids. 1144 2

Prostaglandin (PG) D2, the major cyclooxygenase metabolite generated from immunologically stimulated mast cells, is thought to contribute to the pathogenesis of allergic diseases due to its various inflammatory effects. However, since no DP receptor antagonist has been developed as an antiallergic drug, the role of PGD2 in the pathogenesis of allergic diseases remains uncertain. Here, we report the in vivo efficacy of our newly established DP receptor antagonist, S-5751 [((Z)-7-[(1R,2R,3S,5S)-2-(5-hydroxy benzo[b]thiophen-3-ylcarbonylamino)-10-norpinan-3-yl]hept-5- enoic acid)], using various allergic inflammation guinea pig models. In allergic rhinitis models, oral administration of S-5751 dramatically inhibited not only early nasal responses, as assessed by sneezing, mucosal plasma exudation, and nasal blockage, but also late responses such as mucosal plasma exudation and eosinophil infiltration. Even when S-5751 was administered after recovery from the early responses, these late phase responses were almost completely suppressed. In addition, S-5751 alleviated allergen-induced plasma exudation in the conjunctiva in an allergic conjunctivitis model and antigen-induced eosinophil infiltration into the lung in an asthma model. These findings provide evidence for the crucial role of PGD2 as a mediator of allergic inflammation in guinea pigs and suggest that DP receptor antagonists may be useful in the treatment of allergic diseases triggered by mast cell activation.
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PMID:Prevention of allergic inflammation by a novel prostaglandin receptor antagonist, S-5751. 1145 1

Although mast cells accumulate within the mucosal epithelial layer of patients with allergic rhinitis and bronchial asthma, the responsible chemotactic factors are undefined. We investigated whether mast cells sensitized with Ag-specific IgE migrate toward the Ag. MC/9 mast cells sensitized with anti-DNP IgE migrated toward DNP-conjugated human serum albumin. This migration was directional, and the degree was stronger than that induced by stem cell factor. IL-3 and stem cell factor-dependent cultured mast cells derived from mouse bone marrow also migrated toward the Ag. Subsequent migration mediated by the Fc(epsilon)RI was significantly inhibited by incubating the cells with Y-27632, a Rho-associated coiled-coil-forming protein kinase inhibitor, or with SB203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor. Both p38 MAPK and MAPK-activated protein kinase (MAPKAPK)2 were activated following Fc(epsilon)RI aggregation, and activation of MAPKAPK2 was almost completely inhibited by 10 microM SB203580. Wortmannin or a low concentration of SB203580 partially inhibited MAPKAPK2, but did not block mast cell migration. In contrast, Y-27632 did not affect the activation of MAPKAPK2. These results indicate that Ag works not only as a stimulant for allergic mediators from IgE-sensitized mast cells, but also as a chemotactic factor for mast cells. Both p38 MAPK activation and Rho-dependent activation of Rho-associated coiled-coil-forming protein kinase may be required for Fc(epsilon)RI-mediated cell migration.
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PMID:Sensitized mast cells migrate toward the antigen: a response regulated by p38 mitogen-activated protein kinase and Rho-associated coiled-coil-forming protein kinase. 1149 18


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