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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The screening of a rat mast cell cDNA library with a probe selected to recognize those genes preferentially or exclusively expressed by mast cells identified a rat gene sequence, RF-17, that shared homology with the beta-integrins. This integrin was expressed in rat tissues enriched for mast cells and T cells. The rat RF-17 sequence was used to isolate the murine homologue from a spleen cDNA library. The murine gene encodes a protein of 806 amino acids that is the probable homologue to the human beta 7 chain. Transcripts specific for the murine gene are found in the thymus, spleen, and lung. To attempt to identify the gene product for this new integrin chain, we examined the murine T cell line TK-1, which expresses a novel integrin heterodimer, lymphocyte Peyer's patch high endothelial venule adhesion molecule (LPAM-1), of a known alpha 4 chain and an unknown beta P chain, for expression of murine beta 7 (RF-17). This cell line expresses high levels of RF-17 transcripts, suggesting that beta P is encoded by the beta 7 gene. Bone marrow cells induced to differentiate into mast cells via IL-3 express the beta 7 gene as well as the genes encoding the murine integrin alpha 4 and beta 1 proteins. Surface staining analysis indicates that these cells express an alpha 4-containing integrin complex throughout the differentiation process. These data suggest that the Peyer's patch homing LPAM-1 receptor expressed by a subset of T cells consists of the beta 7 gene product and the alpha 4 chain, and that this integrin chain complex is also found on the surface of maturing mast cells. The presence of beta 1 transcripts also suggests that these maturing mast cells possess the LPAM-2 integrin complex (alpha 4/beta 1) as well. The experimental strategy described in this manuscript has, thus, identified a novel murine beta-integrin chain that is expressed by rodent T cells and mast cells.
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PMID:Expression of murine beta 7, alpha 4, and beta 1 integrin genes by rodent mast cells. 138 90

Previously we have reported that rodent mast cells synthesize the mRNA encoding the alpha and beta integrin chains (alpha 4, beta 1 and beta 7) of the lymphocyte Peyer's patch adhesion molecule (LPAM)-1 and LPAM-2 lymphocyte homing receptors, and that they possess an alpha 4-containing integrin complex on their cell surface. In this report, we have examined the expression of these integrin chain genes by mature connective tissue mast cells (CTMC) and by bone marrow-derived mast cells (BMMC) differentiated from bone marrow precursor cells in the presence of interleukin (IL)-3 and/or the c-kit ligand (also known as mast cell growth factor and stem cell growth factor). High levels of both the beta 7 and beta 1 transcripts were present in mature CTMC while those encoding the alpha 4 chain were absent. Similarly, when BMMC were grown in IL-3 for 28 days and analyzed for integrin chain transcripts, those specific for the alpha 4 chain were also diminished compared to beta 7 and beta 1 transcripts. To compare the expression of these integrin genes during mucosal mast cell and CTMC development, BMMC were derived in the presence of IL-3 alone, c-kit alone, or IL-3/c-kit together. These experiments indicated that c-kit inhibited the transcription of the beta 7 and Fc epsilon RI genes while enhancing alpha 4 transcript levels. The enhancement of alpha 4 levels, however, was abrogated with the addition of IL-3. Similarly, the c-kit-induced depression of beta 7 and Fc epsilon RI transcript levels was overcome by the addition of IL-3. These data suggest that the integrin complexes synthesized by the mast cells may differ depending upon their path of differentiation and that another alpha chain integrin may be synthesized to complex with the beta 7 and/or beta 1 chains.
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PMID:Modulation of integrin expression during mast cell differentiation. 138 93

The delayed-type hypersensitivity reaction (DHR) in human skin is prototypic for many inflammatory dermatoses. However the cellular events that precede gross lesion formation are unknown. In this study, inflammatory cell populations and adhesion molecule expression in early phases of DHR elicited by 2,4-dinitrochlorobenzene were evaluated. The first discernible event (at 1 hour) was mast cell degranulation, followed by induction of endothelial leukocyte adhesion molecule (ELAM-1) expression on dermal postcapillary venules at 2 hours. Endothelial leukocyte adhesion molecule expression peaked at 24 hours and declined by 48 hours. In contrast, endothelial expression of intercellular adhesion molecule-1 (ICAM-1) remained at constitutive levels. Intrafollicular T-cell migration occurred independent of ICAM-1 expression and commenced as early as 4 hours after challenge. Mature, activated CD4-positive lymphocytes that expressed a helper-inducer/memory phenotype predominated in early lesions. These results demonstrate in vivo that mast cell degranulation, ELAM-1 expression, and memory T-cell-follicular interactions are key events in subclinical evolutionary stages of cutaneous DHR.
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PMID:Early cellular events in evolving cutaneous delayed hypersensitivity in humans. 170 93

Oral lichen planus (LP) is a common mucosal disorder in which cell mediated immunity is thought to play a major role. In this paper, a unifying hypothesis which attempts to integrate cellular and molecular signals in the local immune response in oral LP is presented. In this model, modified keratinocyte surface antigens are the target for the cytotoxic cell response which characterizes oral LP, whereas mast cells and antigen presenting Langerhans cells are key cellular elements in the evolving lesion. It has been established that mast cell degranulation induces adhesion molecule expression on endothelium which facilitates lymphocyte homing to the tissues. These adhesive interactions between lymphocytes and keratinocytes are postulated to be important determinants in the effector phase of the lesion. Cytokines produced by both lymphocytes and keratinocytes which influence the local immune response could promote chronicity. Accordingly, modulation of immunologic events is a potential therapeutic approach for oral LP.
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PMID:Immunopathogenesis of oral lichen planus. 226 34

Allergic rhinitis is the sixth most prevalent chronic health condition in the United States. To study the pathogenesis of the allergic response, we have used a model of nasal provocation with antigen. During the initial reaction of an allergic subject to allergen provocation, increases occur in the levels of histamine, tryptase, and prostaglandin D2. This pattern of mediator release, combined with histologic evidence of mast-cell degranulation, strongly supports the role of the mast cell in the acute allergic reaction. The response to antigen, however, does not end with mast-cell degranulation. Hours after challenge we observed the spontaneous recurrence of symptoms and increased responsiveness to antigenic and nonantigenic stimuli. Our central hypothesis is that cellular infiltration and activation after antigen challenge are responsible for the observed increase in nasal reactivity. The predominant cells in nasal lavage 24 hours after challenge are eosinophils and neutrophils, whereas the predominant cell in the mucosa is the CD4+ lymphocyte. An early step in the movement of cells from the peripheral blood involves adhesion between circulating leukocytes and the endothelium. Evidence suggests that vascular endothelial adhesion molecule may be responsible in part for the selective adherence of eosinophils to the endothelium.
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PMID:Observations on the response of the nasal mucosa to allergens. 752 55

Mast cells are granule-containing secretory cells which are distributed preferentially about the microvascular bed in oral mucosa. This work examined the contribution of mast cell mediators to inflammation in the oral cavity. Mast cells in oral tissues expressed the serine proteases, tryptase and chymase, with a minor subpopulation being chymase-negative. Mast cells contained the cytokine tumour necrosis factor-alpha (TNF) in their granules. Degranulation of mast cells was a consistent feature of inflammatory lesions (lichen planus, gingivitis, pulpitis, periapical inflammation). In lichen planus, intracellular stores of TNF were depleted, and expression of mRNA for TNF was upregulated, indicating ongoing production and release of the cytokine. The density of mast cells in tissue compartments was related to the level of expression of E-selectin, an endothelial adhesion molecule which is known to be induced in skin by TNF derived from degranulating mast cells. Further attention should be directed toward the role of mast cell products, particularly TNF, in inflammation in the oral cavity.
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PMID:Relationship between mast cell degranulation and inflammation in the oral cavity. 756 63

Fluticasone propionate (FP) is a novel androstane glucocorticoid with potent anti-inflammatory activity which has been effectively used, intranasally, as therapy for seasonal and allergic perennial rhinitis. When taken by the inhaled route, FP has shown significant therapeutic efficacy in the management of asthma. Fluticasone propionate is a highly lipophilic molecule with good uptake, binding and retention characteristics in human lung tissue. Fluticasone propionate has high glucocorticoid receptor selectivity and affinity, demonstrating rapid receptor association and slow receptor dissociation. In vitro, FP has been shown to potently inhibit T lymphocyte proliferation, cytokine generation, tumour necrosis factor alpha (TNF-alpha)-induced adhesion molecule expression, interleukin-5-induced eosinophilia, mucosal oedema and toluene 2,4-diisocyanate-induced mast cell proliferation, while promoting secretory leucocyte protease inhibitor production and eosinophil apoptosis. In human studies, FP has demonstrated marked vasoconstrictor potency in normal subjects and inhibited antigen-induced mucosal platelet activating factor/eicosanoid production, T lymphocytes and CD25+ cells in patients with rhinitis. Biopsy data from mild asthmatics demonstrate FP-associated reduction in CD3, CD4, CD8 and CD25 cells, with an accompanying reduction in eosinophil and mast cell markers. Clinical studies have evaluated lung function, bronchial reactivity, exacerbation rates and oral corticosteroid-sparing effect. Results show that FP has at least twice the clinical potency of beclomethasone dipropionate and budesonide. This appears to be achieved without an accompanying increase in systemic effects, suggesting a therapeutic index which may be higher than other currently available inhaled corticosteroids.
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PMID:Fluticasone propionate--an update on preclinical and clinical experience. 756 73

The recently cloned interleukin 13 (IL-13) shares most investigated biological activities on B lymphocytes and monocytes with IL-4. In this study we investigated the potential role of IL-13 in regulating human mast cell activities. The effects of IL-13 on the expression of an immediate-early response gene (c-fos), proliferation, expression of mast cell-associated cell surface antigen (CD54 and Kit), and in vitro differentiation of human mast cells, were investigated. We compared the effect of IL-13 with that of IL-4. Both IL-13 and IL-4 induced expression of c-fos in cells from the human mast cell line HMC-1. This indicates that mast cells express functional receptors for IL-13. IL-13 and IL-4 decreased the proliferation rate of HMC-1 cells. However, IL-13 was less potent than IL-4. Human mast cells constitutively express the adhesion molecule ICAM-1 (CD54) and the receptor for stem cell factor (Kit) (CD117). The expression of CD54 was increased after treatment with IL-13 or IL-4, whereas the expression of Kit was decreased. Also in this action IL-4 was more potent than IL-13. By culturing mononuclear cells from cord blood in the presence of stem cell factor there is a differentiation of tryptase-positive mast cells in the cultures. This process was inhibited when IL-4 was present. In contrast, IL-13 did not affect the expression of tryptase during differentiation of stem cell factor dependent cord blood-derived mast cells. Taken together, these findings indicate that IL-13 has regulatory effects on human mast cells. The effect overlaps with but is also different from that of IL-4.
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PMID:Effects of interleukin (IL)-13 on immediate-early response gene expression, phenotype and differentiation of human mast cells. Comparison with IL-4. 770 21

Cytokines are proinflammatory protein mediators produced by many cells, including mast cells, T lymphocytes, eosinophils, airway epithelial cells, and macrophages. There are numerous in vitro and in vivo animal and human studies showing that cytokines are released as a result of allergic reactions. Cytokines mediate allergic inflammation by activating eosinophils, promoting mast cell development, regulating immunoglobulin isotype switching to immunoglobulin E, modulating adhesion molecule regulation, and promoting both neutrophil and eosinophil chemotaxis. Furthermore, there are data that show the pro-inflammatory effects of cytokines may be blocked by cytokine antagonists. This report reviews the in vitro and in vivo animal and human studies of allergic models of cytokine production and regulation. It also discusses the specific roles of cytokines in the allergic inflammatory response and asthma.
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PMID:Allergic models and cytokines. 795 97

Nitric oxide (NO) synthesis inhibition causes neutrophil adhesion to endothelium via a mast cell- and oxidant-dependent mechanism. The objective of this study was to delineate the cascade of events in the mast cell- and oxidant-induced neutrophil-endothelium interactions after NO synthesis inhibition. Mast cells were isolated and purified from the rat peritoneal cavity and coadministered with neutrophils to wells of endothelium. This system was treated with an NO synthesis inhibitor (NG-nitro-L-arginine methyl ester; L-NAME) for 60 minutes. L-NAME did not induce neutrophil-endothelium interactions in the absence of mast cells, but the addition of mast cells in a ratio as low as 1:50 mast cells to neutrophils was sufficient to induce a large increase in neutrophil adhesion to endothelium within 20 to 25 minutes. L-arginine, NO donors, and 8-bromo-cGMP reversed the L-NAME effect, whereas NG-nitro-D-arginine methyl ester alone had no proadhesive effect. The adhesion was inhibited by an anti-CD18 or an anti-intracellular adhesion molecule-1 antibody and a platelet-activating factor-receptor antagonist. Inhibition of NO in isolated endothelial monolayers induced oxidant release (reduction of cytochrome C) into extracellular fluid. The endothelium-derived superoxide contributed to the mast cell-induced adhesion, inasmuch as the extracellular antioxidant superoxide dismutase reduced the neutrophil adhesion response as did disruption of endothelial function. There was some direct activation of mast cells with L-NAME (independent of endothelium) inasmuch as intracellular calcium and oxidative stress increased within mast cells after L-NAME treatment, and this translated into increased neutrophil adhesion to nonendothelial substrata. These data demonstrate that depletion of NO increases oxidative stress within mast cells and endothelium and together these events promote neutrophil adhesion within the vasculature.
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PMID:A balance between nitric oxide and oxidants regulates mast cell-dependent neutrophil-endothelial cell interactions. 888 91


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