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)

Calcium ions participate in the pathogenesis of asthma. Increased cytosolic concentrations of free Ca2+ must develop to trigger smooth muscle contraction, mast cell mediator release, mucous gland secretion, vagal nerve activity, and the movement of inflammatory cells into the walls of the airways. Recent interest has centered on the possibility that Ca2+ antagonists might be useful in the treatment of asthma. Evidence now exists that airway smooth muscle contraction and mast cell and basophil mediator release may be inhibited by the calcium channel blockers nifedipine and verapamil. Other experiments indicate that these drugs may interfere with EIA and bronchoconstriction provoked by cold air and methacholine, for example. CaM antagonists may also interfere with smooth muscle contraction and mediator release. It is possible that more specific calcium antagonists, both Ca2+ channel blockers and CaM-active compounds, will be developed and find use as effective antiasthmatic agents.
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PMID:Calcium antagonists and asthma. 241 Apr 77

The role of human basophils and mast cells in the pathogenesis of allergic diseases has been analyzed. Purified human basophils and mast cells release several known mediators of allergic reactions, including histamine, sulfidopeptide leukotrienes, kinin-forming enzymes, and, in the case of the mast cell, PGD2. These same mediators are released in vivo after experimental challenge in the upper airways with either allergen or cold, dry air, a stimulus used to simulate exercise-induced bronchospasm. The appearance of mast cell mediators in vivo after such challenges further implicates mast cells in the pathogenesis of allergic diseases of the airways that occur as a result of exposure to allergen or physical stimuli. During the LPR after experimental challenge of the upper airways, the pattern of mediators released (i.e., histamine, leukotrienes, and others, but no PGD2) suggests that basophils may contribute to the LPR. Antiallergic drugs that prevent mediator release in vitro, such as antihistamines, also prevent the appearance of mediators in vivo, strengthening both the validity of the in vitro test as a model of the disease and the hypothesis that mediator release is an essential element of the disease process. A model discussing the pathogenetic mechanism is presented.
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PMID:Role of human basophils and mast cells in the pathogenesis of allergic diseases. 241 Apr 78

Prostaglandin (PG) D2 and histamine concentrations have been measured in blood draining cold-challenged forearm skin in patients with cold urticaria. Local venous concentrations of both histamine and PGD2 rose in four patients who developed a whealing response. Plasma histamine concentration increased from a mean resting value of 0.24 +/- 0.09 (SD) ng/ml to peak values of 16.9 to 96.6 ng/ml. Resting concentrations of PGD2 were below the limit of detection (5 pg/ml) in three patients and 62 and 27 pg/ml in the fourth. Peak plasma PGD2 concentration after challenge ranged from 166 to 279 pg/ml. Time course of histamine and PGD2 release was similar with peak concentrations at 6 and 10 minutes, respectively. The maximum clinical response occurred between 10 and 20 minutes after challenge. Our findings demonstrate that PGD2 is produced in association with mast cell degranulation in man, but the amount, relative to histamine, is low. Despite its high potency in production of inflammatory effects, PGD2 probably has only minor direct effects in cold urticaria, although it may act to potentiate other mediators.
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PMID:Prostaglandin D2 and histamine release in cold urticaria. 242 56

Confluent spread of mature nondividing mast cells is obtained after 1 month's growth of lymph node cells taken from mice immunized with horse serum and plated on embryonic fibroblast monolayers. The degranulation capacity of these mast cells and histamine release stimulated by monoclonal IgE antibodies and their antigens were studied. The mast cells were first incubated with either anti-2,4-dinitrophenyl (DNP) IgE or with anti-ovalbumin (OVA) IgE and then with the other IgE to study the ability of one IgE specificity to saturate the receptors and block the ability of the other IgE to bind and evoke degranulation. Saturation of the receptors and maximal histamine release (86-92%) were obtained within 2-3 h incubation with excess IgE (1-10 micrograms/ml). No histamine was released after incubation for 3-4 h with the other IgE (0.38-4.0% histamine release). Seventeen days after the excess, unbound, saturating IgE anti-DNP was washed away, 75% of the histamine was still released after antigen DNP-bovine serum albumin was added. However, these mast cells were still effectively blocked from sensitization with IgE anti-OVA (1.71% histamine release). The blocking could be broken if the second IgE molecules were allowed to stay longer than 4 h in culture. From 10 h onwards, the degranulation capacity steadily increased (from 59.6% histamine release after 10 h to 79.5% after 42 h). In studies with 125I-labeled IgE, there was a direct correlation between the rate of binding of the second IgE to the mast cells (from 1.7% binding after 3 h to 75% after 48 h) and the increase in degranulation rate with the second antigen (from 2.40% histamine release to 65.4%). In contrast, only slight binding of the 125I-labeled IgE of the saturating specificity occurred (4.2% after 3 h to 12.7% binding after 48 h). Incubation of mast cells, previously saturated with 125I-labeled IgE, with cold IgE of either specificity did not proportionally reduce the cell-bound label. This suggests that no substitution of IgE molecules on the receptors occurred. When the mast cells saturated with anti-OVA were incubated with IgE anti-DNP together with tunicamycin, the development of the degranulation capacity by DNP-bovine serum albumin was inhibited. The results suggest that IgE molecules of the other specificity stimulated the appearance of new receptors on the mast cell surface.
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PMID:Degranulation of in vitro differentiated mast cells stimulated by two monoclonal IgE specificities. 243 21

Four patients with cholinergic urticaria associated with additional cardiorespiratory manifestations are described. Two patients reported cold, in addition to heat and exercise, as a factor inducing symptoms. Prospective exercise challenge documented a rise in in plasma histamine sixfold to 20-fold above baseline values that accompanied onset of symptoms. All four subjects had proved refractory to conventional antihistamine therapy. Institution of ketotifen at doses ranging from 3 to 8 mg per day resulted in symptomatic improvement, and in all four subjects a repeat exercise challenge confirmed clinical improvement. In three subjects exercise challenge with ketotifen demonstrated blockade of mast cell-mediator release. Plasma histamine levels remained at baseline. In the fourth patient, histamine rose to about half the peak observed before ketotifen therapy. These findings confirm the observation that ketotifen is both an H1 histamine-receptor antagonist as well as a stabilizer of mast cell-mediator release. We speculate that ketotifen may prove more effective than conventional antihistamines in the management of severe urticaria.
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PMID:Refractory cholinergic urticaria successfully treated with ketotifen. 237 Mar 85

Effects of zinc in gastric ulcer have been reviewed through investigations carried out on zinc acexamate (ZAC). ZAC is an organic compound that has been shown to possess an experimental antiulcer effect and a wide therapeutic index, making it a useful drug in the treatment of peptic ulcer disease. ZAC protects from ulceration in several experimental models such as pylorus occlusion, reserpine-induced ulcer, necrotizing agents, PAF-induced ulcer and cold-restraint stress. ZAC first reduces the gastric acid output by inhibiting the mast cell degranulation, an action likely to be mediated through a membrane stabilizing action. Secondly, it enhances the mucosal protection factors by increasing mucus secretion, inhibiting the H+ retrodiffusion and improving microcirculation. ZAC is also effective in acetic acid-induced chronic ulcer, restoring the continuity of the damaged mucosa. Several clinical trials have shown the usefulness of ZAC in acute and maintenance treatment of both gastric and duodenal ulcers. Endoscopic studies showed that ZAC reduced the inflammatory processes (gastritis and duodenitis) associated with ulcer healing. This reduction was statistically significant and not observed with other comparative treatments (H2-antagonists). The observed side-effects were minimal and affected less than 2% of treated patients. The pharmacological profile, clinical effectiveness and good tolerance of ZAC suggest this compound as an interesting option in the treatment of peptic disease.
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PMID:Zinc compounds, a new treatment in peptic ulcer. 266 Nov 83

The abundance of mast cells in human dermis, together with their ability to release a variety of vasoactive and pro-inflammatory mediators following cross-linkage of their cell-surface receptors for IgE, enables these cells to provide an effective defence mechanism within this organ. A similar defensive function is attributed to mast cells of other human organs such as intestine and lung which are in contact with the external environment and therefore susceptible to infiltration by foreign allergens and micro-organisms. However, mast cells of the skin apparently differ from those present in lung and intestine in being activated for histamine release by a variety of endogenous neuropeptides which stimulate the rapid release of histamine in the virtual absence of eicosanoids. This would provide a mechanism of neurogenic control of a variety of homeostatic functions such as blood flow, angiogenesis and fibroblast proliferation. Such processes would aid in the remodelling of tissue during wound healing, and increased numbers of mast cells have been noted around healing wounds of rat skin and areas of developing fibrosis. Neuropeptides modulate the activity of a variety of immuno-competent leucocytes including macrophages, monocytes and lymphocytes. The findings that skin mast cells are activated by neuropeptides suggest that these cells may also be included amongst those involved in neuro-immune interactions. Activation of skin mast cells by non-immunological stimuli may contribute to the aetiology of some forms of skin disease. Patients with chronic idiopathic urticaria appear to have enhanced vascular responsiveness to intradermal injections of the histamine liberator codeine suggesting that this disease may involve hyper-responsiveness of their mast cells to endogenous non-immunological stimuli. The findings of large increases in histamine accompanied by small increases in PGD2 in venous effluent of thermally challenged limbs of patients with cold- or heat-induced urticaria may suggest that their mast cells had been activated by a non-immunological stimulus. However, the interpretation of results gained using such relatively complex in-vivo systems are difficult, as the cellular origin of the detected mediators is by no means clear. However, it is hoped that in the future the alliance of newly developed in-vitro techniques to investigate mast cell function together with in-vivo methods to investigate their interaction with elements in their tissue environment will greatly increase our understanding of the role of the human skin mast cell in health and disease.
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PMID:The human skin mast cell. 266 2

Nine biopsy specimens from the jejunum of patients with a clinical history of food allergy and 10 from the rectal mucosa of patients with presumed 'allergic proctitis' were fixed in cold ethanol and further processed for paraffin embedding. Serial tissue sections were stained for IgE by direct (polyclonal antibody) and indirect (monoclonal antibody) immunofluorescence methods. Adjacent sections were subjected to conventional mast cell staining (astra blue). In all mucosal specimens from the jejunum and in 8 rectal ones, numerous cells were found to be positive both for astra blue by transmission microscopy and for IgE by fluorescence microscopy of the same section. With the monoclonal antibody all astra-blue-positive cells were IgE-positive; however, this was not always the case with the polyclonal reagent, probably because the fluorescence was weaker with the direct technique. Detection of IgE-positive mucosal mast cells may turn out to be of diagnostic interest in patients with adverse reactions to food.
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PMID:IgE-positive cells in human intestinal mucosa are mainly mast cells. 266 1

Cold-restraint stress produced stomach ulceration which was accompanied by a decreased glandular mucosal mast cell count and blood flow. Pretreatment with FPL55712, a leukotriene antagonist, dose-dependently prevented ulcer formation and mast cell depletion; however, it did not affect the reduced mucosal blood flow, nor did it significantly influence acid secretion and pepsin output. The role of the leukotrienes in stress ulceration is discussed in the light of the findings with FPL55712 on gastric glandular mucosal mast cell degranulation.
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PMID:The protective mechanism of FPL55712 against stress-induced gastric ulceration in rats. 273 25

In an attempt to understand the relationship between viral upper respiratory tract infection and the underlying virological and immunological mechanisms, thirty-four volunteers were inoculated intranasally with coronavirus 229E; subsequent virus shedding and/or antibody rises, indicating active infection, were observed in twenty-nine. There was a greater increase in independently measured scores of clinical severity, e.g. cold symptoms, in those with detectable IgE in nasal secretions (P less than 0.01). A similar association was found between clinical scores and serum IgE concentrations greater than or equal to 150 IU/ml, but the relationship with systemic atopy, as assessed by skin-prick tests to common allergens, was less marked. A more detailed study of twelve of the infected volunteers failed to explain these findings on the basis of mast cell mediator release, as concentrations of leukotriene B4, the sulphidopeptide leukotriene C4, and histamine, were not appreciably elevated in the nasal secretions following virus inoculation. Similarly, there was no evidence that circulating coronavirus specific IgE was produced. Thus, this study suggest that atopy may be related to the severity of cold symptoms produced by coronavirus 229E, although the exact connection has yet to be determined.
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PMID:Influence of atopy on the clinical manifestations of coronavirus infection in adult volunteers. 283 93


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