Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immediate, type 1 allergic reactions occur following interaction between allergen, immunoglobulin E (IgE), and the mast cell or basophil. Allergen-induced activation of these cells leads to the release of a number of mediators that are responsible for the symptoms observed during an allergic reaction. Recent progress in elucidating the structures, and in developing syntheses for platelet aggregating factor and the leukotrienes, promises to increase our understanding of the immunopharmacology of allergic and inflammatory reactions. The need for the standardization of allergen extracts is emphasized, and current activity in this area is highlighted.
 ...
PMID:Allergy, allergens and allergen standardization. 648 86

With the ever-increasing use of pharmaceuticals and the relatively high risk of developing drug allergies, particularly for patients in hospitals and for ambulatory patients with a history of drug allergy, the need to develop in vitro assays for drug allergy is great. In the early 1970's a mast cell technique was developed for diagnosis of drug allergies. A PRIST inhibition assay has also recently been developed to detect IgE antibodies to drug allergens. This test has also been referred to as the Total IgE Inhibition Test by Specific Drug Allergen, and is a variant of the in vitro RAST Test. In vitro mast cell and IgE inhibition tests are applied for identification of drug and chemical allergens and for their cautious clinical trial to prevent future drug and chemical reactions. Over the last eight years, over 1,300 patients were examined utilizing the mast cell technique. Over 100 drugs were tested, with penicillin, barbiturates, "caine" derivatives and sulfonamides most frequently employed. Of 270 patients with well-defined drug reactions, 190 (70 per cent) gave a positive response to the mast cell test. Eighty-five per cent of sera tested with Type I reactions gave a mast cell response. Of these, a group of 30 patients was studied with PRIST inhibition as well. Procedures for comparative testing of necessary drugs and/or chemicals in cases of high anaphylaxis risk of reaction in the clinical setting, hospital or office are included in the study as well as individual case reports. Mast cell assay coupled with IgE inhibition has been successfully used to diagnose drug and chemical allergic reactions. The incidence of positivity is high when the offending drug causes a Type I allergic reaction. The cases reported indicate that both the Mast Cell and the PRIST inhibition assays are useful for diagnosing and setting the clinical treatment and clinical course of the patient. The mast cell assay would be potentially employed for patient use in hospitals where the incidence of drug allergy is highest and for occupational health in the chemical industry. The greatest potential would be in outpatient care applied to patients with multiple drug allergies in the selection of safe drugs (test negative by both methods, and other clinical studies) for future drug usage.
 ...
PMID:The diagnosis of drug allergies. Utilizing in vitro mast cell test and IgE inhibition test. 681 53

The clinical symptoms of allergy are caused by cellular (IgE-triggered) responses to an allergen. Effector cells of allergy include eosinophil and basophil granulocytes, as well as tissue mast cells. Growth and accumulation, as well as IgE-dependent and independent functions of these cells are regulated by distinct proteohormones and peptides. The hemopoietic cytokines IL-3 (interleukin-3), IL-5 and GM-CSF (granulocyte-macrophage colony-stimulating factor) are involved in the regulation of basophils (and eosinophils), whereas the ligand for c-kit, SCF (stem cell factor) is a mast cell-specific agonist. Basophils and mast cells express high-affinity IgE-binding sites. Allergen binding to IgE on mast cells and basophils, and consecutive cross-linking of IgE receptors is followed by production and/or secretion of inflammatory mediator substances. Specific activation and deactivation of mast cells/basophils in vitro has been demonstrated by use of recombinant cytokines and allergens, and specific haptens or by use of novel drugs, and should lead to epitope-specific diagnosis and better management of allergic diseases in the future.
 ...
PMID:[Effector cells in allergy: biological principles and new pharmacologic concepts]. 750 62

Allergen injection immunotherapy in selected patients is effective and has wide ranging anti-inflammatory effects. These include modulation of serum (and presumably local) IgE and IgG antibody responses, a reduction in mast cell numbers in the target organ and inhibition of mast cell mediator release. Tissue eosinophilia and eosinophil activation are also reduced. We have compared and contrasted the effects of immunotherapy and topical corticosteroids on allergen-induced late nasal responses. Both treatments inhibit allergen-induced late nasal symptoms and associated CD4+ T cell and eosinophil recruitment, possibly by distinct mechanisms. Whereas topical corticosteroids may act by suppressing cytokine mRNA expression for Th2-type cytokines, particularly interleukin-4, immunotherapy induces a local Th1 response with an increase in interferon-gamma.
 ...
PMID:Changes in allergic inflammation associated with successful immunotherapy. 761 51

Improved treatment approaches for seasonal allergic rhinitis are based on the increasing knowledge about allergic inflammation and on the improved efficacy of newer drugs. The current management concept includes an individualised composition of the different approaches including allergen avoidance, topical treatment and the use of systemic drugs and specific immunotherapy. Allergen avoidance, supported by pollen information, leads to a remarkable reduction of daily challenge situations. There is an increasing trend towards topical use of corticosteroids (e.g. budesonide and fluticasone) and mast cell stabilisers [e.g. sodium cromoglycate (cromolyn sodium), nedocromil and isospaglumic acid (N-acetylaspartylglutamic acid)] because of the potency of these drugs to impair the destructive activity of allergic inflammation. Potent histamine H1-receptor antagonists (e.g. azelastine and levocabastine) are approved for local treatment and lead to prompt relief of troublesome symptoms. A new generation of orally active antihistamines (e.g. astemizole, cetirizine, loratadine and terfenadine) have tended to be called 'antiallergics' because of activity other than H1-blockade. Furthermore, these newer compounds are less likely to cause sedation. Immunotherapy is still an integrated component in the treatment strategy. Standardised allergen extracts of high quality raise the treatment efficacy and safety. Overall, forming an individual combination of treatment approaches gives the best result.
 ...
PMID:Seasonal allergic rhinitis. Newer treatment approaches. 768 72

Allergen-induced bronchoconstriction involves mast cell activation. Tryptase is a mast cell serine protease that is released during this process, but little is known about the action of tryptase in the airway. The purpose of this study was to determine: (1) if aerosolized tryptase causes bronchoconstriction, and (2) the mechanism by which this occurs. We measured mean pulmonary flow resistance (RL) in five allergic sheep before and after consecutive inhalations of 100 and 500 ng tryptase (in 2 ml total volume). Inhaled tryptase at 100 and 500 ng increased RL (mean +/- SE) by 33 +/- 12 and 122 +/- 8% (p < 0.05) over baseline. The response was reproducible upon repeat challenges. These studies were repeated in the same animals after pretreatment with aerosolized APC 366 (9 mg/3 ml), a specific tryptase inhibitor. In APC-366-treated sheep, tryptase increased RL by 10 +/- 3 and 6 +/- 2% (p < 0.05 versus control values) at 100 and 500 ng, respectively. The response to tryptase was also blocked by pretreating the sheep intravenously with the histamine H1-antagonist chlorpheniramine (2 mg/kg), in which RL increased only 5 +/- 4 and 7 +/- 6% after 100 and 500 ng tryptase. APC 366, however, did not block histamine-induced bronchoconstriction. Consistent with these findings was the observation that segmental bronchial challenge with tryptase (1 microgram) resulted in a significant increase in histamine levels in bronchoalveolar lavage. Inhaled tryptase (500 ng) also caused airway hyperresponsiveness to aerosolized carbachol 2 h after tryptase challenge. This tryptase-induced airway hyperresponsiveness could be blocked either by pretreating the sheep with APC 366 (30 min before challenge) or by treating the sheep 30 min after challenge. These results indicate that inhaled tryptase causes bronchoconstriction and airway hyperresponsiveness in allergic sheep by an event that may involve mast cell activation.
 ...
PMID:Inhaled tryptase causes bronchoconstriction in sheep via histamine release. 881 Jun

Allergic rhinitis is an increasing problem for which new and exciting therapies are being developed. These can be understood through an appreciation of the newer concepts of pathogenesis of allergic rhinitis. Allergen induces Th2 lymphocyte proliferation in persons with allergies with the release of their characteristic combination of cytokines including IL-3, IL-4, IL-5, IL-9, IL-10, and IL-13. These substances promote IgE and mast cell production. Mucosal mast cells that produce IL-4, IL-5, IL-6, and tryptase proliferate in the allergic epithelium. Inflammatory mediators and cytokines upregulate endothelial cell adhesion markers, such as vascular cell adhesion molecule-1. Chemoattractants, including eotaxin, IL-5, and RANTES, lead to characteristic infiltration by eosinophils, basophils, Th2 lymphocytes, and mast cells in chronic allergic rhinitis. As our understanding of the basic pathophysiologic features of allergic rhinitis continues to increase, the development of new diagnostic and treatment strategies may allow more effective modulation of the immune system, the atopic disease process, and the associated morbidity.
 ...
PMID:Pathogenesis of allergic rhinitis. 904 69

The identity of the histamine-potentiating activity detected in the rat anaphylactic pleural washing was investigated. Wistar rats of both sexes, weighing 150-200 g, were sensitized by injecting subcutaneously (sc) a mixture of ovalbumin and Al(OH)3 14 days before allergen challenge. In sensitized rats, intrapleural (ipl) injection of ovalbumin (12 micrograms/cavity) caused an intense protein exudation. A single ipl administration of compound 48/80 (12 micrograms/cavity) exhausted the resident mast cell population and turned the pleural cavity hyporeactive to the allergen challenge performed 5 days later. Allergen-induced exudation occurred in parallel to a dramatic decrease in the amount of cell-stored histamine (from 9.6 +/- 1.4 (N = 8) to 1.3 +/- 0.1 (N = 6) micrograms/cavity, P < 0.001) in the pleural fluid within 10 min. The anaphylactic cell-free pleural washing obtained at this time, as well as histamine at a concentration equivalent to that stored in pleural mast cells (10 micrograms/cavity), did not induce pleural exudation when injected into normal rats. In contrast, the combined administration of histamine and anaphylactic pleural washing led to remarkable pleural exudation, comparable to that obtained with a high dose of histamine (200 micrograms/cavity) alone. It is noteworthy that the anaphylactic washing from compound 48/80-pretreated rats failed to synergize with histamine. Also, synergism was not reproduced when recipient rats were pretreated with methysergide (50 micrograms/cavity). Consistently, serotonin (5 micrograms/cavity) acted synergistically with histamine (10 micrograms/cavity), producing a greater exudative response than observed with the sum of the effects of each vasoactive amine alone. The results indicate that serotonin accounts for the histamine-potentiating activity noted in the anaphylactic pleural washing, confirming that the synergistic interaction between these vasoactive amines plays a critical role in the rat allergic pleurisy.
 ...
PMID:Histamine-potentiating activity in rat anaphylactic pleural fluid: role of serotonin. 918 Oct 89

Mast cells and basophils are metachromatic cells that participate in allergic inflammation. Allergen challenge to the airways of atopic asthmatic individuals increases levels of metachromatic cells, which may reflect an increase in mast cells, basophils, or both. We conducted a study to characterize the kinetics of basophil and mast cell recruitment to the airways of atopic asthmatic subjects after allergen inhalation challenge, using monoclonal antibodies specific for each type of cell. Of 19 subjects, 14 developed both early- and late-phase asthmatic responses (dual responders [DRs]), whereas five developed only early asthmatic responses (early responders [ERs]) after allergen inhalation. There was a significant increase in the number of sputum eosinophils (p < 0.002) and basophils (p < 0.002) at 7 h and 24 h after challenge in both ERs and DRs. There was also a significant increase in the number of activated eosinophils (p = 0. 00002) and mast cells (p = 0.009) in sputum at 7 h and 24 h after challenge in DRs, but not in ERs (p > 0.4). DRs had a significantly higher number of allergen-induced sputum basophils than did ERs (p < 0.01), and sputum basophils correlated significantly with airway hyperresponsiveness (AHR) to methacholine at 24 h after challenge (r = 0.66, p = 0.002). DRs tended to have higher allergen-induced basophil levels than did ERs, which may contribute to the observed AHR.
 ...
PMID:Increased numbers of both airway basophils and mast cells in sputum after allergen inhalation challenge of atopic asthmatics. 1080 41

In the context of IgE/allergen interactions, affinity is largely determined by the stability of the allergen-IgE complex: a low affinity is usually equated with a rapid dissociation of the complex. Regular solid-phase assays are not well suited for affinity estimates because of multivalency effects, "unstirred layer" effects and "invisible" antibodies. Elution of IgE bound to solid-phase coupled allergen might be a good measure of intrinsic affinity, provided that reassociation of antibodies is prevented by a high concentration of soluble allergen. Allergen-mediated IgE-dependent triggering of a mast cell is presumably a two-step process. During the first step, the allergen is bound to a cell-bound IgE antibody and dragged over the cell surface. The second step is the interaction between this cell-bound allergen and another IgE antibody. The hypothesis is that the affinity requirements for the first step are higher than for the second. The implication is that a mast cell can be triggered by a single high-affinity antibody in combination with one or more low-affinity antibodies.
 ...
PMID:Structural aspects of cross-reactivity and its relation to antibody affinity. 1129 3


<< Previous 1 2 3 4 5 6 Next >>