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)

Aspirin therapy for patients with systemic mast cell disease (SMCD) decreases the production of prostaglandin D2, which is thought to be a major mediator of flushing. Paradoxically, in 5 to 10% of patients with SMCD, administration of aspirin causes massive mediator release and an anaphylactoid reaction. We attempted aspirin desensitization in a 34-year-old man with SMCD (confirmed by bone marrow biopsy) who was incapacitated by severe flushing episodes and hypotension. His baseline mediator levels of plasma calcitonin, urinary histamine, and urinary N-methyl-imidazoleacetic acid were abnormal. Pentagastrin stimulation increased the plasma level of calcitonin from 47 pg/mL to 130 pg/mL (normal, less than or equal to 110) at 5 minutes. Oral aspirin desensitization was begun; however, after a cumulative dose of 620 mg, an anaphylactoid reaction ensued in conjunction with hypotension, abdominal cramping, and flushing. Coincidentally, 1 hour after the episode, the plasma calcitonin level increased from 37 pg/mL to 540 pg/mL, and the serum tryptase level increased from 1 ng/mL to 3.9 ng/mL. Six hours after the episode, the urine level of histamine increased from 90 micrograms/g creatinine to 337 micrograms/g creatinine, and the urinary N-methylimidazoleacetic acid increased from 32 mg/24 h to 81 mg/24 h. Hence, the patient had increased basal levels of plasma calcitonin that increased substantially during aspirin desensitization and increased to above the upper limit of normal during pentagastrin stimulation. Human mast cells may be capable of producing calcitonin or causing secretion of calcitonin in response to skeletal changes.
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PMID:Increased plasma calcitonin levels in systemic mast cell disease. 793 97

We measured serial serum tryptase levels in a case of intraoperative anaphylaxis caused by allergy to latex. The serum tryptase level was elevated 7 hours after the hypotensive episode and returned to normal after recovery 4 months later. Both skin tests to latex and serum IgE to latex confirmed latex allergy in this patient. To our knowledge, this is the first report of an elevated serum tryptase level in intraoperative anaphylaxis caused by latex allergy. This observation confirms the role of mast cell degranulation in anaphylaxis caused by allergy to latex.
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PMID:Elevated serum tryptase level in a case of intraoperative anaphylaxis caused by latex allergy. 794 46

Anaphylaxis is a life-threatening disease that characteristically presents with multiple arrays of dermatologic, respiratory, cardiovascular, and gastrointestinal derangements, in general, suddenly after exposure to an allergen. It can, however, occur without an identifiable precipitant or event, and this well-defined entity has been called idiopathic anaphylaxis. The diagnosis of idiopathic anaphylaxis is made after an appropriate allergic evaluation and exclusion of a provocative trigger. We report an unusual case of manifesting with gastroenteritis, urticaria, hypotension, and syncope. Measurement of serum tryptase, a mast cell enzyme, was used to substantiate the diagnosis. Tryptase level is a useful test that can be used to help diagnose this potentially fatal disease.
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PMID:Serum tryptase in idiopathic anaphylaxis: a case report and review of the literature. 801 May 39

The mechanism of water-induced pruritus in patients with polycythemia vera is unknown. Evidence has been presented previously that bathing or showering may trigger mast cell degranulation and that release of a mediator by mast cells may be responsible for the pruritus. Tryptase is a specific marker of human mast cell secretory granules and its presence in body fluids indicates mast cell degranulation. In this study, serum tryptase levels were measured both before and one hour after showering in 11 patients suffering from polycythemia vera and water-induced pruritus. Tryptase was not found in the serum of any of the subjects one hour after showering, when levels would be expected to be near peak had significant mast cell degranulation occurred. These results argue against mass cell degranulation with systemic release of a mast cell product as the mechanism for water-induced pruritus in patients with polycythemia vera.
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PMID:Polycythemia vera and water-induced pruritus: evidence against mast cell involvement. 816 24

In order to examine the hypothesis that in aspirin-induced asthma (AIA) cyclooxygenase inhibition is associated with enhanced release of leukotrienes (LTs), we measured urinary leukotriene E4 (LTE4) and 11-dehydro-thromboxane B2 (TXB2) (as a measure of cyclooxygenase production) following challenge with oral aspirin or inhaled methacholine, in 10 AIA patients. We also determined serum tryptase and eosinophilic catonic protein (ECP) levels, in order to evaluate mast cell and eosinophil activation. Urinary LTE4 excretion was increased sevenfold 4-6 h after aspirin challenge, while 11-dehydro-TXB2 decreased gradually reaching 50% baseline levels 24 h after challenge (p < 0.05). This was accompanied by a significant fall in blood eosinophil count at 6 h, and a tendency to a rise in ECP. The intensity of both LTE4 and 11-dehydro-TXB2 responses depended on the dose of aspirin used (p < 0.001, analysis of variance (ANOVA)). The accompanying maximum fall in forced expiratory volume in one second (FEV1) was not correlated with peak LTE4 levels. In contrast to aspirin, methacholine challenge producing comparable bronchial obstruction, did not alter eicosanoid excretion or serum tryptase or ECP levels. In a separate study, lysine-aspirin inhalation challenge was performed in seven AIA patients, four of whom had responded with a rise in serum tryptase to oral aspirin challenge. Challenge with inhaled aspirin led to similar bronchoconstriction as with oral challenge, but non-respiratory symptoms such as scarlet flush or rhinorrhea were absent, and serum tryptase levels remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cysteinyl leukotrienes overproduction and mast cell activation in aspirin-provoked bronchospasm in asthma. 838 6

Tryptase is a mast cell-specific marker of degranulation. To investigate the possible diagnostic value of tryptase in allergic rhinitis, we measured the levels in both serum and native nasal fluid with a sandwich RIA-assay (Pharmacia). Twenty-three allergic patients and five patients with chronic ethmoidal sinusitis were included. Eighteen of the 23 allergic patients were tested within the pollen season or had perennial rhinitis; the remainder were tested at least 1 month out of the pollen season. None of the patients had detectable serum tryptase (> 0.1 ng/ml). Also patients with chronic ethmoidal sinusitis showed no tryptase in nasal fluid. One of seven allergic patients tested out of season had slightly increased nasal tryptase of 1.8 ng/ml. In patients with active nasal allergy, the tryptase in nasal fluid ranged from 6.4 ng/ml to 640 ng/ml with a mean of 101 ng/ml and SD 173. These results show a clear distinction between active and non-active nasal allergy and other non-mast-cell-related nasal disease. Further, nasal tryptase release by natural allergen exposure is even higher than that observed in allergen challenge tests.
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PMID:Tryptase in nasal fluid is a useful marker of allergic rhinitis. 845 35

The inflammatory mediators of allergy were investigated in symptomatic patients suffering from upper respiratory tract allergy. The serum tryptase level as an indicator of mast cell activation and serum eosinophil cationic protein level as an indicator of eosinophil activation were measured. They did not find any alteration in the serum level of tryptase. The level of eosinophil cationic protein significantly increased in symptomatic patients comparing to normal healthy controls. There was not any correlation to the severity of symptoms and to the absolute eosinophil count in the peripheral blood. The different activation possibilities of the eosinophil granulocytes are discussed, highlighting the role of Th2-helper lymphocytes.
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PMID:[Allergic inflammatory markers in upper respiratory allergies]. 846 28

Allergic asthmatic patients were challenged with specific allergen that resulted in early asthmatic reaction (EAR). Serum tryptase concentration (STC) and neutrophil chemotactic activity (NCA) were measured before and during EAR. A significant increase in neutrophil chemotactic activity was noticed in the 60th min, without an accompanying increase in serum tryptase concentration. The rise in neutrophil chemotactic activity in our study confirms previous observations in this field. However, because of the numerous cellular sources for neutrophil chemotactic activity, it does not seem to be a gold standard for measurement of mast cell activation. Undetectable levels of serum tryptase concentration during EAR in our study do not exclude the role of the mast cell in its pathogenesis. To our knowledge, only massive mast cell degranulation is reflected in the circulation as an increased tryptase concentration. In the case of upper respiratory allergic reactions, mast cell degranulation definitely takes place, but does not result in evident changes in serum tryptase concentration. We conclude that mast cell activation during allergen-induced EAR is poorly represented in the circulation.
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PMID:Is mast cell activation during asthmatic reaction reflected in the circulation? 865 23

Tryptase is a serine protease secreted by mast cells that is able to activate other cells. In the present studies we have tested whether these responses could be mediated by thrombin receptors or PAR-2, two G-protein-coupled receptors that are activated by proteolysis. When added to a peptide corresponding to the N terminus of PAR-2, tryptase cleaved the peptide at the activating site, but at higher concentrations it also cleaved downstream, as did trypsin, a known activator of PAR-2. Thrombin, factor Xa, plasmin, urokinase, plasma kallikrein, and tissue kallikrein had no effect. Tryptase also cleaved the analogous thrombin receptor peptide at the activating site but less efficiently. When added to COS-1 cells expressing either receptor, tryptase stimulated phosphoinositide hydrolysis. With PAR-2, this response was half-maximal at 1 nM tryptase and could be inhibited by the tryptase inhibitor, APC366, or by antibodies to tryptase and PAR-2. When added to human endothelial cells, which normally express PAR-2 and thrombin receptors, or keratinocytes, which express only PAR-2, tryptase caused an increase in cytosolic Ca2+. However, when added to platelets or CHRF-288 cells, which express thrombin receptors but not PAR-2, tryptase caused neither aggregation nor increased Ca2+. These results show that 1) tryptase has the potential to activate both PAR-2 and thrombin receptors; 2) for PAR-2, this potential is realized, although cleavage at secondary sites may limit activation, particularly at higher tryptase concentrations; and 3) in contrast, although tryptase clearly activates thrombin receptors in COS-1 cells, it does not appear to cleave endogenous thrombin receptors in platelets or CHRF-288 cells. These distinctions correlate with the observed differences in the rate of cleavage of the PAR-2 and thrombin receptor peptides by tryptase. Tryptase is the first protease other than trypsin that has been shown to activate human PAR-2. Its presence within mast cell granules places it in tissues where PAR-2 is expressed but trypsin is unlikely to reach.
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PMID:Interactions of mast cell tryptase with thrombin receptors and PAR-2. 902 Jan 12

Six patients with documented systemic mast cell disease were enrolled in a 1-year, phase I study to determine the possible benefits of interferon alpha-2b (IFN-alpha). IFN-alpha therapy was begun at a dosage of 0.5 million units/day (MU/day) by subcutaneous injection and increased, as tolerated, to 3.0 MU/day. Subsequent dose modifications were made based on clinical tolerance and response. No immediate, adverse reactions to IFN-alpha occurred. Several patients showed symptomatic improvement. In two patients ascites resolved and did not recur. Two other patients reported improved energy levels and had decreased size of retroperitoneal, measenteric and retrocrural nodes. One patient failed to benefit and died shortly after completing 12 months of therapy. Bone marrow mastocytosis decreased by 5% to 10% after 12 months of therapy with IFN-alpha. Although five of the six patients had a decrease in the urinary excretion of 1-methyl-4-imidazole acetic acid, serum tryptase values did not appreciably change in any patient. Side-effects from IFN-alpha included hypothyroidism, thrombocytopenia and depression. It is concluded that although treatment with IFN-alpha was associated with a decline in bone marrow mastocytosis and reduced excretion of histamine metabolites, prolonged therapy may be needed and dose-limiting side-effects are frequent.
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PMID:Response of severe systemic mastocytosis to interferon alpha. 958 Aug 6


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