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)

Exercise-induced asthma (EIA) may affect up to 90% of patients with asthma. Hyperpnea associated with exercise leads to increased airway water and heat loss, which contributes to the development of EIA. Measurement of circulating mediators has suggested that mast cells may participate in the development of EIA via release of histamine and neutrophil chemotactic factor. To evaluate further the contribution of pulmonary mast cell-mediator release in the pathogenesis of EIA and to determine whether EIA is associated with enhancement of airway inflammation, we studied 11 subjects with mild stable asthma (FEV1, 93% +/- 3% predicted; mean +/- SEM) with significant EIA (after exercise fall in FEV1, 41% +/- 5%). Bronchoalveolar lavage (BAL) was performed immediately (less than 1 hour) after exercise challenge (EC) and repeated 24 hours later (exercise studies). On another occasion, paired BALs were done 24 hours apart (control studies). A minimum of 2 weeks separated the exercise and control pairs. No changes were observed in BAL cell counts, differentials, or reactive oxygen species metabolism after EC. Neither BAL histamine nor BAL tryptase levels increased, either shortly (less than 1 hour) or 24 hours after EC. We conclude that EC in subjects with asthma is not associated with cellular influx to airspace and that mechanisms other than histamine release by pulmonary mast cells may be responsible for EIA.
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PMID:Exercise-induced asthma is not associated with mast cell activation or airway inflammation. 173 Aug 41

Adverse reactions to drugs require that their mechanisms be elucidated, particularly when anaphylaxis is suspected. Early diagnosis can be achieved by plasma histamine measurements. Unfortunately, the short plasma half-life of histamine and the difficulties in handling the sample usually preclude this measurement, although a sensitive radioimmunologic kit is routinely available. It has been recently suggested that mast cell tryptase, a component of the mast cell granules, could provide an alternative to histamine determination. We have measured plasma histamine and tryptase in 19 patients who developed possible anaphylactoid reactions to anesthetic or other drugs. Eight patients had increased values for both histamine and tryptase. In 4 a muscle relaxant drug was proved responsible for the reaction. Six patients had normal levels for both substances. In each case, the clinical signs of anaphylaxis were moderate. Two patients had normal histamine and high tryptase concentrations, due to late sampling (greater than 5 h). In 2 other patients, histamine was high, with normal tryptase: in 1, muscle relaxant allergy was further demonstrated. Tryptase half-life was equal to 90 min in 3 patients. At least 15 min was necessary to reach the peak level when the responsible drug was administered intravenously. The best time for measuring tryptase was 1-2 h after the reaction (not greater than 6 h), whereas for histamine it was 10 min to 1 h. We conclude that measurement of plasma tryptase along with measurement of plasma histamine may aid in diagnosis of anaphylaxis.
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PMID:Biochemical markers of anaphylactoid reactions to drugs. Comparison of plasma histamine and tryptase. 174 15

Immunohistochemical staining of conjunctival biopsies from four normal subjects and five patients with atopic keratoconjunctivitis (AKC) was performed, using a monoclonal antibody to human mast cell tryptase. A massive hyperplasia of mast cells in the patients with AKC was demonstrated. The mean mast cell density in the normal patients was 55.6/mm2 and in the patients with AKC, 172/mm2. The appearance of large numbers of mast cells in the conjunctival epithelium of AKC patients was also demonstrated. The possible pathophysiological significance of these findings is discussed.
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PMID:Mast cell hyperplasia in atopic keratoconjunctivitis. An immunohistochemical study. 180 Jan 75

Purified mast cell carboxypeptidase cleaved the C-terminal leucines from Leu5-enkephalin (Leu-ENK), neurotensin (NT), and kinetensin (KT), with Km values of 36, 16, and 15 microM, and kcat values of 44, 51, and 53 s-1, respectively. To better predict potential in vivo hydrolysis products generated by mast cell proteases, these peptides were incubated with released skin mast cell supernatants. Leu5-enkephalin was hydrolyzed only by carboxypeptidase. Kinetensin was cleaved by tryptase, chymase, and carboxypeptidase to yield KT(1-3), KT(1-7), KT(1-8), KT(4-7), and KT(4-8), the last two peptides by the concerted action of two of the proteases. NT(1-11) and NT(1-12) were generated from neurotensin by chymase and carboxypeptidase, respectively.
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PMID:Human mast cell proteases hydrolyze neurotensin, kinetensin and Leu5-enkephalin. 180 Sep 60

Rat peritoneal mast cells (RPMC) and rat basophilic leukemia (RBL) cells are representative of connective tissue-type (CTMC) and mucosal-type (MMC) mast cells, respectively. Using polyethylene glycol, we have fused RPMC with 6-thioguanine resistant, HAT (hypoxanthine, aminopterin, thymidine) sensitive RBL-CA10.7 or RBL-CK2 cells, yielding several hybrid rat mast cell lines (HRMC). The hybridomas exhibited different size and cytoplasmic granularity when compared with parental cell lines. Analysis of both high (Fc epsilon RI) and low affinity (Fc epsilon RL) receptors for IgE revealed that the hybrid lines had more variable receptor patterns than the parent lines. Three hybridoma lines were chosen for further study. Differential histochemical staining with alcian blue and safranin O dyes indicated the hybrids to be predominantly of the MMC type: however, a few cells of one of these uncloned hybridomas were found to be of the CTMC type. Attempts to isolate the CTMC hybridomas yielded one culture which was predominantly of the CTMC phenotype and in a number of other cultures, cells were found expressing simultaneously both the CTMC and the MMC phenotype. After 3 weeks in culture, however, all hybridomas, including those which were cloned further, expressed only the MMC histochemical phenotype. This was found to correlate with the presence of rat mast cell protease II (RMCPII) and the absence of RMCPI in all hybridomas, as detected by Western blot analysis. In addition, the histamine content of all cells was significantly lower than that of the parent RPMC. Most hybrid mast cells expressed both Fc epsilon RI and Fc epsilon RL which in some cases exhibited significant variations in the Mr. These results indicate that somatic cell hybrids expressing the MMC and CTMC phenotype can be produced by the fusion of RBL and RPMC. The CTMC phenotype, however, is unstable, and possible reasons for this are discussed.
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PMID:Establishment and characterization of hybrid rat mast cells. 182 10

To establish a useful laboratory protocol to investigate possible cases of fatal anaphylaxis, we measured mast-cell-derived tryptase levels and allergen-specific immunoglobulin E (IgE) antibody levels in sera obtained prior to or within 24 h after death from 19 anaphylaxis victims. Elevated serum tryptase levels (range = 12 ng/mL to 150 micrograms/mL) were found in nine of nine Hymenoptera sting fatalities, six of eight food-induced fatalities, and two of two reactions to diagnostic therapeutic agents. Tryptase levels were normal (less than 10 ng/mL) in 57 sequential sera obtained postmortem from six control patients. Tryptase could not be measured in pleural or pericardial fluids for technical reasons. Serum IgE antibodies were elevated in five of the nine Hymenoptera sting fatalities and in eight of the eight fatal food reactions; assays were unavailable for the two diagnostic/therapeutic agents. If elevated, the victim's serum IgE antibodies to food could be used to identify allergens in uneaten portions of foods consumed shortly before the anaphylactic event. IgE antibodies were moderately stable during storage in a variety of anticoagulants at room temperature for up to 11 weeks. Elevated mast-cell-derived tryptase levels in postmortem sera reflect antemortem mast cell activation and may be used as a marker for fatal anaphylaxis. If assays are available for IgE antibodies to relevant allergens, such assays provide evidence for antemortem sensitization; these assays may be modified to identify allergens in foods consumed by victims of food-induced anaphylaxis.
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PMID:Laboratory investigation of deaths due to anaphylaxis. 185 50

Mast cells appear to promote fibroblast proliferation, presumably through secretion of growth factors, although the molecular mechanisms underlying this mitogenic potential have not been explained fully by known mast cell-derived mediators. We report here that tryptase, a trypsin-like serine proteinase of mast cell secretory granules, is a potent mitogen for fibroblasts in vitro. Nanomolar concentrations of dog tryptase strongly stimulate thymidine incorporation in Chinese hamster lung and Rat-1 fibroblasts and increase cell density in both subconfluent and confluent cultures of these cell lines. Tryptase-induced cell proliferation appears proteinase-specific, as this response is not mimicked by pancreatic trypsin or mast cell chymase. In addition, low levels of tryptase markedly potentiate DNA synthesis stimulated by epidermal growth factor, basic fibroblast growth factor, or insulin. Inhibitors of catalytic activity decrease the mitogenic capacity of tryptase, suggesting, though not proving, the participation of the catalytic site in cell activation by tryptase. Differences in Ca++ mobilization and sensitivity to pertussis toxin suggest that tryptase and thrombin activate distinct signal transduction pathways in fibroblasts. These data implicate mast cell tryptase as a potent, previously unrecognized fibroblast growth factor, and may provide a molecular link between mast cell activation and fibrosis.
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PMID:Mast cell tryptase is a mitogen for cultured fibroblasts. 186 60

To investigate the hypothesis that mast cell and neutrophil proteases stimulate airway gland secretion, we studied the effects of two mast cell proteases (tryptase and chymase) and two neutrophil enzymes (human neutrophil elastase and cathepsin G) on secretion of 35S-labeled macro-molecules from cultured bovine airway gland serous cells. Tryptase had no effect, but the other three enzymes stimulated secretion. Threshold concentrations of the enzymes (greater than or equal to 10(-10) M) were lower by two orders of magnitude than other agonists (e.g., histamine, prostaglandins, beta-adrenergic agonists). Only proteases induced maximal secretory response (greater than or equal to 80% depletion of 35S-labeled macromolecules), and these responses were greater than 10-fold larger than those of other agonists. The active catalytic sites of the enzymes are required for their secretory activities. These findings suggest a role for these enzymes in the pathogenesis of inflammatory airway diseases associated with hypersecretion, and they suggest that the use of selective site-directed inhibitors of these enzymes may provide a novel strategy for intervention in inflammatory diseases of the airways associated with hypersecretion (e.g., cystic fibrosis, chronic bronchitis).
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PMID:Role of mast cell and neutrophil proteases in airway secretion. 189 27

Tryptase is predominantly found in mast cells, where it resides in secretory granules, and is released with other mediators during mast cell degranulation. By using a newly developed commercial assay for measurements of tryptase levels we have investigated two cases of suspected drug-induced anaphylaxis. Each patient had a similar clinical presentation, consisting of hypotension and cyanosis after administration of thiopentone and suxamethonium. One of the patients showed a highly elevated serum level of tryptase reaching 26 micrograms/l 30 min after the initial reaction. In addition, slightly elevated levels of specific IgE antibodies to thiopentone were detected. The other patient with similar symptoms showed no increase in the level of tryptase, nor any specific IgE to thiopentone or suxamethonium. These data indicate the patient I suffered from true anaphylaxis, whereas the reaction of patient II occurred by a different mechanism.
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PMID:Evaluation of mast cell activation (tryptase) in two patients suffering from drug-induced hypotensoid reactions. 189 43

Dog mastocytomas (anatomic and biochemical features comparable to normal dog and human mast cells) were used to study actions of mast cell mediators on several airway effector systems. We showed mastocytoma cell adherence to both cultured tracheal epithelial cells and tracheal tissue sections for greater than 48 h that was abolished completely by pretreatment of mast cells with proteases. This mast cell-epithelial cell adhesion-interaction reaction is probably mediated by a mast cell plasma membrane protein. Mast cell mediators stimulate short circuit current and ion flux across dog tracheal epithelia mounted in Ussing chambers. Pretreatment of epithelia with indomethacin blocks this effect, probably by inhibiting LTC4-induced activation of epithelial cyclooxygenases. Mastocytoma cells also increase secretion from cultured serous submucosal gland cells. Blockade of cyclooxygenase and lipoxygenase pathways in mastocytoma cells activated by calcium ionophore does not alter secretion of the serous cells induced by mastocytoma supernatant, but secretion induced by mastocytoma supernatant or purified mast cell chymase is markedly reduced by an inhibitor of chymase. These results suggest that mast cells can alter airway secretions not only by actions on ion flux in epithelial cells but also by actions on submucosal gland secretion; this latter action appears to be mediated by mast cell chymase. Finally, supernatants from mastocytoma cells stimulated by calcium ionophore greatly increase the sensitivity and magnitude of the contractile response of dog bronchial smooth muscle to histamine. These effects are blocked by an inhibitor of mast cell tryptase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mast cells and cell-to-cell interactions in airways. 190 Jun 81


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