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)

The orientation of cytochrome b6 in the thylakoid membrane and the question of whether the number of membrane spanning helices is an even or odd number was tested through the relative trypsin susceptibility of epitopes (Asp-5 to Gln-14) and (Ile-205 to Leu-214) at the NH2 and COOH termini, respectively, of the 214-residue cytochrome b6 polypeptide. A structure of the cytochrome with an even number of helices and the NH2 and COOH termini on the stromal side of the membrane was inferred from the following: 1) cleavage of cytochrome b6 by trypsin added to thylakoids occurs by removal of both of the exposed NH2- and COOH-terminal epitopes. The epitopes at the termini were more sensitive to trypsin after prior treatment of thylakoids with carboxypeptidase A, indicating that these epitopes are shielded on the stromal side of the membrane by the COOH termini of other proteins. 2) Both epitopes were more trypsin-sensitive in thylakoid membranes than was cytochrome f that is only sensitive to trypsin acting on the lumen side of the membrane. 3) The NH2- and COOH-terminal epitopes of cytochrome b6 were also more sensitive to trypsin added to thylakoid membranes than were the oxygen-evolving complex 16- and 33-kDa proteins that are completely located on the lumen side. 4) The order of trypsin susceptibility was reversed in inside-out membranes, where the cytochrome NH2- and COOH-terminal epitopes were less sensitive than the 16- and 33-kDa proteins. The decreased relative sensitivity of the cytochrome b6 epitopes occurs in spite of a greater absolute sensitivity of these epitopes to trypsin in inside-out membranes. 5) The greater absolute sensitivity can be explained by a 4-helix model that includes trypsin-sensitive sites on the lumen side.
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PMID:Thylakoid membrane protein topography. Location of the termini of the chloroplast cytochrome b6 on the stromal side of the membrane. 169 78

To assess whether mast cell and eosinophil (EOS) degranulation occurs in the airway of subjects with moderately symptomatic asthma, we have measured levels of preformed mast cell-derived mediators (histamine and tryptase) and EOS-derived mediators (major basic protein and EOS-derived neurotoxin) in bronchoalveolar lavage fluid (BALF) obtained from patients with symptomatic (N = 14) and asymptomatic asthma (N = 9) and patients without asthma (N = 6). Both the FEV1 (1.52 +/- 0.33 L:55% +/- 15% of predicted FEV1) and the forced expiratory flow at 50% (FEF50) (1.11 +/- 0.62 L/sec:26% +/- 14% of predicted FEF50) in the patients with symptomatic asthma were significantly lower than the corresponding values for FEV1 (3.16 +/- 0.45 L:86% +/- 10% of predicted FEV1) and the FEF50 (4.04 +/- 1.54 L/sec:71% +/- 25% of predicted FEF50) in the patients with asymptomatic asthma. Levels of histamine (4.8 +/- 5.0 ng/ml versus 0.2 +/- 0.2 ng/ml) (p = 0.05), EOS-derived neurotoxin (420.6 +/- 959.4 ng/ml versus 12.6 +/- 7.7 ng/ml) (p = 0.05), major basic protein (31.4 +/- 46.6 ng/ml versus less than 9 ng/ml) (p = 0.05), and percent EOSs (10.6% +/- 7.0% versus 1.1% +/- 0.9% of BAL cells) (p = 0.0006) were all significantly elevated in BALF from symptomatic compared to asymptomatic patients with asthma. The elevated levels of tryptase (13.2 +/- 14.8 ng/ml versus 3.9 +/- 3.9 ng/ml) in BALF from symptomatic compared to asymptomatic patients with asthma approximated, but did not reach, statistical significance. Spontaneous histamine release from BAL mast cells of symptomatic patients with asthma was 46% +/- 5% compared to 5% +/- 2% in asymptomatic patients with asthma. In response to antihuman IgE, histamine release from BAL mast cells recovered from asymptomatic patients with asthma increased to 25% +/- 10%, whereas in BAL mast cells of symptomatic patients with asthma, no anti-IgE potentiation of histamine release occurred. This study suggests that mast cell and EOS degranulation is ongoing in the airway of patients with moderately symptomatic asthma.
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PMID:Evidence of ongoing mast cell and eosinophil degranulation in symptomatic asthma airway. 171 32

From current information, a number of conclusions can be drawn. Antigen activation of the allergic reaction in the airways is associated with an immediate rise in mast cell derived mediators, including histamine and tryptase. Associated with antigen activation of the allergic reaction is recruitment of eosinophils to the airways. This can best be seen in the airway lavage 48 hours after challenge with antigen. An increased presence of eosinophils suggests that they are an important contributor to the late allergic reaction and may be one of the major constituents in the development of bronchial inflammation. Although many factors participate in the late allergic inflammatory response, eosinophil-derived proteins are known to cause airway injury. Regulation of eosinophils in this process is not clearly established; however, our findings of increased IL-5 in relationship to the presence of eosinophils and their granular proteins suggests that this cytokine may be an important modulator of eosinophil function and activation following allergen challenge. However, much remains unknown in understanding bronchial inflammation and the eosinophil's role in the process. In conclusion, the eosinophil is a major cellular participant in late phase allergic airway disease. Its presence and known functions suggest that the eosinophil is a significant cellular factor in the development of allergic airways disease in asthma. Further advances in this area will follow continued studies, particularly those which involve biopsy and correlation with airway physiology.
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PMID:The role of eosinophils in the pathophysiology of asthma. 171 54

The involvement of mast cells in the pathogenesis of aspirin (ASA)-induced respiratory reactions was investigated by measuring serum levels of tryptase, a neutral protease that is a specific marker of mast cell activation. ASA challenges were performed in 17 ASA-sensitive patients with asthma and rhinosinusitis, and tryptase and histamine levels were measured in their venous blood samples. In three subjects who experienced moderate to severe respiratory reactions extending to the skin and/or gastrointestinal tract, marked elevations of tryptase levels in postreaction serum samples (peak levels, 51.9 and 40.0 ng/ml) were discovered in two of these three subjects, and a small elevation of tryptase occurred in the serum of the third subject (3.1 ng/ml peak). Plasma histamine levels in postreaction samples were significantly elevated over baseline values in all three subjects (delta mean plasma histamine, 238 pg/ml versus 56 pg/ml for the remaining 14 subjects; p less than 0.04). In the remaining 14 subjects, who experienced similar respiratory reactions without extrapulmonary symptoms during aspirin challenge, changes in tryptase and histamine levels were not observed.
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PMID:Tryptase and histamine release during aspirin-induced respiratory reactions. 172 Jul 95

Besides its effects on tumour cells, tumour necrosis factor (TNF) also acts on a variety of other cells, thus enhancing inflammatory and immune processes. In view of the prominent role of the mast cell in such processes, the aim of the present study was to assess the effects of recombinant TNF-alpha on human mast cells. Mast cells from the infant foreskin obtained during circumcision were dispersed by an enzymatic technique using collagenase and hyaluronidase. Cells thus obtained were pooled, washed and separated by Percoll gradient centrifugation. Mast cells, with a purity of 70-90% were incubated for 60 min with 10(-11) to 10(-7) M rTNF-alpha. Histamine and tryptase levels were assessed in the cell supernatant by spectrofluorometry and radioimmunoassay (RIA) respectively. A concentration dependent release of histamine was observed, which reached a maximum of 11.5 +/- 2.2 nmol/10(6) cells at 10(-8) M rTNF. Release of tryptase was also concentration dependent and reached a maximum of 293 +/- 105 mU/10(6) cells (10(-8) rTNF). rTNF-alpha thus appears to be a direct stimulus for mast cells to degranulate and to release both histamine and tryptase.
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PMID:Tumour necrosis factor stimulates human skin mast cells to release histamine and tryptase. 172 44

Mast cells are widely distributed in various organs. Two classes of mast cells, the mucosal mast cell (MMC) and the connective tissue mast cell (CTMC), have been shown to exist in the intestine of experimental animals. In the present study, we investigated the method of staining suitable for observing the mast cells distributing in the nasal mucosa, and also examined by the use of two fixatives whether the mast cells have properties of MMC or those of CTMC. A neutral buffered formalin solution and Carnoy's solution were used as fixative. For staining, five solutions, i.e., toluidine blue (TB) solution (pH 0.5, 2.5, and 4.0), 0.4 M MgCl2-alcian blue (AB) solution, and naphthol AS-D chloracetate (NAS-DC) solution, were tested. In the specimen fixed with Carnoy's fixative, staining with pH 0.5 TB showed the largest number of mast cells in all mucosal layers, particularly in the epithelial layer. The number of these mast cells agreed with that of the cells positive to pH 0.5 AB and also with that of the tryptase-positive cells stained immunohistochemically with a mouse monoclonal antitryptase antibody. Compared with formalin-fixed specimens, those fixed with Carnoy's fixative and stained with pH 0.5 TB showed significantly (p less than 0.01) many mast cells in the epithelial layer and in the subepithelial layer of lamina propria. To identify mast cells in the nasal mucosa with nasal allergy, fixation with Carnoy's fixative and staining with pH 0.5 TB were found to be most effective and simplest.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Study on staining methods for mast cells in the nasal mucosa. 172 84

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

The inhibitory effect of various dipeptides on the neurotensin-degrading metallopeptidase, endopeptidase 24.16, was examined. These dipeptides mimick the Pro10-Tyr11 bond of neurotensin that is hydrolyzed by endopeptidase 24.16. Among a series of Pro-Xaa dipeptides, the most potent inhibitory effect was elicited by Pro-Ile (Ki approximately 90 microM) with Pro-Ile greater than Pro-Met greater than Pro-Phe. All the Xaa-Tyr dipeptides were unable to inhibit endopeptidase 24.16. The effect of Pro-Ile on several purified peptidases was assessed by means of fluorigenic assays and HPLC analysis. A 5 mM concentration of Pro-Ile does not inhibit endopeptidase 24.11, endopeptidase 24.15, angiotensin-converting enzyme, proline endopeptidase, trypsin, leucine aminopeptidase, pyroglutamyl aminopeptidase I and carboxypeptidase B. The only enzyme that was affected by Pro-Ile was carboxypeptidase A, although it was with a 50-fold lower potency (Ki approximately 5 mM) than for endopeptidase 24.16. By means of fluorimetric substrates with a series of hydrolysing activities, we demonstrate that Pro-Ile can be used as a specific inhibitor of endopeptidase 24.16, even in a complex mixture of peptidase activities such as found in whole rat brain homogenate.
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PMID:Specific inhibition of endopeptidase 24.16 by dipeptides. 176 Oct 32

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


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