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)

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

Over the past decade, it has become increasingly recognized that airways inflammation is one of the major components of asthma. Until recently, measurements of bronchial responsiveness and mediators of allergic reactions were the only methods of studying pathogenetic mechanisms in asthma. With improved diagnostic procedures such as fiberoptic bronchoscopy, it has become possible to investigate these mechanisms and the resulting inflammatory changes in situ. BAL has highlighted the presence of mast cells and eosinophils and has given proof of their mediator participation in airways inflammation and hyperresponsiveness. Endobronchial biopsies have so far yielded results that are similar to those obtained from postmortem studies, although it appears that there are varying degrees of inflammation in living asthmatics. Even in mild disease, the histopathologic features of bronchial asthma are consistent with chronic inflammation. Indirect evidence obtained from allergen challenge leading to increased bronchial hyperresponsiveness during LAR, and direct evidence of inflammatory cells and their mediators in the airway mucosa and lumen after allergen challenge argue for an active role of cells in bringing about inflammatory changes. At present, however, it is not possible to relate precisely the findings obtained by bronchoscopy to the clinical presentation and progression of asthma. Cell activation with production of potent mediators of inflammation may be more relevant to inflammation than the simple presence of these cells in the airways. Almost all the inflammatory cells present in the bronchial wall and lumen have been implicated in the pathogenesis of mucosal inflammation in asthma, but with our current state of knowledge, none can be singled out as the most important contributor. The mast cell was the first to be investigated in depth, and despite the accumulation of large amounts of data concerning its ultrastructure and function, it remains uncertain to what extent this cell is involved in inflammatory responses. Thus, while its main role appears to be that of initiator of allergen-induced responses, the eosinophil has attracted more attention as a proinflammatory cell rather than as an antiinflammatory cell with a capacity to be selectively recruited from the circulation in response to IgE-dependent signals. The eosinophil secretes potent mediators that cause damage to the bronchial epithelium and lead to bronchoconstriction. The role of other cells is at present not as well defined.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mucosal inflammation in asthma. 220 Mar 18

Mast cell tryptase is a secretory granule associated serine protease with trypsin-like specificity released extracellularly during mast cell degranulation. To determine the full primary structure of the catalytic domain and precursor forms of tryptase and to gain insight into its mode of activation, we cloned cDNAs coding for the complete amino acid sequence of dog mast cell tryptase and a second, possibly related, serine protease. Using RNA from dog mastocytoma cells, we constructed a cDNA library in lambda gt 10. Screening of the library with an oligonucleotide probe based on the N-terminal sequence of tryptase purified from the same cell source allowed us to isolate and sequence overlapping clones coding for dog mast cell tryptase. The tryptase sequence includes the essential residues of the catalytic triad and an aspartic acid at the base of the putative substrate binding pocket that confers P1 Arg and Lys specificity on tryptic serine proteases. The apparent N-terminal signal/activation peptide terminates in a glycine. A glycine in this position has not been observed previously in serine proteases and suggests a novel mode of activation. Additional screening of the library with a trypsinogen cDNA led to the isolation and sequencing of a full-length clone apparently coding for the complete sequence of a second tryptic serine protease (DMP) which is only 53.4% identical with the dog tryptase sequence but which contains an apparent signal/activation peptide also terminating in a glycine. Thus, the proteases encoded by these cloned cDNAs may share a common mode of activation from N-terminally extended precursors.
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PMID:Molecular cloning of dog mast cell tryptase and a related protease: structural evidence of a unique mode of serine protease activation. 250 77

Lung mast cell hyperplasia and fibrosis is induced by bleomycin lung injury. The role of the mast cell in this process of injury and resultant fibrosis is unclear. Mutant mi/mi mice, profoundly mast-cell-deficient, were treated with intraperitoneal bleomycin and demonstrated minimal acute inflammatory and chronic fibrotic responses. Lung histamine values determined at 14 and 42 days after bleomycin injury in mi/mi mice were not increased compared to untreated mi/mi animals. However, lung histamine levels in normal mice demonstrated a 300% increase over controls on Day 14 after bleomycin injury, and then returned to baseline by Day 42. The mi/mi BAL cell recovery at 2 weeks after injury and lung hydroxyproline levels at 4 weeks after injury were not altered from baseline. The normal litter mates, in contrast, demonstrated significant increases compared to controls in both of these parameters (p < 0.01, p < 0.04). Although the mi/mi mouse is also deficient in basophils, natural killer cells and functional osteoclasts, there is no evidence of lowered pulmonary defense mechanism and neutrophils and alveolar macrophages are present in normal numbers. This investigation supports the hypothesis that the mast cell contributes to bleomycin-induced lung injury and fibrosis.
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PMID:Bleomycin injury of the lung in a mast-cell-deficient model. 750 64

Inhaled corticosteroids are now first-line therapy for most patients with asthma. However, it has been shown that there is ongoing airway inflammation and airway hyperresponsiveness even in the presence of low dose inhaled corticosteroids. To ensure a maximal therapeutic potential we investigated the effect of 3 mo of a very high dose of a new inhaled corticosteroid, fluticasone propionate (FP) (equivalent to 4,000 micrograms daily of beclomethasone dipropionate [BDP]. Twenty asthmatics with mild-to-moderate disease were recruited into this single-blind study. Baseline data were compared with those from 26 normal subjects. Differences in inflammatory indices between asthmatics and normal subjects were detected in both BAL and endobronchial biopsies. After the FP treatment period there was a significant improvement in symptom scores, lung function, and airway responsiveness by a mean 2.8 doubling dilutions of methacholine. Reduction in the airway lymphocyte load and lymphocyte activation was demonstrated and is likely to be an important mechanism mediating the effects of inhaled corticosteroids. Decreased mast cell numbers and activity in atopic asthma suggest that corticosteroids may have additional targets in different types of asthma. Reduced lymphocyte and mast cell activity was found with high dose FP even in those receiving low dose maintenance BDP prior to the study, suggesting a dose-response effect of inhaled corticosteroids on airway inflammation. BAL eosinophilia was still present after FP, indicative of a component of asthmatic airway inflammation that is relatively resistant to corticosteroid therapy.
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PMID:Effect of high dose inhaled fluticasone propionate on airway inflammation in asthma. 759 61

While LCF is present in BAL early after antigen challenge, we know little about its other potential effects beyond CD4+ T cell, monocyte, and eosinophil chemotaxis and monocyte and CD4+ T cell activation. The work described here focuses on the hypothesis that the secreted protein products of T cells participate in the airway inflammatory process that underlies human asthma, and in particular that LCF could play an early role because of the unusual responsiveness of LCF-producing T to histamine. To date, most studies have addressed the measurement of cytokines derived from CD4+ T cells (e.g., IL-2, IL-3, IL-4, IL-5, and GM-CSF) in the airways of asthmatics, and attempted to correlate the presence of protein or mRNA with the complexion of the inflammatory infiltrate. These studies have been based upon the reports that there are increased numbers of CD4+ T cells in the airways of asthmatics, and that the presence of eosinophils might correlate with the secretion of TH2-type cytokines like IL-3, -4, and -5. Using this information as a background, our work has approached the problem in an entirely different way. We have focused our attention on the early events in antigen-induced asthma that are responsible for CD4+ cell accumulation in the lung, including CD4+ T cells, eosinophils, and monocytes. We have attempted to identify mechanisms by which mast cell mediators, in particular histamine, might play a role in the secretion of chemotactic lymphokines that are selective for CD4+ cells by using CD4 itself as a chemotactic factor receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine binding to CD4+ inflammatory cells: implications for asthma. 795 94

Hypertonicity of airway lining fluid has been suggested as the stimulus for bronchoconstriction in exercise-induced asthma. We explored the airway effects of delivering a direct hypertonic stimulus to asthmatic airways via a fiberoptic bronchoscope, comparing hypertonic saline challenge by direct instillation with local aerosol delivery. A group of 18 asthmatic subjects responsive to inhaled hypertonic saline with a history of EIA were studied; the first 9 subjects received local challenge with hypertonic saline by direct instillation, and the next 9 subjects were challenged by local aerosol delivery. A control challenge with isotonic saline by either instillation or aerosol was performed at a same bronchoscopy. Local challenge with hypertonic saline by aerosol delivery was found to be more effective in inducing local bronchoconstriction (8 of 9 subjects) than instillation (2 of 6 subjects). Paired BAL fluid samples and bronchial biopsies were obtained in total of 11 and 9 subjects, respectively. Local challenge with hypertonic saline either by instillation or aerosol produced no significant change in histamine, tryptase, or PGD2 levels in BAL fluid or mast cell numbers and degranulation in bronchial biopsies. A significant correlation was observed between histamine levels in BAL fluid and airway responsiveness to inhaled hypertonic saline (rs = -0.59, p < 0.05). Bronchial biopsies showed evidence of extensive epithelial damage; however, this was not related to airway responsiveness to inhaled hypertonic saline.
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PMID:Airway effects of local challenge with hypertonic saline in exercise-induced asthma. 814 36

In order to evaluate the degree of mast cell infiltration and determine their granulation state in the airways of patients with chronic bronchitis, bronchoscopy was performed in 25 chronic bronchitis subjects (10 smokers and 15 ex-smokers) with mucoid sputum production and in seven normal nonsmoking control subjects. Bronchoalveolar lavage and bronchial biopsies were examined using histochemical techniques. Subjects with chronic bronchitis had higher numbers of mast cells both in the epithelium (1.22 +/- 1 versus 0.22 +/- 0.2 mast cells per mm) and in the bronchial glands (137.4 +/- 37.9 versus 38 +/- 5.1 mast cells per mm2) than did control subjects (p < 0.01 and p < 0.001, respectively), whereas the numbers of mast cells in bronchoalveolar lavage (0.21 +/- 0.1 versus 0.18 +/- 0.1 mast cells percentage, nonsignificant [NS]) and in the lamina propria (87.5 +/- 66.4 versus 87.2 +/- 61.8 mast cells per mm2, NS) were similar in the two groups. In the smoking group of bronchitics an increase in mast cell numbers was observed in epithelium (1.6 +/- 1.3 versus 0.95 +/- 0.7 mast cells per mm, NS), in lamina propria (112.2 +/- 86.5 versus 71.7 +/- 45.7 mast cells per mm2), and in BAL (0.26 +/- 0.21 versus 0.16 +/- 0.17 mast cell percentage of total cells, NS) in comparison with the ex-smoker's group of bronchitics.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mast cells in the airway lumen and bronchial mucosa of patients with chronic bronchitis. 817 72

Idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) is characterized by air space inflammation and fibrosis of unknown origin. The pathogenesis of the inflammatory reaction and fibrosis in fibrotic lung disorders remains unclear; however, recent attention has focused on the potential role of the mast cell in the genesis of fibrosis. To determine whether mast cells are implicated in the pathogenesis of BOOP, mast cells were identified in BAL fluid and in transbronchial lung biopsy specimens from 11 patients affected by BOOP and 17 control subjects. Mast cells and tryptase were significantly increased in BAL fluid of patients with BOOP (p = 0.001 and p = 0.03, respectively). In lung tissue of patients with BOOP, there was an increased number of mast cells per square millimeter of lung tissue with respect to control group (p = 0.001). Seventy-three percent of mast cells were found in the alveolar septa, 18% within alveoli often plunged in organizing pneumonia, 4% among alveolar lining cells, and 6% along blood vessels. No mast cells were located within alveoli in control subjects. Mast cell degranulation was evident in lung tissue specimens of patients with BOOP but not in those of control subjects (p = 0.01). This study shows the importance of mast cells and mast cell activation in the pathogenesis of BOOP.
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PMID:Mast cells in bronchiolitis obliterans organizing pneumonia. Mast cell hyperplasia and evidence for extracellular release of tryptase. 869 38

Epidemiological data indicated that allergic rhinitis often coexists with and may precede the development of reactive airway disease. In particular, ARP with BHR are more likely to develop asthma. However, the pathogenesis of BHR associated with allergic rhinitis is still remains uncertain. Therefore we designed the study on ARP with/without BHR. The aim of this study were to investigate the presence of an inflammatory process in lower respiratory tract in ARP and to relate these changes to airway responsiveness Eleven ARP with BHR (Group I), eleven ARP without BHR (Group II) and two control patients (Control group) were studied. All of the ARP were judged atopic on the basis of positive skin prick test to common inhalant allergens. Bronchial challenges were performed with increasing concentration of M. All the subjects underwent fiberoptic bronchoscopy, BAL and bronchial biopsies were obtained for pathologic examination. The mean total cell and the mean percentage of macrophages, lymphocytes, neutrophils and eosinophils in BAL fluid were in normal range in all groups without any significant differences between the groups. There weren't any correlation between PC20 to M and the total cell counts and percentage counts of these cells. In bronchial biopsy samples, the absolute numbers of lymphocytes, neutrophils, eosinophils and mast cells in the submucosa showed no differences between the three groups. The epithelial shedding was more extensive in ARP than control subjects (p = 0.05). The thickness of the epithelium was prominent in Group I (p < 0.05) but there was no significant differences in the basement membrane thickening between the three groups. We could only find an inverse correlation between PC20 to M and the mast cell counts in the submucosa (r xy:-0.815 p < 0.05). In conclusion, we couldn't observe any prominent morphological changes which indicate that may cause of BHR in ARP except the increased epithelial shedding in Group I. However, the increased epithelial shedding is not a reliable criterion to comment because of the possibility of mechanical damage of bronchial biopsies caused by the forceps.
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PMID:The mechanism of bronchial hyperreactivity in allergic rhinitis patients. A light microscopic study on BAL and bronchial biopsy. 893 89


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