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)

In order to investigate the mechanism of adenosine-induced bronchoconstriction in asthma, serum neutrophil chemotactic activity (NCA) was measured in normal individuals and patients with asthma before and 5 min after bronchoprovocation testing with adenosine. Challenge testing was terminated when the FEV1 fell by 20% or a concentration of 10 mg/ml was reached. Participants were separated into three groups: six asthmatics hyperresponsive to adenosine (Group 1), seven asthmatics hyperresponsive to histamine but not adenosine (Group 2), and six normal subjects (Group 3). The mean percentage increase in NCA was 84% for Group 1 (p less than 0.001), 29% for Group 2 (p less than 0.05), and only 13% for Group 3. No significant increase in NCA was observed after histamine challenge in seven individuals with asthma derived from Groups 1 and 2. Four patients from Group 1 were rechallenged after treatment with therapeutic doses of oral theophylline. Theophylline therapy was associated with a significant attenuation of the increase in NCA at the concentration of adenosine which caused a 20% decrease in FEV1 before treatment (18% versus 84%, p less than 0.01). The concentration of adenosine which caused a 20% drop in FEV1 was increased at least twofold for each of the four patients. Analysis of NCA by gel filtration chromatography demonstrated an increase in a high molecular weight neutrophil chemotactic factor in the serum of two Group 1 patients after adenosine challenge. Release of a high molecular weight neutrophil chemotactic factor is consistent with a mast cell source for inflammatory mediators in adenosine-induced bronchoconstriction. The therapeutic effects of theophylline, a potent adenosine antagonist, in asthma may therefore occur in part through the inhibition of this process.
 ...
PMID:Bronchial challenge with adenosine causes the release of serum neutrophil chemotactic factor in asthma. 202 8

A 24 year old man developed severe asthma two years after starting to work in a plywood plant. Four years later the patient had to stop working because of the increasing severity of his asthma. Three months after leaving his job, the patient's asthma was greatly improved. His job consisted of placing plywood sheets into a drying machine. The plywood sheets had stayed outside in wet conditions for at least four to six weeks and were usually covered with moulds. Drying the plywood sheets changed the mould into a fine orange powder. Exposure to this in the laboratory induced an isolated immediate asthmatic reaction. The same reaction was seen when the patient was challenged with an extract of the mould powder at a 0.1% w/v concentration. Skin prick test with the mould extract induced a weal and flare reaction and IgE antibodies against the dry mould powder were identified. A control patient with the same degree of bronchial hyperreactivity did not have any asthmatic reaction when challenged with the same mould extract. Culture of the dry mould powder on Sabouraud agar plates grew pure Neurospora sp. This mould has not been previously reported as a cause of occupational asthma. The immunological mechanism is probably related to an IgE mediated mast cell allergy.
 ...
PMID:Occupational asthma caused by exposure to neurospora in a plywood factory worker. 202 96

We quantitated serum neutrophil chemotactic activity (NCA), which is associated with mast cell or basophil activation, to determine if mast cell or basophil mediators are released during bronchoprovocation-inhalation challenge with subirritant levels of toluene diisocyanate (TDI). Four subjects with suspected TDI-induced asthma and four mite-sensitive subjects with asthma who served as a comparison group were studied. NCA was measured in a multiwell, microchemotaxis chamber. Blood samples were collected, and FEV1 measurements were performed before challenge and at regular intervals during the subsequent 24 hours. Three of four workers clinically sensitive to TDI reacted to a subirritant TDI exposure. There was no increase in NCA during placebo challenges. NCA increased in the three TDI-sensitive workers during early and late asthmatic reactions in quantities proportional to the FEV1 decline. No increase in NCA was found during TDI exposures in the TDI-negative worker. Gel filtration analysis demonstrated the main NCA fraction eluted with macromolecules of an estimated molecular weight greater than 440,000 daltons. This characteristic is compatible with neutrophil chemotactic factor of basophil or mast cell origin. The kinetics of NCA release were similar in mite- and TDI-induced asthmatic reactions. A high correlation (r = 0.97; p = 0.0006) was obtained between the percent decrease in FEV1 during early asthmatic reactions and percent increase in NCA. These observations support the hypothesis that activation of mast cells or basophils is associated with TDI-induced early and late asthmatic reaction.
 ...
PMID:Neutrophil chemotactic activity in toluene diisocyanate (TDI)-induced asthma. 215 57

We have investigated the ability of salbutamol to protect against bronchoconstriction induced by methacholine, histamine, and adenosine 5'-monophosphate (AMP) in nine subjects with asthma. In a double-blind, placebo-controlled study, salbutamol, 2.5 mg administered by nebulization, increased the geometric mean provocation concentrations of methacholine, histamine, and AMP required to produce a 20% decrease in FEV1 from 0.3 to 2.2, 0.4 to 3.8, and 4.0 to 106.7 mg/ml after placebo and active treatment, respectively (p less than 0.01). Thus, this dose of beta 2-adrenoceptor agonist displaced the concentration-response curves for methacholine, histamine, and AMP to the right in a parallel fashion by 8.8 (0.6 to 29.3)-, 10.3 (1.4 to 33)-, and 26.6 (1.5 to 76.6)-fold, respectively, the difference between the results for AMP and those for histamine and methacholine being statistically significant (p less than 0.01). For six of the nine subjects studied, salbutamol displaced the concentration-response curve for AMP to the right by greater than 50-fold. There was no correlation between bronchodilatation and protection against bronchoconstriction induced by any of the agonists. We conclude that salbutamol protects against bronchoconstriction provoked by methacholine and histamine by functional antagonism, whereas with AMP, an additional activity is demonstrable, possibly involving inhibition of mast cell-mediator release.
 ...
PMID:Comparative protective effect of the inhaled beta 2-agonist salbutamol (albuterol) on bronchoconstriction provoked by histamine, methacholine, and adenosine 5'-monophosphate in asthma. 218 97

Recent studies have shown that inhaled frusemide exerts a protective effect against various bronchoconstrictor stimuli in asthma including exercise, fog and allergen. Since mast cell activation seems to be a component of bronchoconstriction by these stimuli it is possible that inhibition of mediator release accounts for some or all of the inhibitory effects of frusemide in asthma. Since inhaled adenosine 5'-monophosphate (AMP) is another stimulus that produces bronchoconstriction by augmenting mast cell mediator release, we have investigated the ability of this drug to antagonise the airway effects of inhaled AMP and methacholine in a randomized, placebo-controlled, double-blind study of 12 asthmatic subjects. Inhaled frusemide (approximately 28 mg) administered 5 min prior to challenge increased the provocation concentration of inhaled AMP and methacholine required to reduce forced expiratory volume in one second (FEV) by 20% from baseline from 30 to 96 mg.ml-1 (p less than 0.01) and from 1.1 to 1.8 mg.ml-1 (p less than 0.01), respectively. The protection that frusemide afforded against AMP was significantly greater than that against methacholine (p less than 0.05). These data suggest that inhaled frusemide may serve as a functional antagonist against a smooth muscle spasmogen, such as methacholine, possibly by augmenting prostanoid generation. Its more potent activity against AMP and other bronchoconstrictor stimuli, that are considered to involve mast cell mediators, suggests an additional action on mast cell functions possibly at the level of the Ca++/Mg(++)-ATPase.
 ...
PMID:Inhibition of adenosine 5'-monophosphate- and methacholine-induced bronchoconstriction in asthma by inhaled frusemide. 215 Oct 34

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)
 ...
PMID:Mucosal inflammation in asthma. 220 Mar 18

In the trachea and bronchi of the atropinized rat, the proportion of degranulating mast cells (defined as having one or more granules outside the body of the cell in a 10-microns thick section) was increased from 35-40% to 48-55% following electrical stimulation of one or both vagus nerves for 3 min. The increase occurred bilaterally, though it was greater on the stimulated side. The degranulation of mast cells was prevented by transection of the nerve rostral to the nodose ganglion 8-10 days before stimulation. Pre-treatment of rats with capsaicin also prevented the degranulation of mast cells that otherwise would have followed stimulation of the vagus nerve. These observations indicate that tracheo-bronchial mast cells discharge their granules in response to the activity of capsaicin-sensitive axons of neurons whose cell bodies are rostral to the nodose ganglion. These are probably substance P-containing polymodal nociceptive neurons of the jugular ganglion. If similar neurons exist in man, axon reflexes in their intrabronchial branches would be expected to stimulate the release of mast cell-derived agents that cause bronchoconstriction in asthma.
 ...
PMID:Degranulation of mast cells in the trachea and bronchi of the rat following stimulation of the vagus nerve. 221 Aug 75

Inhaled adenosine 5'-monophosphate (AMP) induces bronchoconstriction in subjects with asthma, probably caused by histamine release from airway mast cells, and repeated AMP bronchial challenge leads to attenuation of the bronchoconstrictor response. Since exercise-induced bronchoconstriction may be mediated by hypertonic mast cell degranulation, we postulated that repeated AMP bronchial challenge should reduce the response to subsequent exercise challenge. Eight atopic subjects with asthma took part in an unblinded, randomized trial. On the control study day, a treadmill exercise test previously demonstrated to induce a greater than 20% fall in FEV1 was performed. On the AMP study day, three AMP dose-response bronchial challenges were performed at 1-hour intervals. Each AMP challenge was continued until either a provocative concentration causing a 20% fall in FEV1 had been achieved (PC20) and the PC20 was calculated, or the maximum concentration of AMP (400 mg/ml) had been administered. After recovery of the FEV1 from AMP challenge, a treadmill exercise test identical to the test on the control study day was performed. On the AMP study day, the geometric mean PC20 was 15.3 (7.9 to 29.5) mg/ml for the first test, and 28.2 (10.7 to 77.4) mg/ml for the third test (not significant). On the control study day, the mean maximum percentage fall in FEV1 after exercise was 28.0% +/- 2.7%, whereas on the AMP study day, it was reduced to 13.0% +/- 4.3% (p less than 0.01). A significant correlation was found between the change in responsiveness to AMP induced by repeated challenge and the attenuation of the subsequent exercise response (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Repeated exposure of asthmatic airways to inhaled adenosine 5'-monophosphate attenuates bronchoconstriction provoked by exercise. 221 8

We have used fiberoptic bronchoscopy to obtain endobronchial biopsies in which mast cells and eosinophils were enumerated using monoclonal antibodies directed against mast cell tryptase (AA1) and the eosinophil cationic protein (EG2). Eleven symptomatic atopic asthmatics treated with beta 2-agonists alone and six normal subjects were studied. Over a period of 2 wk prior to bronchoscopy, patients recorded asthma symptom scores, bronchodilator usage, and twice-daily peak expiratory flow. Five days before bronchoscopy, methacholine responsiveness was assessed. Two biopsies were taken from the subcarinae, one of which was processed into araldite for immunostaining by the streptavidin biotin immunoperoxidase method and the other into Spurr resin for electron microscopy. The number of AA1 staining mast cells present in the bronchial mucosa was not significantly different in the epithelium or submucosa between the asthmatic and the normal subjects. However, in the biopsies from asthmatics, there were significantly greater numbers of EG2-staining eosinophils in the epithelium (median, 1.2/mm versus zero; p less than 0.005) and in the submucosa (median, 50/mm2 versus 1/mm2; p less than 0.001). Electron microscopy showed morphologic features of mast cell and eosinophil degranulation in the asthmatics. No correlation could be established between mast cell or eosinophil numbers and indices of disease activity of PC20 methacholine, which points to the complexity of mechanisms responsible for the symptoms and the airway hyperresponsiveness of asthma.
 ...
PMID:Quantitation of mast cells and eosinophils in the bronchial mucosa of symptomatic atopic asthmatics and healthy control subjects using immunohistochemistry. 202 38

Mast cells are the repository for histamine in the body. They influence the pathophysiology of allergic diseases, such as rhinitis, urticaria, and asthma; regulate bone formation and integrity; help repair and maintain connective tissue; promote wound healing; and probably contribute to the development and preservation of the endothelium and small blood vessels. Although they are found in all human tissue, mast cells are most prevalent at the interface between the host and its environment, that is, in the skin and in the mucosa of the upper and lower respiratory tracts and the gastrointestinal tract. Recent evidence suggests that two types of mast cells exist: (1) the connective tissue type, found primarily but not exclusively in loose connective tissue and skin, and (2) the mucosal type, found primarily in gastrointestinal mucosa and peripheral airways. The factors that produce this differentiation are not fully known. Although both mast cell types have IgE receptors that can be activated by allergens, differences between the two types exist in their responses to nonallergic signals, the mediators they release, their proteoglycan constituents, and the makeup of their granular enzymes. The importance of these biochemical differences to cellular functioning remains to be investigated.
 ...
PMID:Mast cell biology. 222 21


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>