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)

Mast cells were isolated by enzymatic digestion from lung tissue obtained from patients with chronic obstructive lung disease and from normal subjects. Two mast cell subtypes could be demonstrated in human lung tissue. Mast cell subtypes were differentiated in formalin-sensitive and formalin-insensitive mast cells. It appeared that compared with normal individuals, patients suffering from chronic bronchitis had increased numbers of mast cells of the formalin-sensitive type, whereas patients with emphysema had reduced numbers, but the same ratio, of both mast cell subtypes.
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PMID:Patients with chronic bronchitis differ in their mast cell subtypes as compared with normal subjects. 271 49

Ponies with recurrent airway obstruction (principal ponies) and their controls were given aerosolized Micropolyspora faeni antigen via endotracheal tube during a period when the principal ponies were in disease remission. In both groups of ponies, we performed bronchoalveolar lavage (BAL) and measured pulmonary function at base line, and 5 hours after aerosol administration of 30 ml of 0.9% NaCl solution or 30 ml of 1% w/v particulate M faeni antigen in 0.9% NaCl solution. In both groups of ponies, aerosolized M faeni antigen increased WBC count, neutrophil numbers, and albumin concentration in BAL fluid, but macrophage numbers decreased. In the principal ponies, BAL mast cell numbers were decreased 5 hours after administration of M faeni antigen. The M faeni antigen had no effect on the mechanical properties of the lungs or on gas exchange in the control ponies, but did increase respiratory frequency minute ventilation and pulmonary resistance, and decreased arterial oxygen tension in the principal ponies. Changes in pulmonary function were apparent only in the principal ponies, which suggests that neutrophils, per se, do not cause pulmonary dysfunction and that M faeni may be one of the etiologic agents involved in chronic obstructive pulmonary disease.
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PMID:Aerosolized Micropolyspora faeni antigen as a cause of pulmonary dysfunction in ponies with recurrent airway obstruction (heaves). 340 Sep 31

Hyperreactivity of the bronchial tree is a common characteristic in chronic obstructive lung disease. The mechanism underlying this phenomenon may be a disturbed equilibrium between contracting and relaxing forces acting upon the effector organ, the bronchial smooth muscle. The most important bronchial obstructive forces result from an increased vagal activity and from mediator release from the mast cell. The adrenergic system may be considered as a counter-regulating force inducing a bronchodilatation. This system was studied by challenge tests with histamine, acetylcholine, and propranolol. Special attention will be paid to the relationship between the propranolol response and allergic characteristics in asthmatic patients.
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PMID:Some aspects of the regulation of the bronchial tree in obstructive lung disease: an introduction. 629 Feb 49

Bronchial asthma is characterized by a chronic inflammation with accumulation of eosinophils, mast cells and activated T lymphocytes that release a large panel of cytokines. As the mucosal immune system comprises a series of specialized lymphoid tissues with a well-identified lymphocyte traffic between different compartments, we initiated a study to evaluate the histological abnormalities of minor salivary glands (MSGs) in patients with bronchial asthma. 58 patients were studied (29 with allergic asthma, 29 with nonallergic asthma) and compared to 15 healthy controls and 15 patients with chronic obstructive pulmonary disease (COPD). MSGs were normal in all controls except one and in 14/15 COPD patients. 43/58 asthmatics (74%) exhibited MSG abnormalities with T lymphocyte infiltration (57%), mast cell infiltration (64%), basement membrane thickening (64%) and endothelial cell changes (26%). Histological abnormalities were predominantly observed in nonallergic asthmatics. We propose that activated T lymphocytes, present in the bronchial mucosal lymphoid tissue in chronic asthma might migrate, colonize other glandular and mucosal sites, and so trigger at a distance, an airway-like inflammation.
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PMID:Airway-like inflammation of minor salivary glands in bronchial asthma. 761 85

Cytologic examination of bronchoalveolar lavage fluid (BALF), including phenotypic analysis of lymphocytes, was performed on 32 Standardbreds with poor race performance and endoscopic examination findings characteristic of inflammatory airway disease (IAD). Nucleated cell counts in BALF from IAD-affected horses were higher than those in control horses; the cytologic profile of BALF in affected horses included mixed inflammation, characterized by mild neutrophilia, lymphocytosis, and monocytosis. Eosinophil and mast cell counts were not higher in the IAD-affected group, compared with those in the control group; however, 4 IAD-affected horses had marked eosinophilia (24.7 +/- 4.8% SEM) in BALF. Phenotypic analysis of lymphocytes in BALF obtained from IAD-affected horses revealed a low proportion of CD4-positive cells and B cells, compared with those in the control group; these findings may have been representative of a greater proportion of non-B, non-T cells (null cells) in horses with IAD. The cytologic profile of BALF obtained from horses with IAD differed from that in horses affected with chronic obstructive pulmonary disease, suggesting that the pathogenesis of inflammation in horses with IAD may differ from that of chronic obstructive pulmonary disease.
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PMID:Cytologic evaluation of bronchoalveolar lavage fluid obtained from standardbred racehorses with inflammatory airway disease. 766 48

Chronic airways inflammation is one of the features of chronic obstructive pulmonary disease (COPD). We demonstrated previously that bronchiolar epithelium in COPD contains increased numbers of macrophages and mast cells. Transforming growth factor beta1 (TGF-beta1) may be involved in this influx because it has chemotactic activity for macrophages and mast cells. In this study, we examined expression patterns of TGF-beta1, TGF-beta receptors type I and II (TGF-betaRI and TGF-betaRII) by immunohistochemistry and mRNA in situ hybridization in peripheral lung tissue of 14 current or ex-smokers with COPD (FEV1 < 75%) and 14 without COPD (FEV1 > 84%). In both groups, TGF-beta1 and its receptors are present in airway and alveolar epithelial cells, airway and vascular smooth muscle cells, and tissue and alveolar CD68(+) cells (considered herein to be macrophages). In subjects with COPD, a semiquantitative analysis revealed approximately twofold higher levels of TGF-beta1 mRNA and protein in bronchiolar and alveolar epithelium (p < 0.02) as compared with subjects without COPD. With regard to bronchiolar epithelial cells, we found a significant correlation between TGF-beta1 mRNA and protein expression (r = 0.62; p < 0.002), and between the FEV1 of all subjects together and TGF-beta1 protein (r = -0.60; p < 0.0002) and mRNA (r = -0.67; p < 0. 002) levels. The epithelial expression of TGF-beta1 mRNA and TGF-beta1 protein correlates with the number of intraepithelial macrophages (both: r = 0.44; p < 0.03) whereas intraepithelial mast cell numbers correlate with epithelial TGF-beta1 mRNA expression. These data suggest a role for TGF-beta1 in recruiting macrophages into the airway epithelium in COPD.
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PMID:Transforming growth factor beta1 and recruitment of macrophages and mast cells in airways in chronic obstructive pulmonary disease. 984 91

Adenosine administration by inhalation elicits concentration-related bronchoconstriction in subjects with asthma and chronic obstructive pulmonary disease (COPD). The mechanisms of adenosine-induced bronchoconstriction appear to involve a selective interaction with activated mast cells with subsequent release of preformed and newly-formed mediators. Further evidence linking adenosine signalling to asthma and COPD comes from the finding that many cell types that play important roles in the exacerbation of these conditions express adenosine receptors and demonstrate relevant effects through stimulation of these receptors. Therefore, blockade of these receptors may be a valuable approach to the treatment of asthma and chronic obstructive pulmonary disease. Promising adenosine-receptor targets for novel therapeutics of asthma and chronic obstructive pulmonary disease have recently been identified in a number of inflammatory cell types, including mast cells, eosinophils, lymphocytes, neutrophils, and macrophages. The recent characterisation of the A2B receptors indicates the human lung mast cell as one of the most strategic cellular targets.
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PMID:Adenosine-receptor subtypes: their relevance to adenosine-mediated responses in asthma and chronic obstructive pulmonary disease. 1221 85

Adenosine, when given by inhalation, initiates the narrowing of airways in subjects with asthma or chronic obstructive pulmonary disease (COPD). The underlying mechanism of this narrowing appears to involve the stimulation of specific mast cell surface adenosine receptors with the subsequent release of mediators and contraction of airway smooth muscle. Although methacholine and histamine have become gold standards as bronchial provocants used to quantify bronchial hyperresponsiveness, the airways response to the indirect stimulus adenosine more closely reflects bronchial inflammation. This distinctive feature of adenosine could be exploited to enable superior diagnostic discrimination between asthma and COPD, allow better monitoring of disease activity and progression, and improve the individual adjustment of long-term asthma management with topical glucocorticosteroids. In this article, we review recent developments in this area of rapidly evolving clinical research, focusing on the putative role of adenosine as a mediator of airway inflammation and as a useful bronchoprovocant in several clinical and research applications.
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PMID:Research applications and implications of adenosine in diseased airways. 1291 50

Adenosine, an endogenous signaling nucleoside that modulates many physiological processes has been implicated in playing an ever increasingly important role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). All cells contain adenosine and adenine nucleotides and the cellular production of adenosine is greatly enhanced under conditions of local hypoxia as may occur in inflammatory conditions such as asthma and COPD. In 1983, it was first reported that inhaled adenosine causes dose-related bronchoconstriction in patients with both allergic and non-allergic asthma but not in healthy volunteers. This hyperresponsiveness was also reported in patients with COPD, with those patients who smoked exhibiting a significantly greater response. This bronchoconstrictor effect of adenosine is orchestrated through the stimulation of specific cell membrane receptors and involves an important inflammatory cell, the mast cell. There is substantial evidence which suggests that mast cell activation is central to this unique response to adenosine. Mast cell mediator release makes a significant contribution towards airflow obstruction and the consequent symptoms in patients with asthma. Over the last two decades, researchers have investigated the effect of mast cell inhibitors as well as mast cell mediator receptor antagonists and their role in attenuating the bronchoconstrictor response to inhaled adenosine 5'-monophosphate (AMP). Promising results have been shown using mast cell stabilizers, histamine H1 receptor antagonists, selective cysteinyl leukotriene-1 receptor antagonists and inhibitors of 5-lipoxygenase and cyclo-oxygenase. Through these findings, the mast cell has been recognized as being a critical inflammatory cell in the adenosine-induced response in patients with asthma and COPD. To date, four subtypes (A1, A2A, A2B, A3) of adenosine receptors have been cloned each with a unique pattern of tissue distribution and signal transduction. Activation of these receptors has pro- and anti-inflammatory consequences making the development of agonists and/or antagonists at these receptor sites a novel approach in the treatment of patients with asthma and COPD. This review highlights the importance of adenosine in the pathophysiology of asthma and COPD, the critical role of the mast cell and the potential to target the adenosine receptor subtype in patients with asthma and COPD. The complete characterization of these adenosine receptor subtypes in terms of their distribution in humans and the development of selective agonists and antagonists, holds the key to our complete understanding of the role of this important mediator in asthma and COPD.
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PMID:Targeting adenosine receptors: novel therapeutic targets in asthma and chronic obstructive pulmonary disease. 1472 64

Orazipone (OR-1384) and OR-1958 are novel anti-inflammatory sulfhydryl reactive compounds with potential applications in the treatment of chronic obstructive lung disease and colitis. Mast cells are potent immune system cells which can be found in abundant numbers in mucosa of lung and gut. We have studied whether the anti-inflammatory effect of these compounds could be mediated through inhibition of the function of mast cells and compared their effects with the glucocorticoid budesonide. Human mast cell line (HMC-1) cells were activated using a combination of a calcium ionophore and a phorbol ester and the production of cytokines was measured using ELISA assay. Tumour necrosis factor-alpha mRNA levels were assessed using a semiquantitative reverse transcriptase polymerase chain reaction assay. Histamine release was studied in rat peritoneal mast cells. Orazipone, OR-1958 and budesonide inhibited significantly and dose dependently tumour necrosis factor-alpha production in HMC-1 cells with IC50-values of 20, 10, and 0.25 microM, respectively. Polymerase chain reaction studies showed that OR-1958 attenuated the activation-induced increase of tumour necrosis factor-alpha mRNA in HMC-1 cells. OR-1958 and, to a lesser extent, orazipone inhibited dose dependently compound 48/80-induced histamine release from rat peritoneal mast cells in a reversible manner. In contrast, budesonide did not appreciably affect the histamine release. Both orazipone and OR-1958 inhibit efficiently mast cell functions and therefore could prove useful in the treatment of diseases associated with inappropriate mast cell activation.
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PMID:Novel sulfhydryl-reactive compounds orazipone and OR-1958 inhibit cytokine production and histamine release in rat and human mast cells. 1558 79


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