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)

Imiglucerase, the recombinantly produced enzyme, is gradually replacing the human placental derived alglucerase in the treatment of gaucher patients. We describe the first case, to the best of our knowledge, of an anaphylactoid reaction to imiglucerase in a patient who tolerated alglucerase. The patient was diagnosed at the age of 2 4/12 years with anemia and hepatosplenomegaly. Over the years he had suffered from marked splenomegaly, thrombocytopenia and recurrent bleeding episodes. At the age of 24 he started treatment with imiglucerase. After 3 months of treatment, immediately after starting an infusion, he experienced flushing, cough, tachycardia, palpitation, chest pain and excessive sweating, which reoccurred on a consecutive administration. Substitution with alglucerase was tolerated well, with only mild rash when he was premedicated with benadryl. Immediate skin tests to alglucerase, imiglucerase and gelatin were negative. IgG against alglucerase was undetectable. The in vitro mast cell degranulation test was positive for alglucerase, imiglucerase heamaccel (a gelatin based plasma substitute, which is a component of imiglucerase). This sensitivity to imiglucerase but not to alglucerase, raises the question of future treatment for this patient, since the production of alglucerase may cease, once imiglucerase production will cover the need for replacement enzyme.
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PMID:Anaphylactoid reaction to imiglucerase, but not to alglucerase, in a type I Gaucher patient. 1038 90

Mast cells and eosinophils may play a role in the pathophysiology of chronic cough in nonasthmatics. It is unknown, however, whether degranulation of these cells occurs in the airways of such patients. Thirty-five nonsmoking patients referred with a chronic nonproductive cough (mean cough duration 76.2 months) were evaluated using a comprehensive diagnostic protocol. Bronchoalveolar lavage (BAL) cell differentials and BAL histamine, tryptase and eosinophilic cationic protein (ECP) concentrations were determined. Ten nonsmoking healthy volunteers served as controls. Diagnostic subgroups were identified: eight postnasal drip syndrome (PNDS), seven cough variant asthma (CVA), seven gastro-esophageal reflux (GOR), seven dual aetiology and six idiopathic. Nonasthmatic coughers (NAC) were characterized as those patients without bronchial hyperresponsiveness on histamine challenge and whose cough had either responded to therapy for PNDS or GOR or failed to improve with antiasthma therapy. There was a significant increase in both eosinophil and mast cell numbers (p<0.05) and in histamine levels (p = 0.027) when NAC patients were compared with controls. Tryptase and ECP levels were elevated in 7 of 23 and 6 of 23 NAC patients, respectively. In conclusion, airway inflammatory cell numbers are not only increased but also activated, suggesting an important role for airways inflammation in the pathophysiology of chronic nonproductive cough.
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PMID:Bronchoalveolar lavage findings in patients with chronic nonproductive cough. 1083 24

Asthma is a condition characterized by variable airflow obstruction, airway hyper-responsiveness (AHR) and airway inflammation which is usually, but not invariably, eosinophilic. Current thoughts on the pathogenesis of asthma are focused on the idea that it is caused by an inappropriate response of the specific immune system to harmless antigens, particularly allergens such as cat dander and house dust mite, that result in Th2-mediated chronic inflammation. However, the relationship between inflammation and asthma is complex, with no good correlation between the severity of inflammation, at least as measured by the number of eosinophils, and the severity of asthma. In addition, there are a number of conditions, such as eosinophilic bronchitis and allergic rhinitis, in which there is a Th2-mediated inflammatory response, but no asthma, as measured by variable airflow obstruction or AHR. Bronchoconstriction can also occur without obvious airway inflammation, and neutrophilic inflammation can in some cases be associated with asthma. When we compared the immunopathology of eosinophilic bronchitis and asthma, the only difference we observed was that, in asthma, the airway smooth muscle (ASM) was infiltrated by mast cells, suggesting that airway obstruction and AHR are due to an ASM mast cell myositis. This observation emphasizes that the features that characterize asthma, as opposed to bronchitis, are due to abnormalities in smooth muscle responsiveness, which could be intrinsic or acquired, and that inflammation is only relevant in that it leads to these abnormalities. It also emphasizes the importance of micro-localization as an organizing principle in physiological responses to airway inflammation. Thus, if inflammation is localized to the epithelium and lamina propria, then the symptoms of bronchitis (cough and mucus hypersecretion) result, and it is only if the ASM is involved -- for reasons that remain to be established -- that asthma occurs.
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PMID:New insights into the relationship between airway inflammation and asthma. 1214 12

In a recent study, the difference between asthma and eosinophilic bronchitis (a condition characterized by cough but not airway hyperresponsiveness or airflow obstruction) was infiltration of airway smooth muscle (ASM) by mast cells. Mast cells produce a variety of lipid mediators, chemokines, cytokines, and enzymes that may interact with ASM cells to cause hyperreactivity to constrictive stimuli and proliferation, and activated ASM can produce stem cell factor and other chemokines, cytokines, and growth factors that may act in recruitment, differentiation, and retention of mast cells. Mast cell infiltration of the airways in asthma is T-cell-dependent, and TH2 cytokines from T cells and other sources act in mast cell expansion from circulating and tissue precursors. The recent data on interactions of mast cells and ASM suggest that this could be an important contributor to airway hyperresponsiveness in asthma. Why this occurs in asthma and how it is sustained remain to be established.
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PMID:The role of the mast cell in asthma: induction of airway hyperresponsiveness by interaction with smooth muscle? 1524 45

Poly(ADP-ribose) polymerase (PARP) plays an important role in tissue injury in conditions associated with oxidative stress and inflammation. Because asthma is a chronic inflammatory disorder of the airways, we designed the present experimental study to evaluate the effects of PARP inhibition on allergen-induced asthma-like reaction in ovalbumin-sensitized guinea pigs. Cough and dyspnea in response to ovalbumin aerosol were absent in naive guinea pigs, whereas they became severe in the sensitized animals. In the latter ones, ovalbumin aerosol also induced a rapid increase in PARP activity, bronchiolar constriction, pulmonary air space inflation, mast cell degranulation, poly(ADP-ribose) and nitrotyrosine immunostaining, myeloperoxidase activity, and malondialdehyde in lung tissue, as well as a rise in the amounts of nitrites and tumor necrosis factor-alpha in bronchoalveolar lavage fluid. Pretreatment with the PARP inhibitors 3-aminobenzamide (10 mg/kg b.wt.) or 5-aminoisoquinolinone (0.5 mg/kg b.wt.) given i.p. 3 h before ovalbumin challenge significantly reduced the severity of cough and the occurrence of dyspnea and delayed the onset of respiratory abnormalities. Both PARP inhibitors were also able to prevent the above morphological and biochemical changes of lung tissue or bronchoalveolar lavage fluid induced by ovalbumin challenge. Conversely, p-aminobenzoic acid, the inactive analog of 3-aminobenzamide, had no effects.
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PMID:Inhibition of poly(ADP-ribose) polymerase prevents allergen-induced asthma-like reaction in sensitized Guinea pigs. 1525 47

This study evaluates the effects of a copper amine oxidase (histaminase) purified from the pea seedling as a free or immobilized enzyme on asthmalike reactions to inhaled antigen in actively sensitized guinea pig in vivo. Male albino guinea pigs, sensitized with ovalbumin, were challenged with the antigen given by aerosol; free histaminase or CNBr-Sepharose immobilized histaminase was given intraperitoneally (20 microg, 3 or 24 h before antigen challenge) or by aerosol (4 microg, 30 min before or during ovalbumin aerosol). The following parameters were examined: latency time for the onset of respiratory abnormalities, cough severity score, and occurrence and duration of dyspnea. We also evaluated lung histopathology, mast cell degranulation, and lung myeloperoxidase and malonydialdehyde levels. Histaminase significantly reduced the severity of cough and the occurrence of dyspnea and delayed the onset of respiratory abnormalities. Both enzymes prevented bronchial constriction, pulmonary air space inflation, leukocyte infiltration (evaluated as myeloperoxidase activity), and lipoperoxidation of cell membranes (evaluated as malonyldialdehyde production). No relevant differences in pharmacological potency were noted between free or immobilized enzyme. This study provides evidence that histaminase counteracts acute allergic asthmalike reaction in actively sensitized guinea pigs, raising the possibility of new therapeutic strategies for allergic asthma in humans.
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PMID:Effect of a plant histaminase on asthmalike reaction induced by inhaled antigen in sensitized guinea pig. 1547 52

Cough variant asthma and the closely related corticosteroid responsive cough syndromes eosinophilic bronchitis and atopic cough are common causes of chronic cough. The diagnosis is often not overt but detailed investigation of airway responsiveness and airway inflammation can be helpful. Cough variant asthma, eosinophilic bronchitis and atopic cough are all associated with eosinophilic airway inflammation, which is similar to that seen in non-cough predominant asthma. However, evidence of activated mast cells and increased concentrations of mast cell products appears to be confined to the conditions associated with cough, suggesting a role for mast cell degranulation in the superficial airway structures in the pathogenesis of cough. Cough variant asthma is typically corticosteroid responsive; leukotriene antagonists and antihistamines also help. Further study of this interesting asthma variant may increase our understanding of the relationship between airway inflammation and airway dysfunction.
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PMID:Cough and asthma. 1556 83

Most studies agree that post-nasal drip syndrome (PNDS), asthma, gastroesophageal reflux disease (GORD), and laryngopharyngeal reflux (LPR) are the commonest causes of chronic cough in the immunocompetent, non-smoking patient who is not taking an angiotensin-converting enzyme inhibitor. No diagnostic test has been found to define those who are said to have PNDS other than a response to a first-generation antihistamine. Examining the available evidence suggests that mechanical stimulation of the pharynx by mucus is not an adequate theory for the production of cough. Inflammatory mediators in the lower airways are raised in PNDS, cough variant asthma and GORD, and the theory that an inflammatory process is affecting 'one airway' is a plausible one. Nasal disease is more likely to result in cough from the co-existing involvement of the lower airways through an as yet undefined pathway, and eosinophil and mast cell mediation appear a likely mechanism.
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PMID:The aetiology of chronic cough: a review of current theories for the otorhinolaryngologist. 1648 May 51

In this study, we have evaluated the effects of the polyphenol epigallocatechin-3-gallate (EGCG), an antioxidant molecule that also enhances constitutive nitric-oxide synthase (NOS) activity, on antigen-induced asthma-like reaction in sensitized guinea pigs. For comparison, we used epicatechin, which shares antioxidant but not NOS-modulating properties with EGCG. Ovalbumin-sensitized guinea pigs placed in a respiratory chamber were challenged with ovalbumin. EGCG (25 mg/kg b.wt.) or epicatechin (25 mg/kg b.wt.) was given i.p. 20 min before ovalbumin challenge. We analyzed latency time for the onset of respiratory abnormalities, cough severity, duration of dyspnea, lung tissue histopathology, mast cell activation (by granule release), leukocyte/eosinophilic infiltration (by major basic protein and myeloperoxidase), oxygen free radical-mediated injury (by nitrotyrosine and 8-hydroxy-2-deoxyguanosine and superoxide dismutase), NOS activity, and bronchial inflammatory response [by tumor necrosis factor-alpha in bronchoalveolar lavage (BAL)]. In the sensitized animals, severe respiratory abnormalities appeared soon after the antigen challenge, accompanied by bronchoconstriction, alveolar inflation, and a marked increase in the assayed parameters of inflammatory cell recruitment, free radical lung injury, and release of proinflammatory molecules in BAL fluid. This was associated with marked depression of constitutive NOS activity. Pretreatment with EGCG, but not epicatechin, significantly reduced all the above parameters and sustained endothelial-type NOS activity. These findings provide evidence that EGCG, probably by modulating NOS activity, can counteract allergic asthma-like reaction in sensitized guinea pigs and suggest its possible future use for the treatment of asthma.
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PMID:Epigallocatechin-3-gallate reduces allergen-induced asthma-like reaction in sensitized guinea pigs. 1652 38

Schisandra fructus has been used for treatment of cough and thirst in Korea. However, its therapeutic mechanisms remain largely unclear. To investigate the biological effect of Schisandra fructus water extract (SFWE), we examined the effect of SFWE on the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-induced pro-inflammatory cytokine secretion in the human mast cell line HMC-1. HMC-1 cells were stimulated with PMA plus A23187 in the presence or absence of SFWE. Tumor necrosis factor (TNF)-alpha, interleukin 6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF) productions were measured by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction. Inhibitory IkappaB/nuclear factor-kappaB (NF-kappaB) expression was assessed by western blot. SFWE suppressed PMA plus A23187-induced TNF-alpha, IL-6, and GM-CSF production in dose-dependent manners. Furthermore, SFWE inhibited IkappaB degradation and NF-kappaB nuclear translocation. These results suggest that SFWE inhibits the secretion of pro-inflammatory cytokines in HMC-1 cells through blockade of IkappaB degradation and NF-kappaB activation. Taken together, these findings may help elucidate the mechanism of action of this medicine in the modulation of mast cell activation in inflammatory conditions.
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PMID:Effects of the Schisandra fructus water extract on cytokine release from a human mast cell line. 1720 33


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