Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 aim of the present study was to determine whether the number of mast cells in lichenified lesions of atopic dermatitis (AD) have a relationship to familial background of atopic respiratory disease (ARD). We obtained biopsy specimens of lichenified lesions from 59 consecutive patients with AD. They included 35 AD patients who had a personal history of ARD, 9 AD patients without a personal history of ARD but with a family history of ARD, and 15 "pure" AD patients without a personal or a family history of ARD. From each biopsy specimen, 4 microns-thick paraffin-embedded sections and/or 1 micron-thick Epon-embedded sections were prepared, and stained with Giemsa's reagent. With both methods of preparation, the sections from AD patients with a personal history of ARD showed significantly greater mast cell number in lichenified lesions than the "pure" AD patients. It is suggested that the increase of mast cells often seen in AD lesions may be characteristic of a subgroup of AD patients who have a predisposition for ARD.
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PMID:Heterogeneous distribution of mast cells in lichenified lesions of atopic dermatitis. 267 62

Parainfluenza type 1 (Sendai) virus infection in young rats induces airway growth abnormalities associated with persistent pulmonary dysfunction and hyperresponsiveness. The objectives of this study were to compare virus-susceptible brown Norway (BN) rats and virus-resistant F344 rats and to determine which of several virus-induced structural abnormalities, including bronchiolar hypoplasia, alveolar dysplasia, bronchiolar mural fibrosis, and increases in bronchiolar mast cells, were associated with virus-induced increases in pulmonary resistance and hyperresponsiveness to methacholine. We also determined whether bronchiolar mural thickening and fibrosis may be caused by increased bronchiolar expression of cytokines such as TGF-beta 1 into airways. BN rats infected with virus developed increases in respiratory resistance and hyperresponsiveness that persisted for 28 to 65 d after inoculation. Functional abnormalities were most strongly associated with bronchiolar mural thickening and fibrosis as well as with recruitment of inflammatory cells, including macrophages, mast cells, lymphocytes, and eosinophils, into the bronchiolar wall. F344 rats were resistant to significant virus-induced alterations in bronchiolar airway wall thickness and mast cell increases as well as to pulmonary function abnormalities. BN rats had increase pulmonary mRNA levels of TGF-beta 1 at 10 and 14 d after viral inoculation as compared with F344 rats. BN rats also had greater numbers of bronchiolar macrophages expressing TGF-beta 1 protein that were localized in bronchiolar walls at 10, 14, and 30 d after inoculation. We conclude that recruitment and persistence of airway inflammatory cells and airway wall fibrosis may be important alterations induced by viral lower respiratory disease during early life that can lead to long-term airway dysfunction and hyperresponsiveness. Virus-induced airway fibrosis may be mediated in part by increased TGF-beta 1 gene expression by bronchiolar macrophages in genetically susceptible individuals.
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PMID:Parainfluenza virus-induced persistence of airway inflammation, fibrosis, and dysfunction associated with TGF-beta 1 expression in brown Norway rats. 897 Mar 78

Nasal mucosa is heavily exposed to inflammatory and allergic stimuli, rhinitis being the most common form of allergic respiratory disease. The nose is an easily accessible organ and a good model for the study of allergies as it makes it possible to monitor the effects of specific challenges as well as therapeutic interventions, namely specific immunotherapy (SIT). Injectable, nasal or sublingual SIT are useful therapeutic strategies in the management of allergic rhinitis patients. Monitoring the evolution of parameters such as clinical scores, nasal peak flow variation or drug requirements during SIT provides important information on its clinical efficacy. Laboratory measurement of tryptase and eosinophil cationic protein in the target organ after specific nasal provocation makes it possible to record changes in the release of mast cell and eosinophil mediators, thus providing objective evidence of the immunological efficacy of this therapy on these cell populations and providing data which eventually will contribute to a better understanding of the multiple mechanisms of action of allergen desensitization therapy.
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PMID:Nasal provocation and immunotherapy. 1058 95

Asthma is a common respiratory disorder. It can no longer be viewed as a reversible airway obstruction but should instead be considered primarily as an inflammatory illness that has bronchial hyperreactivity and bronchospasm as its result. There are several potential benefits as well as limitations of the currently available antiasthmatic agents such as anticholinergics, beta 2-selective agonists, methylxanthines, corticosteroids, or mast cell stabilizers. Recent trends in the design of new antiasthmatic agents include isozyme selective phosphodiesterase inhibitors, inhibitors of the biosynthesis of interleukin-4 and IL-4 antagonists, lipoxygenase and leukotriene inhibitors, thromboxane A2 receptor antagonists, potassium channel openers and monoclonal antibodies.
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PMID:Recent perspectives in the design of antiasthmatic agents. 1094 72

The underlying respiratory disease is activated by unknown mechanism and results in an intense infiltration of mast cells and eosinophils into the entire respiratory mucosa. These cells synthesize leukotrienes (LTs) at a very high rate and mast cells also release histamine and tryptase and synthesize PGD(2) a vasodilator and bronchoconstrictor. Furthermore, AERD patients under synthesize from arachidonic acid (AA) a peculiar product called lipoxins, which opposes inflammation generated by leukotrienes. Finally, cysLT1 receptors are over expressed and highly responsive to LTE(4), further augmenting the underlying inflammatory disease. This inflammatory condition is partly inhibited by synthesis of PGE(2) through COX-1. PGE(2) partially inhibits 5-lipogygenase conversion of AA to LTA(4) and blocks release of histamine and tryptase from mast cells. When COX-l is inhibited by ASA or NSAIDs, PGE(2) synthesis stops and an enormous release of histamine and synthesis of LTs occurs. The upper respiratory reaction is mediated by both histamine and LTs but the bronchospastic reaction is mediated by LTs. The systemic effects of flush, gastric pain and hives are mediated by histamine. Aspirin desensitization can not be explained by disappearance of LT synthesis since urine LTE(4) levels are still elevated at acute ASA desensitization. However, mast cell products such as histamine, tryptase and PGD(2) are no longer released or synthesized at acute desensitization. It is more likely that a diminution in number or function of cysLT receptors accounts for the diminished inflammatory response found in ASA desensitization.
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PMID:Pathogenesis of aspirin-exacerbated respiratory disease. 1266 97

Bovine respiratory syncytial virus (BRSV) infection is an important cause of outbreaks of respiratory disease among calves. This virus commonly induces mild to severe respiratory signs but, in a substantial proportion of cases, is also reported to be associated with paroxystic respiratory distress syndrome (PRDS). The pathogenesis of this 'malignant' clinical form has not been fully elucidated. The present study aimed at determining whether mast cell (MC) degranulation plays a role in the physiopathologic cascade leading to the PRDS. Paired serum samples were taken in herds during outbreaks of severe respiratory diseases (acute sera) and 3 weeks after (convalescent sera). Based on seroconversion to BRSV and clinical picture, 67 pairs of sera were selected from calves with a BRSV-associated PRDS for circulating MC tryptase determination. A MC metachromatic score was measured in post-mortem lungs from animals died from a BRSV-associated PRDS (principals) and compared with reference scores obtained from healthy lungs (controls). Levels of tryptase were significantly higher in acute sera (26.6 +/- 12.4 microg/l) compared to convalescent sera (8.4 +/- 7.8 microg/l; P<0.001). Metachromatic scores yielded significantly different results between controls and principals (P<0.01), demonstrating a significant disappearance of metachromatic granules from lung MCs in principals. Taken together, these data demonstrate the presence of an extensive MC degranulation in BRSV-associated PRDS.
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PMID:Extensive mast cell degranulation in bovine respiratory syncytial virus-associated paroxystic respiratory distress syndrome. 1474 Nov 32

Aspirin-sensitive respiratory disease (ASRD) is a condition characterized by persistent and often severe inflammation of the upper and lower respiratory tracts. Patients develop chronic eosinophilic rhinosinusitis, nasal polyposis, and asthma. The ingestion of aspirin and other cyclooxygenase-1 (COX-1) inhibitors induces exacerbations of airway disease that may be life-threatening. Thus, aspirin sensitivity is a phenotypic marker for the syndrome, yet nearly all affected individuals can be desensitized by the administration of graded doses of aspirin, leading to long-term clinical benefits. Patients with aspirin sensitivity are often able to tolerate selective COX-2 inhibitors. The pathogenesis of ASRD is underpinned by abnormalities in eicosanoid biosynthesis and eicosanoid receptor expression coupled with intense mast cell and eosinophilic infiltration of the entire respiratory tract. This review focuses on the molecular, cellular, and biochemical abnormalities characterizing ASRD and highlights unanswered questions in the literature and potential future areas of investigation.
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PMID:Aspirin-sensitive respiratory disease. 1957 83

Aspirin-exacerbated respiratory disease (AERD) is explained in part by over-expression of 5-lipoxygenase, leukotriene C4 synthase (LTC(4)S) and the cysteinyl leukotriene (CysLT) receptors (CysLT1 and 2), resulting in constitutive over-production of CysLTs and the hyperresponsiveness to CysLTs that occurs with aspirin ingestion. Increased levels of IL-4 have been found in the sinus mucosa and nasal polyps of AERD subjects. Previous studies demonstrated that IL-4 is primarily responsible for the upregulation of LTC4S by mast cells and the upregulation of CysLT1 and 2 receptors on many immune cell types. Prostaglandin E(2) (PGE(2)) acts to prevent CysLT secretion by inhibiting mast cell and eosinophil activation. PGE(2) concentrations are reduced in AERD reflecting diminished expression of cyclooxygenase (COX)-2. IL-4 can inhibit basal and stimulated expression of COX-2 and microsomal PGE synthase 1 leading to decreased capacity for PGE(2) secretion. Thus, IL-4 plays an important pathogenic role in generating the phenotype of AERD. This review will examine the evidence supporting this hypothesis and describe a model of how aspirin desensitization provides therapeutic benefit for AERD patients.
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PMID:Interleukin-4 in the Generation of the AERD Phenotype: Implications for Molecular Mechanisms Driving Therapeutic Benefit of Aspirin Desensitization. 2226 78

Aspirin exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis with nasal polyposis and aspirin hypersensitivity. The aspirin-induced bronchospasm is mediated by mast cell and eosinophilic inflammation. Recently, it has been reported that the expression of discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is up-regulated in lung cancers and is regulated by transcription factor AP-2 alpha (TFAP2A), a component of activator protein-2 (AP-2) that is known to regulate IL-8 production in human lung fibroblasts and epithelial cells. To investigate the associations between AERD and DCBLD2 polymorphisms, 12 common variants were genotyped in 163 AERD subjects and 429 aspirin tolerant asthma (ATA) controls. Among these variants, seven SNPs (rs1371687, rs7615856, rs828621, rs828618, rs828616, rs1062196, and rs8833) and one haplotype (DCBLD2-ht1) show associations with susceptibility to AERD. In further analysis, this study reveals significant associations between the SNPs or haplotypes and the percentage of forced expiratory volume in one second (FEV(1)) decline following aspirin challenge using multiple linear regression analysis. Furthermore, a non-synonymous SNP rs16840208 (Asp723Asn) shows a strong association with FEV(1) decline in AERD patients. Although further studies for the non-synonymous Asp723Asn variation are needed, our findings suggest that DCBLD2 could be related to FEV(1)-related phenotypes in asthmatics.
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PMID:Potential association of DCBLD2 polymorphisms with fall rates of FEV(1) by aspirin provocation in Korean asthmatics. 2246 95

Aspirin exacerbated respiratory disease (AERD) is a distinct clinical entity characterized by eosinophilic rhinosinusitis, asthma and often nasal polyposis. Exposure to aspirin or other nonsteroid anti-inflammatory drugs (NSAIDs) exacerbates bronchospasms with asthma and rhinitis. Disease progression suggests a skewing towards TH2 type cellular response along with moderate to severe eosinophil and mast cell infiltration. Alterations in upper and lower airway cellular milieu with abnormalities in eicosanoid metabolism and altered eicosanoid receptor expression are the key features underlying AERD pathogenesis. Dysregulation of arachidonic acid (AA) metabolism, notably reduced prostaglandin E2 (PGE2) synthesis compared to their aspirin tolerant counterpart and relatively increased PGD2 production, a TH2/eosinophil chemoattractant are reported in AERD. Underproduced PGE2 is metabolized by overexpression of 15 prostaglandin dehydrogenase (15-PGDH) to inactive products further reducing PGE2 at real time. This relives the inhibitory effect of PGE2 on 5-lipoxygenase (5-LOX) resulting in overproduction of cysteinyl leukotrienes (CysLTs). Diminished formation of CysLT antagonists called lipoxins (LXs) also augments CysLTs responsiveness. Occasional intake of NSAIDs favors even more 5-LOX product formation, further narrowing the bronchoconstrictive bottle neck, resulting in acute asthmatic exacerbations along with increased mucus production. This review focuses on abnormalities in biochemical and molecular mechanisms in eicosanoid biosynthesis, eicosanoid receptor dysregulation and associated polymorphisms with special reference to arachidonic acid metabolism in AERD.
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PMID:Biochemical pathogenesis of aspirin exacerbated respiratory disease (AERD). 2324 57


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