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)

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease caused by bronchial colonization with Aspergillus fumigatus that affects approximately 10% of patients with cystic fibrosis (CF). The diagnosis in CF patients is difficult because the cardinal symptoms of ABPA occur frequently in CF, ie, pulmonary infiltrates and wheezing, as well as the frequent colonization with A fumigatus that leads to humoral reactivity. If left untreated, ABPA leads to bronchiectasis and pulmonary fibrosis. The pathogenesis of ABPA seems to be a prolonged asthmatic late-phase reaction orchestrated by CD4+ Th2-like T cells in response to persistent pulmonary A fumigatus allergen exposure. Thus, polyclonal and A fumigatus-specific IgE antibodies (and IgA and IgG) and blood pulmonary eosinophilia are stimulated by Th2-derived cytokines such as IL-4 and IL-5. In addition, IL-4 would also promote pulmonary transendothelial migration of eosinophils, basophils, and lymphocytes via induction of cell adhesion molecules and their ligands. IgE mast cell interactions would also contribute to the bronchial reactivity and inflammation. Recent advances have begun to identify immunodominant A fumigatus allergens. Evaluation of the quantity of IgE antibodies (and IgA and IgG) and T-cell cytokine responses to specific A fumigatus allergens should aid in the diagnosis and immunopathogenesis of ABPA, especially in CF patients.
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PMID:Allergic bronchopulmonary mycosis complicating cystic fibrosis. 147 42

Systemic Sclerosis is a multisystemic disease characterized by sclerosis of the skin and visceral organs, vasculopathy (Raynaud's phenomenon) and autoantibodies. The criteria for the classification of the disease requires either proximal scleroderma (major criteria) or the presence of 2 of the 3 minor features namely sclerodactyly, digital pitting scars and bibasilar pulmonary fibrosis. There are 3 subsets of this condition--diffuse variant, limited variant (CREST syndrome) and Overlap Syndrome (where patients have features of other rheumatic diseases). There are localized forms of scleroderma and pseudoscleroderma states. The presenting features of Systemic Sclerosis are usually Raynaud's, skin changes and arthralgia. Systemic complaints like breathlessness, dyspepsia, etc depending on the organ involved may be present. Management starts with patient education regarding the disease, skin care, exercises and regular medical check-up. There is no miracle cure but much can be done to improve the quality of life of the patient. Nifedepine and other drugs may improve Raynaud's phenomenon. Drugs can be used to treat other complications. Various medication have been tested as disease modifying drugs for scleroderma. These include drugs which inhibit collagen like D-penicillamine, colchicine, and immunosupressive drugs like cyclosporin. Ketotifen, a mast cell stabilizer has been reported to be effective in scleroderma. As it is a relatively safe drug, clinical trials are underway.
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PMID:Systemic sclerosis. 162 Nov 27

As elevated bronchoalveolar lavage (BAL) fluid histamine levels are noted in patients with pulmonary fibrosis (PF), we assayed BAL fluid from 16 patients with PF for the presence of a histamine releasing factor (HRF). HRF activity was assayed by measuring release of the preformed mast cell-derived mediators, histamine, or beta-hexosaminidase (beta-hex) from a purified population of IL-3 dependent mouse bone marrow derived mast cells (MBMMC) or human blood basophils. Mean BAL cell free histamine levels in the patients with PF was 1226 +/- 1349 pg/ml, whereas BAL histamine levels in a comparison group of six non-PF patients was 118 +/- 60 pg/ml. HRF was significantly elevated in BAL fluid of patients with PF (mean beta-hex release 24.5 +/- 12.9%; range 6.8 to 52.4%) compared to the non-PF group of patients (mean beta-hex release 7.9 +/- 7.7%; range 1.8 to 20.7%). The PF HRF not only degranulated MBMMC, but also induced the generation of the arachidonic acid metabolite leukotriene C4 from MBMMC (24.6 +/- 4.2 ng leukotriene C4/10(6) MBMMC). The PF HRF did not appear to be a cytokine previously identified in BAL fluid of patients with PF (i.e., platelet derived growth factor or insulin growth factor-1) or a human cytokine able to degranulate human basophils (i.e., IL-1, or granulocyte-macrophage-CSF) as these recombinant human cytokines did not induce MBMMC beta-hex release. Physicochemical characterization of the HRF revealed that it was relatively heat stable, pronase sensitive and on Sephadex G-75 and G-200 column chromatography had an apparent molecular mass of 30 to 50 kDa. The ability of PF BAL to induce beta-hex release from MBMMC was not dependent on IgE as unsensitized or lactic acid treated MBMMC release similar amounts of beta-hex compared to MBMMC sensitized with IgE. Thus, BAL fluid of patients with PF contains an HRF that induces beta-hex release from MBMMC via an IgE-independent mechanism. The presence of the HRF could explain elevated BAL histamine levels in patients with PF.
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PMID:Mast cells and pulmonary fibrosis. Identification of a histamine releasing factor in bronchoalveolar lavage fluid. 169 11

It has been well known that the number of mast cells increases during the development of fibrosis in various tissues including the lung. However, the role of mast cells in fibrosis still remains obscure. In the present paper, we evidenced that pulmonary fibrosis could be induced in genetically mast cell-deficient WBB6F1-W/Wv mice as well as WBB6F1-(+/+) mice having mast cells normally by the treatment with bleomycin (BLM, 5 mg/kg, i.v., 10 days), and there was not much difference in the histological changes of lungs between the two strains. An increase in the hydroxyproline content of the lung of WBB6F1-W/Wv mice was rather higher than that of WBB6F1-(+/+) mice. Previously, we reported that tranilast, an antiallergic drug inhibiting chemical mediator release from mast cells, suppressed the development of BLM-induced pulmonary fibrosis in ICR mice, suggesting the possibility that mast cells play certain roles in fibrosis. However, it was evidenced in the present report that tranilast suppressed BLM-induced fibrosis in WBB6F1-W/Wv mice. Tranilast neither suppressed the cytotoxic activity of BLM against KB cells and L-929 cells in vitro, nor inhibited the antitumor activity of BLM against Sarcoma-180 transplanted subcutaneously into ICR mice. Tranilast may act through suppressing BLM-induced activation of lymphoid cells including macrophage and neutrophil. These results indicate an inconsequential role of mast cells in the development of fibrosis. Increases in the number of mast cells and in histamine content of the lung, which were widely reported in the lungs of BLM-treated mice, may be the result of fibrosis.
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PMID:Bleomycin-induced pulmonary fibrosis in genetically mast cell-deficient WBB6F1-W/Wv mice and mechanism of the suppressive effect of tranilast, an antiallergic drug inhibiting mediator release from mast cells, on fibrosis. 171 9

To study the nature and extent of mast cell heterogeneity within a single species, we have developed methodologies to isolate rat lung mast cells (LMC) and have compared these to peritoneal mast cells (PMC) and intestinal mucosal mast cells (IMMC). In normal and athymic nude (rnu/rnu) rats, a single intratracheal administration of bleomycin (5 U/kg) leads to pulmonary fibrosis accompanied by parenchymal hyperplasia of mast cells that are histochemically like PMC rather than IMMC. Using collagenase digestion of fibrotic rat lungs (30-80 days after bleomycin treatment), we recovered an average of 58.1 x 10(6) viable cells per rat, containing 2.5% mast cells. Control experiments in which PMC were subjected to the isolation procedure used for LMC showed that there was no qualitative effect on PMC, but that a reduction of 26-60% in responsiveness to secretagogues occurred. Isolated LMC secreted histamine in response to 48/80, A23187, substance P, VIP and somatostatin and bradykinin, but at lower levels than PMC. The anti-allergic compound theophylline, which does not inhibit antigen-induced histamine secretion by IMMC, was effective against both LMC and PMC. Taken together, the thymus independence of pulmonary mast cell hyperplasia, the histochemical characteristics and the responsiveness to secretagogues and anti-allergic compounds indicate that the majority of dispersed LMC are similar to PMC rather than to IMMC. Whether LMC should be considered analogous to PMC or, because of their size, histamine content and responsiveness to many secretagogues, intermediate between PMC and IMMC, remains to be determined through additional studies.
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PMID:Isolation and characterization of lung mast cells from rats with bleomycin-induced pulmonary fibrosis. 246 79

The purpose of this study was to determine if asbestos-induced pulmonary fibrosis in the rat can affect the levels of autacoids and peptides in freshly isolated lung cells. Lung fibrosis was experimentally induced in rats by a single intratracheal instillation of 5 mg UICC Canadian chrysotile B fibers. Isolated lung cells were prepared from normal and from asbestos-exposed rats. These cells were also fractionated on bovine serum albumin (BSA) gradients. The contents of serotonin (5-HT), histamine (HIST), vasoactive intestinal peptide (VIP), and bombesin (BN) were measured in isolated total cell preparations as well as in density-fractionated cell populations from normal and from asbestos-exposed rats. Analysis of total lung cell preparation showed the presence of heterogeneous populations in normal rat lung. After asbestos exposure, there were significant changes in these cell populations as evidenced by significant increases in lymphocyte and mast cell numbers. In addition, increased levels of 5-HT, HIST, and VIP were observed in isolated lung cells obtained from rats exposed to asbestos 1, 3, and 6 months after instillation. BN content was unchanged 3 months after treatment, but was significantly increased at the 6 month-interval, suggesting a different pattern of response for this neuropeptide. Density fractionation of various cell populations further showed selective changes in specific cell fractions of lung after asbestos exposure. At 6 months, increased levels of 5-HT, HIST, and VIP were associated with cell fraction 7, whereas changes in BN content were found in cell fractions 2 and 3. Similarly, there was a significant increase of mast cells in fraction 7 at the 6-month interval.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in autacoid and neuropeptide contents of lung cells in asbestos-induced pulmonary fibrosis. 288 13

Fibrotic lung tissue shows increased connective tissue deposition and fibroblast proliferation and in addition a substantial increase in mast cell numbers in and around the fibrotic area. To elucidate the question of whether products of mast cells affect the proliferative behaviour of structural cells in the lung and thereby contribute to fibrogenesis, the effect of histamine, a prominent mast cell derived mediator, on the in vitro proliferation of primary cultures of normal adult human lung fibroblasts was studied. Histamine enhanced fibroblast proliferation in a dose dependent manner, with an optimum effect at a physiological concentration of 10(-7) mol/l. This effect occurred when cells were exposed to histamine at restricted times during cell growth and was shown to depend in part on the stage of the cell cycle reached by the fibroblasts. The histamine induced proliferation was mediated through an H2 histamine receptor on the fibroblast, being inhibited by cimetidine, an H2 antagonist, and not by pyrilamine maleate, an antagonist of the H1 receptor. Mast cell products such as histamine may interact with and promote the increased fibroblast proliferation found in pulmonary fibrosis.
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PMID:Effect of histamine on proliferation of normal human adult lung fibroblasts. 321 52

Mast cells are critical for the expression of certain IgE-mediated responses, but the precise contributions of mast cells to biological processes not involving IgE are obscure. We have employed genetically mast cell-deficient WBB6F1-W/Wv and WCB6F1-S1/S1d mice to investigate the roles of mast cells in several different biological responses. This work strongly suggests that mast cells are not required for the elicitation of contact sensitivity (CS) responses, suppressor T cell-dependent tolerance to CS, reserpine-induced inhibition of CS responses, or bleomycin-induced pulmonary fibrosis. By contrast, mast cells appear to contribute to the acute gastric injury induced by ethanol and the acute inflammation of the skin induced by croton oil.
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PMID:Analysis of mast cell function in biological responses not involving IgE. 357 Apr 98

The distribution, density, and histochemical subtype of mast cells were studied in the respiratory tract of rats with bleomycin-induced pulmonary fibrosis. In normal rats, mast cell densities were highest in the trachea and lowest in the bronchus and parenchyma. Two histochemically distinct mast cell populations were identified in the mucosa adjacent to the tracheal cartilage, but elsewhere only a single population of typical connective tissuelike mast cells was found. After intratracheally administered bleomycin, lung histamine levels (micrograms/g wet weight) increased as much as 14-fold by Day 50. Pulmonary mast cell changes were present early in the fibrotic process, and by Day 14 the mast cell density in the parenchyma was 10 times normal. These parenchymal mast cells were histochemically of the connective tissue type. Thus, pronounced mast cell hyperplasia occurs during the evolution of experimental pulmonary fibrosis. This model provides a powerful tool to study pulmonary mast cells and to identify their role in fibrotic disease.
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PMID:Mast cell heterogeneity and hyperplasia in bleomycin-induced pulmonary fibrosis of rats. 620 34

Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.
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PMID:A new model of progressive pulmonary fibrosis in rats. 834 14


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