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: EC:6.2.1.7 (BAL)
1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors report the case of a worker in the hard metal industry presenting with asthma due to cobalt and nickel. The diagnosis was supported by the history, positive skin tests and lymphocyte activation as well as elevated levels of the metals in the urine and BAL. Challenge led to a delayed asthmatic reaction occurring 3.5 to 24 hours after exposure. The BAL contained high levels of tungsten and cobalt, the level of the latter doubling 48 hours after exposure. After the provocation test a nasal and broncho-alveolar eosinophilia was observed. The possibility of a delayed hypersensitivity reaction to metals is discussed by the authors.
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PMID:[Occupational asthma due to hard metals hypersensitivity]. 1216 93

Interleukin (IL)-17 is produced by activated memory CD4(+) cells and induces cytokines and chemokines that stimulate neutrophil generation and recruitment. Here, we investigated the involvement of IL-17 in the bronchial influx of neutrophils in experimental allergic asthma. Inhalation of nebulized ovalbumin (OVA) by sensitized mice with bronchial eosinophilic inflammation resulting from chronic OVA exposure induced early IL-17 mRNA expression in inflamed lung tissue, concomitant with a prominent bronchial neutrophilic influx. Anti-IL-17 monoclonal antibodies (mAb) injected before allergen inhalation strongly reduced bronchial neutrophilic influx, in a manner equally as potent as the anti-inflammatory dexamethasone. Remarkably, anti-IL-17 mAb significantly enhanced IL-5 levels in both BAL fluid and serum, and aggravated allergen-induced bronchial eosinophilia. In another series of experiments, anti-IL-17 mAb were given repeatedly during the inhalatory challenge phase with OVA of sensitized mice. This treatment regimen abated bronchial neutrophilia in parallel with reduction of bone marrow and blood neutrophilia. In addition, anti-IL-17 mAb treatment elevated eosinophil counts in the bone marrow and bronchial IL-5 production, without alteration of allergen-induced bronchial hyperresponsiveness. In summary, our results demonstrate that IL-17 expression in airways is upregulated upon allergen inhalation, and constitutes the link between allergen-induced T cell activation and neutrophilic influx. Because neutrophils may be important in airway remodeling in chronic severe asthma, targeting IL-17 may hold therapeutic potential in human asthma.
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PMID:Interleukin-17 orchestrates the granulocyte influx into airways after allergen inhalation in a mouse model of allergic asthma. 1249 27

This case, in a 23-year-old man presenting with cough, sputum, dyspnea on effort and wheezing, had been diagnosed as bronchial asthma at another hospital. Because inhaled steroid and theophylline were far from effective, he was admitted to our hospital for further evaluation. A blood test revealed marked eosinophilia. Chest radiography showed diffuse, small nodular shadows in both lung fields, and a chest CT scan demonstrated diffuse centrilobular nodules and thickening of the bronchi and bronchioles. A spirometric test showed obstructive and restrictive ventilatory impairment, but the depressed forced vital capacity failed to show improvement in response to bronchodilator inhalation, discouraging a diagnosis of asthma. Eosinophilic lung disease with prominent eosinophilic bronchiolitis was diagnosed on the basis of BAL eosinophilia and thoracoscopic lung biopsy findings. The symptoms and blood eosinophilia were responsive to administration of oral prednisolone (30 mg daily); radiographic and CT findings also showed improvement. This case showed a marked similarity to the recently reported "eosinophilic bronchiolitis", and was probably not a type of bronchial asthma.
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PMID:[A case of eosinophilic lung disease presenting asthma-like symptoms and centrilobular shadows in both lung fields]. 1458 93

During the preclinical study of new therapeutic modality, we evaluate whether the treatment can reverse the established asthma phenotypes in animal model. However, few have reported on the long term persistence of asthma phenotypes upon re-challenge with allergen (secondary challenge) in animal model. We evaluated the persistence of asthma phenotypes by secondary challenge at different times in previously challenged murine asthma model. BALB/c mice sensitized by intraperitoneal injections of 20 micro g of ovalbumin and 1 mg of alum on days 1 and 14 were challenged initially by the inhalation of 1% ovalbumin for 30 min on days 21, 22, and 23. Each group of mice was rechallenged at 5, 7, 9, or 12 weeks after the initial challenge. Airway hyperresponsiveness, BAL fluid, airway histology and serum ovalbumin-specific IgE level were evaluated. Airway eosinophilia, airway inflammation and serum ovalbumin-specific IgE production persisted upon secondary allergen challenges at least 12 weeks after the initial challenge. However, airway hyperresponsiveness persisted only until mice were rechallenged 7 weeks after the initial challenge. Airway inflammation and allergen specific IgE production may persist longer than airway hyperresponsiveness in a mouse asthma model of secondary allergen challenge.
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PMID:Airway inflammation and allergen specific IgE production may persist longer than airway hyperresponsiveness in mice. 1496 44

Airway hyperresponsiveness, airway eosinophilia and increased IgE levels in serum are the important characteristic features of asthma. We evaluated the potential of para-Bromophenacyl bromide (PBPB), a known phospholipase A(2) inhibitor, on allergen-induced airway hyperresponsiveness in a mouse model. We sensitized and challenged mice with ovalbumin (OVA) to develop airway hyperresponsiveness as assessed by airway constriction and airway hyperreactivity (AHR) to methacholine (MCh) induced by allergen. The mice were orally treated with PBPB (0.1, 1 and 10 mg/kg) during or after OVA-sensitization and OVA-challenge to evaluate its protective or reversal effect on airway constriction and AHR to MCh. Determination of OVA-induced airway constriction and AHR to MCh were performed by measuring specific airway conductance (SGaw) using non-invasive dual-chamber whole body-plethysmography. We observed that PBPB (1 mg/kg) significantly reduced OVA-induced airway constriction and AHR to MCh (p<0.01). PBPB (1 mg/kg) treatment significantly inhibited PLA(2) activity in the BAL fluid. Cytokine analysis of the BAL fluid revealed that PBPB caused an increase in interferon-gamma (IFN-gamma) (p<0.02) and a decrease in interleukin-4 (IL-4) (p<0.05) and interleukin-5 (IL-5) (p<0.05) levels. The OVA-specific serum IgE levels (p<0.01) and the BAL eosinophils (p<0.001) were also reduced significantly. Thus, PBPB is capable of modulating allergen induced cytokine levels and serum IgE levels, and alleviating allergen induced airway hyperresponsiveness and eosinophils in mice. These data suggest that PBPB could be useful in the development of novel agents for the treatment of allergen induced airway hyperresponsiveness.
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PMID:Para-Bromophenacyl bromide alleviates airway hyperresponsiveness and modulates cytokines, IgE and eosinophil levels in ovalbumin-sensitized and -challenged mice. 1545 21

IL-13 is a mediator of allergen-induced airway hyperresponsiveness (AHR). The aim of this study was to evaluate whether eotaxin and IL-5 were implicated in the effects of IL-13 on allergen-induced AHR or whether IL-13 may exert its effects through direct actions on airway smooth muscle (ASM). To study this question airway inflammation and AHR were induced in mice by sensitization and subsequent challenge on three successive days with ovalbumin. A monoclonal anti-IL-13 antibody administered before each challenge significantly reduced AHR without affecting airway eosinophilia. No changes of mRNA in BAL and lung tissues or protein levels in BAL of IL-5 or eotaxin were found following anti-IL-13 treatment. Combined injection of monoclonal anti-IL-5 and antieotaxin antibodies before each antigen challenge blocked airway eosinophilia but failed to reduce AHR. IL-13 induced calcium transients in cultured murine ASM cells and augmented the calcium and contractile responses of these cells to leukotriene D4. These results suggest that IL-13 plays an important role in allergen-induced AHR and is important in the early phases of the inflammatory process. Its effects on AHR are mediated independently of IL-5 and eotaxin and may involve a direct effect on ASM to augment its responsiveness.
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PMID:IL-13 may mediate allergen-induced hyperresponsiveness independently of IL-5 or eotaxin by effects on airway smooth muscle. 1556 87

The effects of an intravenous injection of Sephadex beads on lung eosinophil infiltration and eosinophil peroxydase activity and its relationship to bronchial hyperresponsiveness was examined in guinea pigs. This Sephadex beads injection led to blood, lung and airway eosinophilia in association with bronchial hyperresponsiveness. Histologic examination of the lower bronchus indicated that the eosinophil number increased markedly in the mucosa and submucosa. In addition, the eosinophils surrounding the bronchioles 1 day after the Sephadex injection migrated further in airway submucosa and mucosa 7 and 14 days after. Moreover, the bronchial hyperresponsiveness is observed without histologic evidence of airway epithelium damage. Therefore, the bronchial hyperresponsiveness seems to be more related to the eosinophil infiltration in the airway epithelium and possibly eosinophil activation rather than to the eosinophil number recovered in the BAL fluid. We conclude that the maintenance of hyperresponsiveness state could be associated with the persistence of blood and airway eosinophilia.
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PMID:Role of airway eosinophilia and eosinophil activation in Sephadex-induced inflammation. 1567 61

In subjects not developing allergy, inhalation of nonpathogenic protein antigens causes no harm and is associated with tolerance induction. Repeated exposure to aerosolized ovalbumin (OVA) likewise does not evoke airway inflammation and induces inhalation tolerance in experimental animals. The present study explored the role of the inhibitory T-cell receptor CTLA-4, in preventing inflammation and in establishing inhalation tolerance in response to a protein antigen. Naive BALB/c mice were injected intraperitoneally with anti-CTLA-4 monoclonal antibody or control immunoglobulin G (IgG) and exposed daily to aerosolized saline or OVA over 10 or 20 consecutive days. OVA-specific IgE levels and the inflammatory response in airway tissues were assessed 2 days after last exposure. The OVA-specific IgE response was also evaluated in mice subjected to a subsequent immunogenic OVA challenge 18 days after last aerosol exposure. Additional mice were made tolerant by 10 days of OVA aerosol exposure and were then subjected to an immunogenic OVA challenge combined with CTLA-4 blockade or control IgG treatment. Repeated inhalation of aerosolized OVA alone did not cause a pulmonary inflammatory response. In contrast, 10 days of OVA exposure combined with blockade of CTLA-4 led to development of eosinophilic lung infiltrates, BAL fluid eosinophilia, goblet cell hyperplasia and increased OVA-specific IgE. By 20 days of OVA exposure and blockade of CTLA-4, the inflammatory response remained. Mice exposed to aerosolized OVA for 10 days exhibited greatly reduced OVA-specific IgE responses to subsequent immunogenic OVA challenge. Blockade of CTLA-4 during the period of OVA aerosol exposure did not prevent this suppression of the OVA-specific IgE response. Neither did blockade of CTLA-4 during immunogenic OVA challenge alter the allergen-specific IgE response. Our results indicate that in vivo blockade of CTLA-4 modulates the initial immune response to a protein antigen allowing the development of allergen-induced airway inflammation in naive mice. However, this initial exaggerated immune response is followed by the induction of inhalation tolerance, demonstrating that CTLA-4 signalling is not decisive in this process. Our findings also show that once inhalation tolerance is established it may not be disrupted by blockade of CTLA-4.
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PMID:Blockade of CTLA-4 promotes airway inflammation in naive mice exposed to aerosolized allergen but fails to prevent inhalation tolerance. 1630 40

The aim of this work was to characterize lung function and cellular responses in a large animal model for chronic asthma. All sheep were sensitized to house dust mite (HDM) by subcutaneous injection of HDM before lung challenges. Groups of sheep were given weekly lung challenges with either HDM (n = 12) or saline (control, n = 5) for 3 months. Post challenge, there were significant increases in lung resistance in 7 out of 12 HDM-challenged sheep, compared to control sheep. In HDM-responding sheep, there was a progressive increase in the magnitude of HDM-induced resistance throughout the trial. All HDM-challenged sheep developed BAL eosinophilia and bronchial hyperresponsiveness. In conclusion, sheep chronically challenged intralung with HDM consistently develop airway hyperresponsiveness and eosinophilia, whereas allergen-specific bronchoconstriction is observed in just over half of these sheep.
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PMID:Chronic airway disease: deteriorating pulmonary function in sheep associated with repeated challenges of house dust mite. 1706 Jan 75

Invariant NK T cells (iNKT) bridge the innate and adaptive immune response, being characterized by the ability to use invariant T cell receptors to recognize glycolipid antigens presented by CD1d, leading to an explosive cytokine effector response. As such it has been proposed that iNKT cells perform important roles as both effector and regulatory cells in a wide range of disease settings. These roles have been characterized in experiments depending on the use of iNKT-null mice, due to lack of either CD1d expression or Jalpha18 and the use of CD1d tetramers loaded with the model glycolipid antigen, alpha-galactosylceramide (alphaGalCer). Several studies have examined lung disease, infectious and allergic, in humans and mice. While the lung itself does not carry an exceptionally large population of iNKT cells (compared with, say, the liver), it does appear to be a site at which these cells can exert a profound effect. Several models of bacterial, fungal and viral murine lung infection have been investigated that have sometimes produced conflicting results. Abrogation of iNKT cell function in knockouts is often associated with disease exacerbation, indicating a regulatory role in lung infection. Studies in murine asthma models and in patients have similarly probed the role of iNKT cells in these settings. While there are again somewhat contradictory findings, evidence suggests a likely role for iNKT cells in mediating airway hyper-responsiveness (AHR), but probably not in Th2 polarization or lung eosinophilia. In marginally different models, administration of alphaGalCer has either ameliorated or exacerbated AHR. Different studies of BAL from human asthma patients show variously that there is either a very enlarged population of iNKT cells in the asthmatic lung, or that there is no significant difference from controls. Taken together, there are some observations that argue compellingly for an important role of iNKT cells in the lung, but resolution of some of the contradictory findings may await the development of reagents capable of providing alternative readouts of iNKT activation in these diverse disease settings.
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PMID:The role of natural killer T cells in lung inflammation. 1816 53


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