Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the phenotype and activation status of leukocytes in the bronchial mucosa in patients with isocyanate-induced asthma. Fiberoptic bronchial biopsy specimens were obtained from nine subjects with occupational (five toluene- and four methylene diisocyanate-sensitive) asthma, 10 subjects with extrinsic asthma, and 12 nonatopic healthy control subjects. Bronchial biopsy specimens were examined by immunohistology with a panel of monoclonal antibodies and the alkaline phosphatase-antialkaline phosphatase method. There was a significant increase in the number of CD25+ cells (interleukin-2 receptor-bearing cells, presumed "activated" T-lymphocytes; p less than 0.01) in isocyanate-induced asthma compared with that of control subjects. There were also significant increases in major basic protein (BMK-13)-positive (p less than 0.02) and EG2-positive (p less than 0.01) cells that represent total and "activated" eosinophil cationic protein-secreting eosinophils, respectively. In agreement with our previous findings, CD25+ (p less than 0.01), BMK-13 (p less than 0.03), and EG2+ (p less than 0.01) cells were also elevated in extrinsic asthma. No significant differences were observed in the numbers of T-lymphocyte phenotypic markers (CD3, CD4, and CD8) between subjects with asthma (isocyanate-induced and extrinsic) and control subjects. Similarly, no significant differences in immunostaining for neutrophil elastase (neutrophils) or CD68 (macrophages) were observed. The results suggest that isocyanate-induced occupational asthma and atopic (extrinsic) asthma have a similar pattern of inflammatory cell infiltrate. The results support the view that T-lymphocyte activation and eosinophil recruitment may be important in asthma of diverse etiology.
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PMID:Activated T-lymphocytes and eosinophils in the bronchial mucosa in isocyanate-induced asthma. 153 7

We have used immunohistochemistry and monoclonal antibodies to analyze the phenotypic composition and activation status of the cellular infiltrate of bronchial biopsies obtained by fiber optic bronchoscopy of 11 atopic asthmatic subjects (FEV1% predicted range 78 to 114), 9 atopic nonasthmatic control subjects, and 10 normal healthy subjects. Examination of mucosal biopsies obtained from both central (level I) and subsegmental (level II) bronchi showed that the highest number of CD45-, DC3-, DC4-, and CD8-positive cells were found in the group with asthma. There was a significant increase in the number of interleukin-2 receptor (CD25)-positive cells (a marker of lymphocyte activation) at airway level I in the asthmatic group compared with both nonasthmatic atopic (p less than 0.05) and normal control subjects (p less than 0.01). Eosinophil numbers were significantly increased in asthma at both airway levels and at airway level II in the nonasthmatic atopic group when compared with normal healthy control subjects (p less than 0.05). EG2-positive cells (an index of secretion of eosinophil cationic protein following activation) were found at both airway levels in the asthmatic group and at level I in the nonasthmatic atopic control group (p less than 0.05). When asthmatic subjects were compared with normal healthy subjects, there was a reduction in the number of neutrophil elastase-positive cells in the asthmatic subjects which, as a percentage of leukocytes, was significant (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma. 225 60

To determine whether adhesion molecules and cytokines are upregulated in the bronchial mucosa of chronic bronchitics, we obtained bronchial biopsies in 16 chronic bronchitics, in eight asymptomatic smokers, and in seven normal nonsmoking subjects. Bronchial biopsies were examined by immunohistochemistry to identify the expression of E-selectin and intercellular adhesion molecular-1 (ICAM-1) on vessels and on bronchial epithelium, and the expression of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), neutrophil elastase, and eosinophil cationic protein (EG-2) on cells in the submucosa. Chronic bronchitics had an increased number of E-selectin-positive vessels when compared with both asymptomatic smokers (p < 0.05) and normal subjects (p < 0.01). The numbers of ICAM-1-positive vessels, neutrophils, and IL-1 beta, TNF-alpha-, and EG-2-positive cells were not significantly different in the three groups of subjects examined. When the bronchitic group was divided according to the presence or absence of airway obstruction, the increased number of E-selectin-positive vessels persisted only in bronchitics with airway obstruction, who also had an increased expression of ICAM-1 on basal epithelial cells. We concluded that in the bronchial mucosa of chronic bronchitics with airway obstruction, there is an increased expression of E-selectin on vessels and of ICAM-1 on basal epithelial cells, suggesting the involvement of these adhesion molecules in the pathogenesis of the disease.
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PMID:Upregulation of adhesion molecules in the bronchial mucosa of subjects with chronic obstructive bronchitis. 750 5

Six patients with delayed pressure urticaria (DPU) applied clobetasol propionate (0.05%) ointment or its base to predetermined test sites on the right and left thigh as part of a randomized, double-blind study. A pressure challenge was administered to each test site at the initial visit and repeated after 3 days and 6 weeks of treatment and at between 4 and 8 weeks after treatment. The areas of pressure-induced weals were measured 6 h after each challenge. At the 6-week visit, a 4-mm punch biopsy was taken from pressure-challenged skin on each test site. Sections were stained for mast cells and immunohistochemical labelling was used to demonstrate neutrophils (neutrophil elastase), eosinophils (eosinophil cationic protein), monocytes/macrophages (EBM 11), cells expressing the beta-2 integrins (CD11/18) and the vascular adhesion molecules, E selectin and intercellular adhesion molecule-1 (ICAM-1). In the steroid-treated sites, there was a significant decrease (P < 0.05, Wilcoxon's matched-pairs test) in the size of the pressure weals compared with baseline at 3 days, 6 weeks and at follow-up. Demonstrable mast cells were significantly decreased (P = 0.059) in the pressure-challenged areas in the steroid-treated sites compared with the base-treated sites. The histological response to pressure was minimal in both sites perhaps demonstrating an active pharmacological effect of the ointment base. In conclusion, the application of potent topical steroids significantly reduced the clinical response to pressure in patients with DPU, possibly through a reduction in mast cells.
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PMID:The effects of topical corticosteroids on delayed pressure urticaria. 754 Nov 90

We hypothesized that repeated IgE-mediated late-phase reactions are critical in the pathogenesis of atopic dermatitis (AD). Prior studies have shown that extracellular deposition of eosinophil granule major basic protein (MBP) occurs in lesional AD skin, despite a paucity of infiltrating eosinophils, and that deposition of both neutrophil and eosinophil granule proteins occurs in the IgE-mediated late-phase reaction. We evaluated the participation of both eosinophil and neutrophil granule proteins in AD. Cutaneous biopsy specimens and serum and urine samples were obtained from 22 patients with AD. Lesional tissue was examined by means of immunofluorescence for neutrophil elastase and lactoferrin and for eosinophil granule MBP, eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP). Serum levels of elastase, MBP, EDN, and ECP and urine levels of MBP, EDN, and ECP were measured. Marked extracellular deposition of at least one of the eosinophil granule proteins was present in the dermis of 15 of the 22 AD skin specimens, but minimal or no extracellular neutrophil elastase or lactoferrin deposition was observed in any specimens. Serum and urine levels of MBP, EDN, and ECP in the patients were elevated when compared with those of normal controls, whereas serum levels of neutrophil elastase were not elevated. Serum MPB levels correlated with extent of body surface involvement. These results suggest that eosinophil degranulation occurs in AD but that neutrophil degranulation does not. Although eosinophil degranulation is prominent in both the late-phase reaction and in AD, the lack of neutrophil degranulation in AD demonstrates differences in the inflammatory reactions.
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PMID:Assessment of eosinophil and neutrophil participation in atopic dermatitis: comparison with the IgE-mediated late-phase reaction. 802 90

The causative relationship between airway inflammation and hyperreactivity is unclear, since inflammatory changes have been examined at one or, at most, a few time-points after antigen challenge in both human asthma and animal models. We have made a detailed investigation of inflammatory and functional changes in the airways up to 8 days after antigen challenge in guinea-pigs. In particular, we examined the hypothesis that eosinophil-derived mediators contribute to tissue damage and the development of airway hyperresponsiveness. Following antigen challenge, the influx of inflammatory cells and mediator release in airway tissue and bronchoalveolar lavage fluid were correlated temporally with histopathological changes in airway tissue and airway responsiveness. Eosinophil influx was demonstrable at 4 h. Eosinophilia peaked after 24 h and persisted for at least 8 days. Parallel increases in the concentrations of major basic protein and eosinophil cationic protein in bronchoalveolar lavage fluid indicated that the eosinophils were activated. Eosinophilia was accompanied by subepithelial oedema and epithelial damage co-localized with major basic protein immunoreactivity. A transient neutrophilia (< 48 h duration) and an increase in neutrophil elastase in bronchoalveolar lavage fluid peaked at 14 h. The proportion of airway macrophages with an activated morphology increased at 8 h and remained markedly elevated until 72 h. Airways were hyperresponsive to histamine at 4 h and for at least 8 days. The antigen-induced airway inflammation resemble in time-course and histopathology that seen in antigen-challenged asthmatics, and indicate that the eosinophil and its cytotoxic proteins may be major mediators of airway mucosal damage and airway hyperresponsiveness.
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PMID:Time-course of antigen-induced airway inflammation in the guinea-pig and its relationship to airway hyperresponsiveness. 880 59

Although Type I allergy is a trigger for provoking chronic inflammation, whether allergic sinusitis (AS) can be distinguished from sinusitis due to chronic infection is still debated. This study was performed to characterize inflammatory cells in AS and to determine whether patients with AS differ from patients with chronic suppurative sinusitis (CSS). 5 patients with AS and 10 patients with CSS were investigated. Cellular infiltration was studied using immunohistochemistry with monoclonal antibodies using CD3, CD4, CD8, CD25, major basic protein (BMK13), eosinophil cationic protein (EG2), neutrophil elastase, and tryptase. There were no differences in CD3+, CD4+, CD25+, and tryptase+ cells between the groups. Whereas the total number of eosinophils (BMK13+) also did not significantly differ, the number of activated eosinophils (EG2+) was significantly higher (P < 0.05) in patients with AS. Furthermore, a statistically significant increase in the percentage of activated eosinophils to total eosinophils (P < 0.05) was observed in patients with AS. In contrast, the number of neutrophil elastase+ cells was significantly higher (P < 0.05) in patients with CSS. These results suggest that patients with AS can be distinguished immunohistochemically from patients with CSS, with AS being distinguished by activated eosinophil infiltration.
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PMID:Preferential infiltration by activated eosinophils in allergic sinusitis. 925 57

Ketotifen is marketed throughout the world as an antiallergy drug, but whether it affects infiltration of inflammatory cells into airway mucosa is not known. We studied the effects of ketotifen on symptoms, pulmonary function, and airway inflammation in 25 patients with atopic asthma. Patients took ketotifen (1 mg twice daily) or a matching placebo for 8 weeks in a double-blind, parallel-group study. Data recorded on diary cards were used for 2 weeks before treatment began, and they were used for the last 2 weeks of treatment to study asthma symptoms, use of beta 2-agonists, and peak expiratory flow (PEF). Pulmonary function tests, bronchial responsiveness to methacholine, and fiberoptic bronchoscopy were performed before and after treatment. Biopsy specimens were obtained by bronchoscopy. Specimens were stained immunohistochemically with monoclonal antibodies against stored eosinophil cationic protein (EG1), the secreted form of eosinophil cationic protein (EG2), mast-cell tryptase (AA1), neutrophil elastase (NP57), CD3, CD4, CD8, and CD25. The numbers of positively stained cells in the lamina propria were counted. Compared with the placebo, the ketotifen-treated group exhibited significant improvement of asthma symptoms (P < 0.05) and bronchial responsiveness (P < 0.05). This was accompanied by a reduction of EG2+ eosinophils (P < 0.05), CD3+ T cells (P < 0.001), CD4+ T cells (P < 0.01), and CD25+ activated T cells (P < 0.01) in the bronchial mucosa. These results suggested that the beneficial effects of ketotifen in bronchial asthma may result from consequent inhibition of activated eosinophils and T-cell recruitment into the airway. Moreover, ketotifen may relieve allergic inflammation in bronchial asthma.
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PMID:Effects of ketotifen on symptoms and on bronchial mucosa in patients with atopic asthma. 928 80

Cellular events that occur in status asthmaticus (SA) remain poorly investigated. Autopsy studies frequently emphasized about the presence of eosinophils in bronchial airway wall, whereas recent studies reported increased number of neutrophils in patients dying of sudden-onset fatal asthma. Mucus plugs occluding the bronchial lumen are almost constant features during SA. Bronchial lavage (BL) may be useful to remove mucus plugs in cases of atelectasis and/or refractory SA. We investigated the contribution of different cell types and cellular mediators (neutrophil elastase, eosinophil cationic protein [ECP], histamine, interleukin-8 [IL-8]) to the pathogenesis of SA. We studied 16 BL from eight patients undergoing mechanical ventilation (MV) for SA (time interval from onset of MV = Day 0 to Day 11), four BL from patients undergoing MV without preexisting respiratory disease (V), 11 BL from patients with stable asthma (A) and eight BL from healthy controls (C). SA exhibited higher number and percentage of neutrophils (81.5 +/- 4.5%) than V (44.3 +/- 12.2) (p < 0.05), A (6.9 +/- 2.7) and C (9.5 +/- 3.8) (p < 0.0001), and higher number of eosinophils than V, A, and C (p < 0.01). Neutrophil elastase, ECP, and IL-8 levels were dramatically increased in SA. Histamine was higher in SA than in C and V (p < 0.05). Bronchial neutrophilia was not related to concomitant bacterial infection as bacteriological cultures were positive in only three BL. Eosinophils, mast cells and histamine were higher in BL performed within the first 48 h of MV (p < 0.05) than in BL performed later on. Our results indicate that bronchial inflammation in SA differs from bronchial inflammation in mild asthma. Persistent bronchial neutrophilia is associated with increased eosinophils and mast cells in the early phase of SA. Neutrophils may result in tissue damage and participate to the shedding of the epithelium in SA.
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PMID:Bronchial neutrophilia in patients with noninfectious status asthmaticus. 947 49

Toluene diisocyanate (TDI) is the most prevalent agent in occupational asthma (OA) in Korea. The immuno-pathologic mechanism for TDI-induced bronchoconstriction remains to be clarified. We studied the immunohistochemical finding of inflammatory cells in bronchial mucosa in subjects with TDI-induced asthma. Fiberoptic bronchial biopsy specimens were obtained from nine subjects with TDI-induced asthma. Six allergic asthma sensitive to house dust mite were enrolled as controls. Bronchial biopsy specimens were examined by immunohistology with a panel of monoclonal antibodies to mast cell tryptase (AA1), secretary form of eosinophil cationic protein (EG2), pan T-lymphocyte (CD3) and neutrophil elastase (NE). There was a significant increase in the number of AA1+, EG2+ and NE+ cells in TDI-induced asthma compared to those of allergic asthma (p=0.02, p=0.04, p=0.03, respectively). No significant differences were observed in the number of CD3+ cells (p=0.27). These findings support the view that neutrophil recruitment together with eosinophil and mast cell, may contribute to the bronchoconstriction induced by TDI.
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PMID:Immunohistochemical characterization of the cellular infiltrate in airway mucosa of toluene diisocyanate (TDI)-induced asthma: comparison with allergic asthma. 953 14


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