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:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Viral respiratory infections exacerbate asthma in many patients. We hypothesized that one mechanism by which this effect occurs may include potentiated or altered mediator release by mast cells and/or basophils to favor the development of late-phase asthmatic reaction (LAR). Therefore, we studied eight subjects with allergic rhinitis before and during an experimentally induced rhinovirus 16 (RV16) infection. We determined levels of plasma histamine and tryptase, and we observed the associated patterns of airway obstruction that developed following inhaled antigen challenge. Bronchial responsiveness to histamine, methacholine, and antigen were all significantly increased during the RV16 illness. Further, the incidence of LAR was significantly higher (five of eight) during the infection than before (one of eight; p = 0.014). In addition, in those patients whose pattern of response following antigen challenge converted from an immediate response only before infection to a dual response (immediate + late phase) during infection, plasma histamine concentrations after challenge were significantly greater than in those whose pattern of response did not change. We conclude that one mechanism by which RV16 infection increases the likelihood of LAR could include enhanced mediator release from pulmonary mast cells or from circulating or recruited basophils.
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PMID:Experimental rhinovirus 16 infection potentiates histamine release after antigen bronchoprovocation in allergic subjects. 172 Jun 1

Segmental antigen bronchoprovocation was used to define the nature of the inflammatory process in allergic airway disease. Bronchoalveolar lavage fluid obtained from allergic rhinitis patients 12 min after segmental antigen instillation (immediate response) revealed a significant increase in histamine and tryptase, but no cellular response. Repeat segmental lavage 48 h later (late response) showed marked and significant increases in both low and normal density eosinophils as well as striking elevations of eosinophil granular protein levels (major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein, and eosinophil peroxidase). Leukotriene C4, but not tryptase, concentrations were also consistently elevated in late lavage samples. Further, the late lavage samples showed a significant increase in interleukin-5 concentrations that correlated with the presence of eosinophils and eosinophil granular proteins. Neither eosinophils nor soluble mediators of eosinophils increased when normal subjects were similarly challenged with antigen. These data suggest that eosinophils are attracted to the airway during the late-phase allergic reaction and that IL-5 may produce changes in airway eosinophil density and promote the release of granular proteins to cause airway injury.
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PMID:Immediate and late airway response of allergic rhinitis patients to segmental antigen challenge. Characterization of eosinophil and mast cell mediators. 174 38

The activation of mast cells is generally considered to be an important trigger mechanism in the immediate allergic response. This study focused on the determination of three markers of mast cell activation after an allergen challenge. Nasal allergen challenges were performed in 25 subjects with seasonal allergic rhinitis using three allergen doses increasing in 10-fold steps in a standardised nasal lavage model for the subsequent recovery of the markers of mast cell activation. The levels of histamine and tryptase in the nasal lavage fluid were determined using radioimmunoassays, while the TAME-esterase activity was determined using a radiochemical technique. The nasal symptoms obtained on challenge were assessed using a scoring technique. The allergen challenge resulted in significant increases in the levels of all three markers, tryptase, histamine and TAME-esterase. In the individual measurements after the challenges there was a highly significant correlation between the TAME-esterase levels and the tryptase levels (r = 0.71; P less than 0.001), while the generation of histamine and tryptase was not significantly correlated. When comparing the cumulative generation of the three markers, significant correlations were found between all three. Allergen challenges in six non-allergic controls using the same technique did not result in any increase in tryptase levels. The findings suggest that the determination of tryptase in nasal lavage fluid may be a valuable indicator of mast cell activation in the upper airways.
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PMID:Tryptase in nasal lavage fluid after local allergen challenge. Relationship to histamine levels and TAME-esterase activity. 195 95

Bronchoalveolar lavage (BAL) fluid was evaluated for histamine and tryptase levels in 61 samples (46 samples from 24 atopic asthmatics, seven samples from seven patients with allergic rhinitis, and eight samples from eight normal volunteers). Asthmatics and patients with allergic rhinitis had significantly higher BAL histamine than did normal subjects (169 +/- 22, 141 +/- 23, 42 +/- 6 pg/ml, respectively; p less than 0.05, both comparisons). BAL fluid tryptase levels were also higher in asthmatics and patients with allergic rhinitis than in normal subjects (0.36 +/- 0.03, 0.38 +/- 0.05, 0.23 +/- 0.04 ng/ml, respectively; p less than 0.05, both comparisons); however, levels of tryptase and histamine in BAL were not correlated (r = -0.03 in the group as a whole, r = -0.12 in the asthmatic group). BAL concentration of histamine correlated inversely with FEV1 percent predicted in the asthmatic group (r = -0.44, p less than 0.005). Asthmatics with high BAL fluid histamine (greater than or equal to 100 pg/ml, n = 23) had lower FEV1 percent predicted (80 +/- 3% versus 96 +/- 3%, p = 0.0005), lower FEV1/FVC ratio (72 +/- 1% versus 77 +/- 2%, p less than 0.05), higher percentage of BAL eosinophils (2.2 +/- 0.4% versus 0.6 +/- 0.1%, p less than 0.002), and greater airway responsiveness (lower PD20 [13.1 +/- 3.4 versus 41.5 +/- 13.7 cumulative breath units, p less than 0.05]) compared with asthmatics with low BAL fluid histamine (less than 100 pg/ml, n = 23).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elevated bronchoalveolar lavage fluid histamine levels in allergic asthmatics are associated with increased airway obstruction. 206 43

To examine mast cell involvement in allergic rhinitis, levels of tryptase, a specific marker for mast cell activation, and histamine, a marker of mast cell and basophil activation, were measured in nasal-lavage fluid after nasal-allergen challenge. Twelve atopic subjects with allergic rhinitis and five nonatopic subjects were challenged with timothy grass or ragweed pollen at increasing doses of allergen. Tryptase and histamine levels were determined by an ELISA and radioenzyme assay, respectively; clinical responses were measured by assessment of sneezing, rhinorrhea, nasal congestion, and ocular tearing or itching. A positive clinical response was observed in seven of the atopic subjects and in none of the nonatopic subjects. Tryptase levels increased at least sevenfold higher than baseline levels in 100% of the atopic clinical responders and reached a maximum at the same dose of allergen where clinical symptoms were maximal. In contrast, histamine levels were only threefold or greater elevated in five of seven atopic clinical responders at this dose of allergen. (Histamine levels were lower in one subject and were only 50% higher in another subject than the corresponding baseline value.) Histamine levels and symptom scores were maximal at the same dose of allergen in only four of seven clinical responders. Overlap of peak mediator levels in subjects without a clinical response with those of the clinical responders occurred only in the case of histamine. Tryptase levels in nasal-lavage fluid appear promising as a useful indicator of allergic reactions and indicate that mast cell activation is the major factor in the immediate nasal-allergic response.
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PMID:Tryptase levels in nasal-lavage fluid as an indicator of the immediate allergic response. 304 43

The regulation of human IgE production in vitro by soluble T cell factors was examined. T cells were isolated from the peripheral blood of 2 patients with the hyper-IgE syndrome on the basis of their expression of Fc receptors for human IgE (Fc epsilon R). The T cells were incubated with human myeloma IgE (10 micrograms/ml), washed, reacted with immunosorbent-purified goat anti-human IgE conjugated with fluorescein isothiocyanate, and then separated into Fc epsilon R+ and Fc epsilon R- T cells on the fluorescence-activated cell sorter. Fc epsilon R+ T cells and Fc epsilon R- T cells were propagated in culture using supernatants of phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMC) and irradiated autologous PBMC. Supernatants of Fc epsilon R+ T cell lines but not of Fc epsilon R- T cell lines selectively enhanced IgE synthesis in cultures of B cells obtained from patients with allergic rhinitis but not from normal nonallergic subjects. The surface phenotype of the Fc epsilon R+ T cell line was predominantly T3+, T4+, Ia+ with few (15%) T8+ cells. Two T cell clones were grown from the Fc epsilon R+ T cell line by limiting dilution (0.3 cells/well). These clones possessed the T4+ helper/inducer phenotype and secreted IgE-enhancing factor(s). The IgE-enhancing factor(s) which had affinity for insolubilized human IgE was sensitive to treatment with trypsin and neuraminidase, and had as its target an IgE-bearing B cell. These results suggest that a subset of human T cells bearing an Fc epsilon R secretes an IgE-binding glycoprotein which selectively enhances IgE synthesis by IgE-bearing B cells.
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PMID:Production of IgE-potentiating factor in man by T cell lines bearing Fc receptors for IgE. 623 18

Late-phase reactions that occur in response to local antigen challenge have been demonstrated in the skin, nose, and lungs of humans. Late-phase reactions in these organs involve many mechanisms important in diseases such as atopic dermatitis, allergic rhinitis, and asthma. For this discussion, late-phase reaction research involving the skin model will be presented. Past research focused on the inflammatory components of late-phase reactions, but results were confounded by abrasion-related nonspecific inflammatory changes. Newer, less traumatic skin test methods have clarified the involvement of humoral and cellular elements in cutaneous late-phase reactions and demonstrated the efficacy of agents commonly used to treat allergenic conditions. Antigen challenge triggers the local release of histamine, prostaglandin D2, leukotriene C4, and tryptase. Dermal infiltrate abounds with eosinophils, basophils, neutrophils, and mononuclear cells several hours after challenge. Several investigators have shown that soluble proinflammatory cytokines are produced by cells at the antigen challenged site. Several of these cytokines may activate eosinophils and basophils, which release mediators of inflammation. Some of the newer nonsedating antihistamines appear to possess anti-inflammatory properties that may be unrelated to histamine antagonism and that might alter late inflammatory events of allergic disease.
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PMID:Pathogenesis and pharmacologic modulation of the cutaneous late-phase reaction. 750 36

Allergic rhinitis is the sixth most prevalent chronic health condition in the United States. To study the pathogenesis of the allergic response, we have used a model of nasal provocation with antigen. During the initial reaction of an allergic subject to allergen provocation, increases occur in the levels of histamine, tryptase, and prostaglandin D2. This pattern of mediator release, combined with histologic evidence of mast-cell degranulation, strongly supports the role of the mast cell in the acute allergic reaction. The response to antigen, however, does not end with mast-cell degranulation. Hours after challenge we observed the spontaneous recurrence of symptoms and increased responsiveness to antigenic and nonantigenic stimuli. Our central hypothesis is that cellular infiltration and activation after antigen challenge are responsible for the observed increase in nasal reactivity. The predominant cells in nasal lavage 24 hours after challenge are eosinophils and neutrophils, whereas the predominant cell in the mucosa is the CD4+ lymphocyte. An early step in the movement of cells from the peripheral blood involves adhesion between circulating leukocytes and the endothelium. Evidence suggests that vascular endothelial adhesion molecule may be responsible in part for the selective adherence of eosinophils to the endothelium.
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PMID:Observations on the response of the nasal mucosa to allergens. 752 55

Allergic mucosal inflammation is characterized by tissue infiltration with eosinophils, and associated activation of mast cells and T lymphocytes. Tumour necrosis factor (TNF) alpha/cachectin is a candidate cytokine relevant to the pathogenesis of these events through its capacity to upregulate the expression of endothelial cell adhesion molecules, mediate granulocyte chemoattraction, and activate eosinophils, mast cells and T cells. To investigate the presence and localization of TNF alpha in the nasal mucosa in allergic rhinitis, nasal biopsies from perennial rhinitic (n = 13) and non-rhinitic volunteers (n = 11) were embedded in glycol methacrylate and immunostained with a monoclonal antibody directed against TNF alpha, and adjacent 2 microns sections stained for tryptase, CD3 and eosinophil cationic protein. This identified positive immunostaining for TNF alpha in the submucosa of both the rhinitic and normal subjects (median cell counts 13 and 23 cells/mm2 respectively, P = 0.24) with cellular localization to mast cells but not to T-lymphocytes or eosinophils. In a subsequent study of seven atopic subjects, nasal allergen challenge produced increases in lavage levels of histamine and albumin, which was associated with significant release of TNF alpha as early as 2 min post-allergen when compared with the saline control day (P = 0.05). This difference was also apparent when studying the area under the curve both at 30 and 60 min post-challenge t-test (P = 0.015 and 0.02 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:TNF alpha is localized to nasal mucosal mast cells and is released in acute allergic rhinitis. 755 43

Human mast cells can be divided into two distinct phenotypes based on their content of neutral serine proteases, suggesting that they serve differing biologic and pathologic roles. Recently, it has been demonstrated that human mast cells are a source of several pleiotropic cytokines including IL-4, IL-5, IL-6, IL-8, and TNF-alpha, but not all mast cells contain all of these cytokines, suggesting that there is also functional heterogeneity with respect to cytokine expression. In this study, we have examined the relationship between mast cell neutral protease expression and cytokine content using immunohistochemistry. Bronchial mucosal biopsies from five normal subjects and five patients with allergic asthma, and nasal mucosal biopsies from five normal subjects and three patients with allergic rhinitis were embedded in glycol methacrylate. Sections (2 microns) were stained for IL-4, IL-5, and IL-6, adjacent to serial sections stained for tryptase and chymase. The distribution of cytokines among the tryptase+ chymase- mast cells (MCT) and tryptase+ chymase+ mast cells (MCTC) was examined by co-localization of cytokines to MCTC or MCT in serial sections using the camera-lucida. Although IL-4 was distributed among both mast cell phenotypes, it was expressed preferentially by the MCTC subset (overall 85% MCTC:15% MCT). In contrast, IL-5 and IL-6 were restricted almost exclusively to the MCT subset. Immunostaining of isolated skin mast cells (> 99% MCTC) supported these findings, with strong immunoreactivity present for IL-4 but very little for IL-5 or IL-6. These results indicate that in addition to exhibiting heterogeneity with respect to neutral protease content of the secretory granules, human mast cells are also heterogeneous with respect to cytokine content. This suggests that the biologic functions of MCTC and MCT cells differ as a result of their capacity to generate and release different cytokine profiles.
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PMID:Heterogeneity of human mast cells based on cytokine content. 760 7


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