Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Tryptases”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed2006

Effects of a reversible beta-tryptase and trypsin inhibitor (RWJ-58643) on nasal allergic responses.

BACKGROUND: beta-Tryptase is a multifunctional mast cell serine protease released during mast cell degranulation and tryptase/trypsin inhibitors are a novel potential therapeutic approach for allergic inflammatory diseases. OBJECTIVES: This study was performed to assess the effects of RWJ-58643 on nasal symptoms, eosinophil influx, and cytokine and chemokine release following nasal allergen challenge (NAC). METHODS: Male patients with grass pollen allergic rhinitis (n=16) out of season received single doses of RWJ-58643 (100, 300, 600 microg) or matched placebo given 30 min before NAC in a double-blind, randomized crossover design. A single dose of 200 microg budesonide was studied in an open-label extension phase. NAC was performed with Timothy grass pollen (ALK) via a nasal device, and nasal lavage was performed at times 0 (pre-drug, pre-allergen), 0.5 (30 min post-drug, pre-NAC) 1.5, 2.5, 4.5, 6.5, 8.5, and 24 h after drug administration. Nasal lavage mediators were analysed using a sensitive multiplexed bead immunoassay system. RESULTS: Low-dose RWJ-58643 (100 microg) and budesonide (200 microg) significantly reduced symptoms, eosinophils and levels of IL-5 following NAC. However, higher doses of RWJ-58643 (300 and 600 microg) caused a late eosinophilia and preceding increases in IL-5 compared with placebo. CONCLUSIONS: This study suggests that combined beta-tryptase and trypsin inhibition has therapeutic potential in allergic inflammation, however, this property is dose responsive and higher doses are ineffective and may cause eosinophilia.

Administration, Intranasal↗
PubMed2003

Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pig submucosal neurons.

Mast cells that are in close proximity to autonomic and enteric nerves release several mediators that cause neuronal hyperexcitability. This study examined whether mast cell tryptase evokes acute and long-term hyperexcitability in submucosal neurons from the guinea-pig ileum by activating proteinase-activated receptor 2 (PAR2) on these neurons. We detected the expression of PAR2 in the submucosal plexus using RT-PCR. Most submucosal neurons displayed PAR2 immunoreactivity, including those colocalizing VIP. Brief (minutes) application of selective PAR2 agonists, including trypsin, the activating peptide SL-NH2 and mast cell tryptase, evoked depolarizations of the submucosal neurons, as measured with intracellular recording techniques. The membrane potential returned to resting values following washout of agonists, but most neurons were hyperexcitable for the duration of recordings (> 30 min-hours) and exhibited an increased input resistance and amplitude of fast EPSPs. Trypsin, in the presence of soybean trypsin inhibitor, and the reverse sequence of the activating peptide (LR-NH2) had no effect on neuronal membrane potential or long-term excitability. Degranulation of mast cells in the presence of antagonists of established excitatory mast cell mediators (histamine, 5-HT, prostaglandins) also caused depolarization, and following washout of antigen, long-term excitation was observed. Mast cell degranulation resulted in the release of proteases, which desensitized neurons to other agonists of PAR2. Our results suggest that proteases from degranulated mast cells cleave PAR2 on submucosal neurons to cause acute and long-term hyperexcitability. This signalling pathway between immune cells and neurons is a previously unrecognized mechanism that could contribute to chronic alterations in visceral function.

Animals↗
PubMed1995

Tryptase and IgE concentrations in the respiratory tract of infants with acute bronchiolitis.

It has been proposed that a specific IgE response contributes to the immunopathology of acute respiratory syncytial virus (RSV) bronchiolitis but previous work has been difficult to replicate. Indirect evidence that might support this contention was sought by measuring total IgE concentrations in bronchoalveolar lavage (BAL) samples obtained from intubated infants and by attempting to detect mRNA for IgE in cells obtained from both the upper and lower respiratory tract. Evidence of significant mast cell activation was sought by measuring tryptase concentrations in BAL fluid and serum. Detectable concentrations of IgE were found in two of seven BAL samples obtained more than five days after intubation and mRNA for IgE was demonstrated in three of six BAL samples and three of six samples obtained from the upper respiratory tract. Tryptase was detectable in 11 of 12 BAL samples with the two highest values detected on day 1. These values were raised compared with control samples but were not such to suggest that mast cell degranulation is the major contributor to the inflammatory process. These results suggest that IgE may be produced in the airways of infants in response to RSV infection. The relationships between IgE production, RSV infection, and symptoms of acute bronchiolitis remain obscure.

Acute Disease↗
PubMed1998

Ethanol-induced urticaria: elevated tryptase levels after double-blind, placebo-controlled challenge.

We present a 48-year-old patient who complained for 1 year about urticarial reactions which appeared always when he ingested alcoholic beverages. Skin prick tests with ethanol were negative but positive with 10% acetic acid in the patient. Normal controls tested negative with acetic acid. Skin prick tests to common immediate-type allergens were negative. The patient underwent a double-blind, placebo-controlled challenge test. A few minutes after challenge with ethanol but not with placebo, the patient developed erythema and wheals on the chest and the upper arms. The tryptase serum level rose from undetectable (0.1 U/ml) before challenge to 3.8 U/ml after skin lesions had appeared. This case demonstrates that increased tryptase serum levels can help in the diagnosis of ethanol-induced urticaria.

Alcoholic Beverages↗
PubMed2006

Inhibitory effect of quercetin on tryptase and MCP-1 chemokine release, and histidine decarboxylase mRNA transcription by human mast cell-1 cell line.

Mast cells are important in reactions of allergic disease and are also involved in a variety of neuroinflammatory diseases. Mast cells can be immunologically activated by IgE through their Fc receptors, as well as by neuropeptides and cytokines to secrete mediators. Here we used a human mast cell-1 (HMC-1) cell line cultured and treated with a physiological activator, anti-IgE, and a nonphysiological activator, calcium ionophore A23187, for tryptase and MCP-1 generation and transcription of histidine decarboxylase. We used quercetin, a potent antioxidant, cytoprotective and anti-inflammatory compound capable of inhibiting histamine and some cytokines released from several cell types, as an inhibitor of immunological and nonimmunological stimulus for mast cells. In this study quercetin inhibits, in a dose-response manner, tryptase and MCP-1. Moreover, using RT-PCR quercetin inhibited the transcription of histidine decarboxylase, the rate-limiting enzyme responsible for the generation of histamine from histidine, and MCP-1. Our data suggest that quercetin is an important and good candidate for reducing the release of pro-inflammatory mast cell mediators activated by physiological and nonphysiological stimulators.

Antioxidants↗
PubMed1994

Histamine, tryptase, norepinephrine, angiotensinogen, angiotensin-converting enzyme, angiotensin I and II in plasma of patients with hymenoptera venom anaphylaxis.

Markers of immediate-type hypersensitivity such as histamine and tryptase were measured in the plasma of nonallergic volunteers and patients with a history of hymenoptera venom anaphylaxis. No significant differences in histamine or tryptase were found between patients and controls. Norepinephrine, an important compound involved in the control of cardiovascular functions and blood pressure, was the same in patients and nonallergic volunteers. In addition, components of the renin-angiotensin system were determined. Patients with hymenoptera venom anaphylaxis showed significantly lower plasma angiotensinogen concentrations as compared to healthy nonallergic controls (p < 0.007), whereas plasma ACE activity was the same. Likewise, the plasma levels of angiotensin I and angiotensin II were significantly reduced in patients as compared to controls (p < 0.04 and p < 0.003, respectively). These findings suggest that the renin-angiotensin system may play an important role as a counteracting factor in hymenoptera venom anaphylaxis.

Adult↗
PubMedDate not supplied

GM-CSF downregulates expression of tryptase, Fc epsilon RI and histamine in HMC-1 mast cells.

Fibroblast-derived growth factors like SCF are able to upregulate the expression of mast cell characteristics in human multilineage hematopoietic progenitor cells. Other factors, like GM-CSF, have been reported to inhibit this process, probably by the competitive recruitment of cells not belonging to the mast cell lineage. In this study, we investigated the influence of GM-CSF on immature mast cells of the HMC-1 cell line which already show low-level expression of mast cell tryptase, histamine and Fc epsilonRI alpha. Culture of HMC-1 cells with mast-cell-conditioning medium, containing fibroblast supernatants, upregulated tryptase activity, histamine contents and expression of Fc epsilonRI alpha. However, addition of GM-CSF (10 ng/ml) markedly downregulated these mast cell markers, without affecting proliferation and viability of cells. Thus, GM-CSF may provide an inhibitory signal during mast cell differentiation and probably even downregulates mast cell characteristics in more differentiated cells.

Cells, Cultured↗
PubMed2005

Mast cell tryptase in mast cell granules enhances MCP-1 and interleukin-8 production in human endothelial cells.

OBJECTIVE: Recent studies have highlighted the pathogenetic importance of chronic inflammation in cardiovascular disorders such as congestive heart failure and atherosclerosis. Mast cells release a wide variety of immune mediators that may initiate inflammatory responses, whereas endothelial cells (ECs) play a prominent role in the pathogenesis of cardiovascular diseases by secreting cytokines. The purpose of this study was to clarify the role of mast cells as an activator of ECs. METHODS AND RESULTS: ECs harvested from human umbilical cord veins were stimulated with mast cell granules (MCGs) prepared from sonicated human leukemic mast cells. The supernatants and total RNA from cells were collected. Levels of interleukin (IL)-1beta, tumor necrosis factor-alpha, and granulocyte colony-stimulating factor remained unchanged up to 24 hours. In contrast, levels of monocyte chemoattractant protein-1 (MCP-1) and IL-8 increased significantly within 6 hours. Northern blot analysis revealed an increase in MCP-1 and IL-8 mRNA expression in MCG-treated ECs. Induction of these chemokines was attenuated by antitryptase neutralizing antibody. Furthermore, MCP-1 and IL-8 were induced in ECs by incubation with human mast cell tryptase, but not with chymase. CONCLUSIONS: These results indicate that the production of MCP-1 and IL-8 in ECs was induced by MCG and amplified by tryptase.

Cells, Cultured↗
PubMed1994

Mast cells of two types differing in neutral protease composition in the human aortic intima. Demonstration of tryptase- and tryptase/chymase-containing mast cells in normal intimas, fatty streaks, and the shoulder region of atheromas.

Biochemical studies in vitro have demonstrated that stimulated mast cells induce macrophage foam cell formation through the synergistic action of mast cell granule neutral proteases and proteoglycans. To determine the presence and number of mast cells in human arterial intima, the site of atherogenesis, specimens of normal and atherosclerotic human aortic intima from 35 autopsies of persons ranging from 13 to 67 years old were stained with monoclonal antibodies against the two major proteases of mast cells, tryptase and chymase. All mast cells present were found to contain tryptase, and an average of 40% contained chymase as well. In sections of normal intimas, fatty streaks, and atheromas, the mast cells had average densities of 15/mm2, 15/mm2, and 3/mm2, respectively. In contrast to the normal intimas and fatty streaks, however, the atheromas had mast cells distributed unevenly in a typical pattern: 8/mm2 in the shoulder region, 1/mm2 in the fibrous cap, and none in the core region. In normal intimas, fatty streaks, and the shoulder region of atheromas, the mast cells amounted to 3% of all nucleated cells. The ratios of mast cells to T lymphocytes and to macrophages, respectively, were 2:1 and 1:4 in normal intimas, 1:3 and 1:10 in fatty streaks, and 1:5 and 1:20 in the shoulder region of atheromas. Thus, among the blood-borne cells in the human aortic intima, mast cells compose a significant cell population, and in terms of their protease content, these intimal mast cells are heterogeneous.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Tryptase inhibitors block allergen-induced airway and inflammatory responses in allergic sheep.

Tryptase, a mast cell serine protease, has been implicated in the pathophysiology of allergic asthma, but formal evidence to support this hypothesis has been limited by the lack of specific inhibitors for use in vivo. Therefore, in this study we examined the effects of two inhibitors of tryptase, APC 366 [N-(1-hydroxy-2-naphthoyl)-L-arginyl-L-prolinamide hydrochloride] and BABIM [bis(5-amidino-2-benzimidazolyl)methane] on antigen-induced early and late responses, airway responsiveness as measured by carbachol provocation, microvascular permeability as measured by bronchoalveolar lavage (BAL) albumin concentrations, and tissue eosinophilia from biopsies in allergic sheep. APC 366 and BABIM were administered by aerosol in all experiments. In vehicle control trials, antigen challenge resulted in peak early and late increases in specific lung resistance (SRL) of (mean +/- SE, n = 6) 259 +/- 30% and 183 +/- 27% over baseline, respectively. Treatment with APC 366 (9 mg/3 ml H2O given 0.5 h before, 4 h after, and 24 h after antigen challenge) slightly reduced the peak early response (194 +/- 41%), but significantly inhibited the late response (38 +/- 6%, p < 0.05 versus control trials). Twenty-four hours after challenge, APC 366 also completely blocked the antigen-induced airway hyperresponsiveness to inhaled carbachol observed in the control trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1996

Prednisolone treatment in asthma. Reduction in the numbers of eosinophils, T cells, tryptase-only positive mast cells, and modulation of IL-4, IL-5, and interferon-gamma cytokine gene expression within the bronchial mucosa.

We have tested the hypothesis that the beneficial effects of corticosteroids in asthma may result from reduction in the number of inflammatory cells infiltrating the bronchial mucosa with inhibition of cytokine gene expression. A randomized parallel group study was performed in 18 moderately severe asthmatic patients in whom an elective trial of corticosteroid treatment was indicated. Fiberoptic bronchoscopy was performed and bronchial biopsies taken from segmental carinae before and after 2 wk treatment with prednisolone (0.6 mg/kg/d) or matched placebo tablets. Immunohistology was performed on 6-microns cryostat sections using monoclonal antibodies. The number of cells expressing cytokine messenger RNA (mRNA) was assessed by in situ hybridization using S35-labeled riboprobes. When prednisolone- and placebo-treated groups were compared there was a decrease in airway methacholine responsiveness (p < 0.01) and an increase in FEV1 (p < 0.05) after prednisolone. This was accompanied by a reduction in CD3+ T lymphocytes (p < 0.05), "activated" EG2+ eosinophils (p < 0.02), and tryptase-only (mucosal-type) MCT cells (p < 0.02) but not MCTC (tryptase+chymase positive) cells in prednisolone-treated patients. In prednisolone-treated patients there was also a reduction in the number of cells expressing mRNA for interleukin-4 (IL-4, p < 0.01), and interleukin-5 (IL-5, p < 0.03) and an increase in cells expressing mRNA for interferon-gamma (IFN-gamma) (p < 0.01). These results support the view that corticosteroid treatment in asthma may act by modulation of cytokine expression with consequent inhibition of the local bronchial inflammatory infiltrate and tissue eosinophilia.

Adult↗
PubMed2003

Gene expression of cardiac mast cell chymase and tryptase in a murine model of heart failure caused by viral myocarditis.

This study examined the gene expression of mouse mast cell proteases to clarify their role in the pathophysiology of viral myocarditis. Male DBA/2 mice were inoculated intraperitoneally with the encephalomyocarditis virus and the gene expression of mast cell chymase, mouse mast cell protease (mMCP)-4 and -5, and tryptase, mMCP-6, matrix metalloproteinase (MMP)-9 and type-I procollagen was measured by real-time quantitative RT-PCR analysis. The gene expression of mMCP-4, -5 and -6 mRNA was increased at 5 days, and continued to increase to day 14, coinciding with a prominent inflammatory reaction and extensive myocardial necrosis and fibrosis. The gene expression of MMP-9 was also increased, and there was a significant correlation between upregulation of mast cell proteases and MMP-9. The gene expression of type-I procollagen was increased at 5 days and continued to increase to day 14, suggesting that a fibrotic process had already begun during the acute stage of viral myocarditis. These findings suggest that mast cell chymase and tryptase participate in the acute inflammation and remodeling process of viral myocarditis.

Animals↗
PubMed2003

Quantitative analysis of tryptase- and chymase-containing mast cells in eosinophilic conditions of cats.

The presence and density of tryptase-positive/chymase-positive mast cells (MCs) (MC(TC)), chymase-positive/tryptase-negative MCs (MCC), and tryptase-positive/chymase-negative MCs (MC(T)) in lesional skin from cats with eosinophilic conditions were investigated. Skin biopsy specimens from eight cats with eosinophilic plaque (three cats), eosinophilic granuloma (two cats), and eosinophilic dermatitis (three cats) were studied. Toluidine blue staining and a double-enzyme-immunohistochemical staining technique were performed to determine MC density and MC subtypes, respectively. MC density varied from 170.3 to 503 cells/mm2 (mean value of 314.9 cells/mm2). In the superficial dermis, 5.9% of the MC belonged to the MC(T), 12.8% to the MC(C), and 81.2% to the MC(TC) subtype. In the deep dermis, 12.8% belonged to the MC(T), 12.8% to the MC(C), and 73.8% to the MC(TC) subtype. It is the first time that MC(C) have been identified. The double-labeling procedure proved to be a reliable tool for identifying simultaneously the presence of MC subtypes in feline skin.

Animals↗
PubMed1993

Comparative histochemical and biochemical studies of mast cell tryptase in human gingiva.

Tryptase-like activity has previously been identified biochemically in gingival homogenates and gingival crevicular fluid (GCF) using substrates linked to the 7-amino-4-trifluoromethyl coumarin (AFC) leaving group. In the present study, activity was demonstrated histochemically in tissue sections with analogous 4-methoxy-2-naphthylamide (MNA) substrates. Z-Ala-Ala-Lys-MNA and D-Val-Leu-Arg-MNA were the most sensitive substrates. Comparison of staining patterns with the MNA substrates and toluidine blue indicated that enzyme activity was localized to mast cell secretory granules. Most stained cells were in the lamina propria, but a few were in the epithelium. The number of stained cells was somewhat greater in inflamed tissue from chronic periodontitis patients than in healthy tissue from controls. However, hardly any staining was seen in inflamed granulomatous tissue. Using high-salt buffer containing heparin, it was possible to extract enzyme activity from tissue sections for biochemical analysis with corresponding AFC substrates. Inhibitors gave similar results in the biochemistry and histochemistry. The inhibitor response and pH profile of the enzyme were the same as that found earlier with gingival homogenates and GCF and were again consistent with mast cell tryptase. The enzyme may have a role in the pathology of chronic periodontitis.

2-Naphthylamine↗
PubMedDate not supplied

Tryptase: a clinical indicator of mast cell-dependent events.

Mast cells and basophils are implicated as major effector cells in allergic disease. However, both mast cell and basophil involvement in clinical events have been difficult to assess heretofore because of localization of mast cells in tissues and the small numbers of basophils in the circulatory system. Tryptase has been found to be a discriminating marker for the participation of human mast cells in immediate allergic responses, and therefore provides precise assessment of mast cell activation. High tryptase levels in serum, plasma, and other biologic fluids are consistent with mast cell activation in systemic anaphylaxis and other immediate hypersensitivity allergic reactions. Although basophil activation has been implicated in late phase response to allergen challenge, sensitive specific indicators of basophil activation are still under investigation.

Anaphylaxis↗
PubMed1999

[Anaphylactic reaction to thiopental. A case documented by tryptase values and RAST].

During general anesthesia adverse reactions are not uncommon, and the hypothesis of an anaphylactic response cannot be excluded. In these situations, a differential diagnosis from other events which often present identical clinical manifestations is necessary. For this purpose measurement of serum tryptase, as a biochemical marker of the release of mast-cell granules, is considered a valuable and specific method, especially if it is carried out on several hematic samples, obtained in successive times, for pointing out the progressive reduction of the values. If an anapyhlactic pathogenesis is confirmed, the identification of the responsible drug is necessary for a safer approach of the patient in view of a further anesthesia. A severe and protracted reaction has been observed after a standard induction of anesthesia, in which measurement of serum tryptase has shown high values of this protease 2 hours after the reaction which a subsequent decrease in the samples repeated after 5, 8, 11 e 20 hours, suggesting an anaphylactic etiology of the reaction. The specific RAST for the substances employed has excluded a role for muscle relaxant, plasma expander and latex, while it was positive for tiopenthal, suggesting in this case a true anaphylactic reaction caused by the hypnotic drug.

Aged↗
PubMed1992

Determination of human mast cell tryptase by bioluminescence-enhanced two-site immunometric assay.

A highly sensitive bioluminescence-enhanced two-site immunometric assay for human mast cell tryptase was developed. The usable range of the standard curve was from 10 ng to 10 micrograms per litre. The intra-assay coefficient of variation of the test was between 8.0 and 12.3%, and the inter-assay coefficient of variation between 8.3 and 13.5%. Recovery of human mast cell tryptase in human serum was 100% (fraction of serum in the test sample: 0.30).

Buffers↗
PubMed1994

Interleukin-4 inhibits the expression of Kit and tryptase during stem cell factor-dependent development of human mast cells from fetal liver cells.

Although interleukin-4 (IL-4) in mice is known to augment the proliferation of mast cells and to modulate the expression of certain mast cell protease transcripts, its effect on human mast cells is less well understood. The current study examined the effects of recombinant human IL-4 (rhuIL-4) on stem cell factor (SCF)-dependent fetal liver-derived human mast cells in liquid culture. In no case did rhuIL-4 augment proliferation of mast cells. rhuIL-4 selectively inhibited certain aspects of the development of mast cells in cultures of fetal liver cells with rhuSCF. These include lower numbers and percentages of cells expressing tryptase and surface Kit, smaller cells, and lower contents of cells for tryptase, histamine, and Kit. Development of metachromasia was not attenuated. The downregulation of Kit, the surface receptor for SCF, is probably a critical factor, because cells lacking this molecule would not be able to respond to SCF. In contrast to mast cell progenitors, mast cells already developed in vitro from fetal liver cells are relatively resistant to rhuIL-4, but are still dependent for survival on the presence of rhuSCF.

Abortion, Therapeutic↗