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)

We found a novel trypsin-like enzyme (tryptase) in sputum from patients with chronic airway diseases, and named this enzyme human airway tryptase (HAT). To clarify its physiological significance in the airway, we compared biochemical properties of purified HAT with those of purified lung mast cell tryptase (MCT). Studies with model peptide substrates showed that both the HAT and MCT preferentially cleaved the COOH-terminal side of arginine residues of certain peptides, but substrate specificities to nine synthetic model substrates of HAT differed from those of MCT. Effects of protease inhibitors on the two enzymes were examined at a concentration of 10 microM. Both the HAT and MCT were strongly inhibited by the trypsin inhibitors leupeptin, antipain, and aprotinin. An alpha-1-protease inhibitor inhibited HAT by 50%, but it did not inhibit MCT. In contrast, a secretory leukocyte protease inhibitor strongly inhibited MCT, but not HAT. Mucoid sputum from patients with chronic bronchitis contained much more HAT than MCT. These differences in biochemical properties between HAT and MCT indicate that they play different physiological roles in the airways.
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PMID:[Comparison of biochemical properties of human airway tryptase isolated from mucoid sputum with those of lung mast cell tryptase]. 874 34

Mast cells and blood basophils are distinct hemopoietic cells. They can be distinguished from each other and from all other lymphohemopoietic cells using antibodies against surface receptors or stored cytoplasmic molecules. In patients with myelodysplastic syndromes (MDS) or myeloproliferative syndromes (MPS), an elevation of metachromatically granulated cells (MCS) is frequently seen. These cells can be classified as basophils or mast cells using monoclonal antibodies (mAbs) against leukocyte antigens, including mast cell tryptase, c-kit (= mast cell growth factor [MGF] receptor), interleukin-3 receptor alpha chain (IL-3R alpha = CD123), and CD11b (C3biR). In a stable phase of MDS or MPS, the circulating MCS usually are basophils (histamine+, tryptase-, c-kit-, IL-3R alpha +, CD11b+). In an accelerated or terminal phase of disease, however, mast cell lineage involvement and circulating mast cell precursors (histamine+, tryptase+, c-kit+, IL-3R alpha-, CD11b-) are found in a subset of patients. The use of mAbs against mast cell antigens and granulocyte antigens is diagnostic in these patients.
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PMID:Mast cell-lineage versus basophil lineage involvement in myeloproliferative and myelodysplastic syndromes: diagnostic role of cell-immunophenotyping. 881 68

Exercised mdx mice were used to evaluate the efficacy of two pharmacologic entities, cromolyn and compound 48/80. Beginning at 2 weeks of age, mdx mice were treated with either cromolyn (50 mg/kg/day), prednisone (2mg/kg/day), compound 48/80 (1mg/kg/day), or diluent vehicle. At 4 weeks of age, treated mice were subjected to twice weekly, forced treadmill running which has previously been shown to cause expressed weakness in mdx mice (Hudecki, Pollina et al., 1993). Strength was evaluated weekly through 6 weeks of age using a previously described "pull-test" procedure (Hudecki, Pollina et al., 1993). Serum creatine kinase (CK) and mast cell tryptase activities were evaluated from 6 week blood samples. There was a significant increase in strength in mdx mice treated with cromolyn (p < or = 0.05), while no significant increase in strength was found in mice treated with compound 48/80, or prednisone compared to vehicle controls. While no significant change in tryptase activity was found between treatments, CK activity was significantly increased in the cromolyn group compared to vehicle controls. However, when tryptase and CK were expressed as a combined factor (Tryp x CK), the cromolyn treated group was significantly different from all other groups. The results of this study suggest a possible use for cromolyn-like compounds in the treatment of Duchenne muscular dystrophy.
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PMID:Cromolyn increases strength in exercised mdx mice. 882 68

Inflammatory and developmental cysts of the jaws are relatively common bone destructive lesions in the human maxillofacial skeleton but their pathogenesis is still poorly understood. In this study the role of mast cells (MC), and mast cell tryptase in particular, was evaluated in the pathophysiology of bone resorption and jaw cyst formation in different types of cysts. The distribution of MC and the amount of tryptase in histological tissue sections were determined by immunohistochemistry using monoclonal antihuman tryptase antibodies and the results were quantitated by using an image analyzing system. The amount of tryptase was further studied by Western-blotting and measurement of trypsin-like activity from the neutral salt extracts obtained from different types of jaw cysts. In contrast to control tissue, high trypsin-like activities and abundant immunoreactive tryptase were observed in the extracts of all types of cysts studied (radicular, dentigerous and keratocyst). In tissue sections the highest amount of tryptase-positive staining was observed in radicular cysts (mean 6.2% of reference area) and the lowest amount in keratocysts (mean 2.1% of reference area, P < 0.01). MC were found to be located in inflammatory cell-rich tissue areas and just beneath the cyst epithelium. Importantly, MC located at the border of bone were observed to be degranulated, indicating high activity of MC and release of tryptase at the regions of early bone destruction. Based on previous findings addressing the role of mast cell tryptase in proteolytic cascades, and the known association of MC with osteoporosis, we suggest that mast cells and mast cell tryptase may contribute significantly to jaw cyst tissue remodelling during growth of a cyst, and to the destruction of the surrounding bone, resulting in jaw cyst expansion.
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PMID:Mast cell-derived tryptase in odontogenic cysts. 889 52

Rat mast cell tryptase was purified to homogeneity from rat tongue by a series of standard chromatographic procedures. Since the enzyme gave band corresponding to molecular mass of 32-35 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis and exhibited a molecular mass of 135 kDa on gel filtration, it was presumed to be a noncovalently associated tetramer. The N-terminal amino acid sequence of 50 residues of the enzyme showed the highest degree of homology with the same region in mouse mast cell protease 7 (92%), and less homology to those of tryptases from man and dog, and peritoneal cells of rats and Mongolian gerbils. The inhibitor specificity of rat tongue tryptase was similar to that of rat peritoneal mast cell tryptase free from trypstatin: it was inhibited by alpha 1-antitrypsin, Kunitz-type soybean trypsin inhibitor and Bowman-Birk soybean trypsin inhibitor, but these inhibitors do not inhibit the tryptases from rat skin, human lung, and dog mast cells. Judging from these results, together with other enzymatic properties, the enzyme may be a novel isoform of tryptase in rat tongue. Analysis by differential staining with peroxidase-labeled lectins of the enzyme suggested that it has tri- and/or tetraantennary complex-type oligosaccharides containing a relatively high amount of sialic acid. The immunohistochemical distribution of this enzyme indicated that the reactive antigen was specific in connective tissue but not in mucosal mast cells.
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PMID:Purification and characterization of a novel isoform of mast cell tryptase from rat tongue. 894 53

To study the elements of neurogenic inflammation in psoriatic skin, morphological contacts were examined between mast cells and sensory nerves containing the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP) or vasoactive intestinal polypeptide (VIP). Because mast cells in psoriatic lesions appear in great numbers at the basement membrane (BM) zone, neuropeptide-mast cell contacts with the BM were also counted. A double stain for active mast cell tryptase and the neuropeptides was applied and the contacts were quantitated morphometrically. Sensory nerve-mast cell contacts were also studied three-dimensionally with a confocal laser scanning microscope. Increases in the contact values of SP and CGRP with mast cells, as well as with the BM, were obtained in developing (1-3 weeks) lesions when compared with their non-lesional controls. This increase reached statistical significance in mature lesions. In contrast, the corresponding contact values for VIP were decreased. By confocal microscopy, a close association between mast cells and sensory nerves was observed in the lesional dermis. Since tryptase is known to degrade CGRP but not SP, neurogenic stimuli, mainly via SP, can result in degranulation of mast cells, which release substances to enhance inflammation. At the BM zone in psoriatic lesions, the numerous mast cells loaded with tryptase can promote degradation of BM components and allow entry of various mediators to interact with keratinocytes.
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PMID:Quantitative histochemical analysis of mast cells and sensory nerves in psoriatic skin. 897 81

We have applied the technique of sputum induction by hypertonic saline in asthmatics and nonatopic control subjects to study an array of indices of airway inflammation believed to be relevant to asthma pathogenesis. Compatible with a central role for eosinophils and mast cells in asthma, sputum of asthmatic subjects contained increased numbers of eosinophils and levels of eosinophil cationic protein (ECP) and mast cell tryptase. Eosinophil numbers, and ECP and histamine levels correlated with the degree of methacholine airways responsiveness, and ECP, tryptase, and histamine correlated with raised concentrations of albumin. Using the micro-Boyden chamber technique eosinophil chemotactic activity was identified only in the sputum from asthmatics. The correlation between the raised levels of total IgA, IL-8/IgA complexes, and tryptase and the degree of sputum eosinophilia and ECP levels, suggests possible mechanisms for eosinophil chemotaxis and activation in asthma. Row cytometric analysis of sputum lymphocytes showed an increase in CD4+ T cells and T cells expressing intercellular adhesion molecule-1 (ICAM-1) in asthma which, together with the finding of raised levels of soluble ICAM-1 in the sputum, indicates upregulation of this adhesion molecule. Finally, the proportion of CD16+ natural killer (NK) cells was reduced in the sputum of asthmatics. These observations highlight the importance of the airway inflammation in causing asthma and further confirm the usefulness of sputum induction as a tool in asthma research.
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PMID:Cell infiltration, ICAM-1 expression, and eosinophil chemotactic activity in asthmatic sputum. 903 80

The mast cell plays a pivotal role in the early asthmatic response via release of mediators, which directly influence airway smooth muscle tone. Canine mast cell tryptase has been reported to potentiate the contractile response of canine isolated airways to histamine. The aim of this study was to investigate whether human mast cell tryptase potentiated contractile responses in human isolated bronchi. The effect of tryptase differed according to the sensitization status of the bronchi. In lung tissue from sensitized patients (those whose bronchial tissue contracted in response to the application of any of four common antigens) 90 ng.mL-1 of human purified lung tryptase markedly potentiated the contractile response to histamine. The maximal response as a percentage of maximal contraction to acetylcholine was 80 +/- 8% in control tissues and 119 +/- 6% in tryptase treated tissues (n = 4; p < 0.05). Tryptase, at a dose of 200 ng.mL-1, also potentiated responses but to a lesser degree, 100 +/- 5% (n = 4; p < 0.05). In nonsensitized bronchi, neither 90 nor 200 ng.mL-1 tryptase had any significant effect on histamine responses. The increased response in the presence of tryptase in sensitized tissue was inhibited by the calcium voltage-dependent channel antagonist, verapamil (10(-6) M). We have shown, for the first time, that human mast cell tryptase potentiates contraction in sensitized bronchi via a calcium-related mechanism. These findings provide a link between a mast cell derived product and in vitro human airway hyperresponsiveness.
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PMID:Mast cell tryptase potentiates histamine-induced contraction in human sensitized bronchus. 903 89

The ability of human mast cell chymase and tryptase to process procollagen was examined. Purified human intestinal smooth muscle cell procollagen was incubated with human mast cell tryptase or human mast cell chymase. Purified chymase, but not tryptase, exhibited procollagen proteinase activity in the presence of EDTA. Addition of purified porcine heparin over a range of 0.1-100 microg/ml did not affect either the rate or the products of procollagen chymase cleavage. The cleavage site of chymase on the pro-alpha1(I) collagen carboxyl terminus was found to be in the propeptide region at Leu-1248-Ser-1249. Cleavage at this site suggested that the collagen products would form fibrils and confirmed the production of a unique carboxyl-terminal propeptide. Turbidometric fibril formation assay demonstrated de novo formation of chymase-generated collagen fibrils with characteristic lag, growth, and plateau phases. When observed by dark field microscopy, these fibrils were similar to fibrils formed by the action of procollagen proteinases. Thus, mast cell chymase, but not tryptase, exhibits procollagen peptidase-like activity as evidenced by its ability to process procollagen to fibril-forming collagen with concurrent formation of a unique carboxyl-terminal propeptide. These data demonstrate that mast cell chymase has a potential role in the regulation of collagen biosynthesis and in the pathogenesis of fibrosis.
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PMID:Cleavage of type I procollagen by human mast cell chymase initiates collagen fibril formation and generates a unique carboxyl-terminal propeptide. 905 7

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.
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PMID:GM-CSF downregulates expression of tryptase, Fc epsilon RI and histamine in HMC-1 mast cells. 913 May 50


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