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)

The knowledge about the differentiation of basophilic leukocytes is fragmentary. This report discusses a detailed phenotypic characterization of molecular markers for hematopoietic differentiation in a basophilic leukemia cell line, KU812. The expression of markers for lymphoid, erythroid, neutrophil, eosinophil, monocytic, megakaryocytic, mast cell and basophil differentiation was analyzed at the mRNA level by Northern blots in the KU812 cells, and for reference, in a panel of human cell lines representative of the different hematopoietic differentiation lineages. KU812 was found to express a number of mast cell and basophil-related proteins, i.e. mast cell tryptase, mast cell carboxypeptidase A, high-affinity immunoglobulin (IgE) receptor alpha and gamma chains and the core protein for heparin and chondroitin sulphate synthesis. We found no expression of a number of monocyte/-macrophage or neutrophil leukocyte markers except for lysozyme. From earlier studies, it has been shown that lysozyme is not expressed in murine mucosal mast cell lines. This finding, together with the expression of the mast cell carboxypeptidase in KU812 might distinguish the phenotype of this cell line from that typical of mucosal mast cell lines in rodents. We found a low level of expression of the eosinophil and basophil marker, major basic protein, which might indicate a relationship between basophils and eosinophils. No expression is, however, detected with the eosinophil-specific markers eosinophil cationic protein, eosinophil-derived neurotoxin or eosinophil peroxidase. We also report an extensive screening for inducers of basophilic differentiation of the KU812 cells. The most efficient protocol of induction included serum starvation which led to a dramatic increase in a number of markers specific for mast cells and basophils such as tryptase, carboxypeptidase A and the heparin core protein. Finally, diisopropylfluorophosphate analysis of total protein extracts from KU812 show four labeled protein bands with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that this cell line expresses at least three previously undescribed serine proteases of which one or more could be a potential basophil-specific marker(s).
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PMID:Phenotypic characterization of KU812, a cell line identified as an immature human basophilic leukocyte. 163 3

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

Clinical studies of vernal keratoconjunctivitis (VKC) patients show that total IgE serum levels are increased even in the absence of IgE antibodies to common allergens. Activated eosinophils are also a constant feature of VKC at both the circulation (cytofluorimetry) and tissue (tear cytology and conjunctival scrapings) levels. Moreover, allergen challenge induces a prolonged inflammatory reaction with a prevalent participation of eosinophils, lymphocytes and possibly basophils. Immunohistochemical studies of VKC biopsies show a multicellular inflammatory infiltrate with prevalence of activated eosinophils, mast cells and CD4 lymphocytes in both epithelium and subepithelium. Mediator studies indicate that eosinophil products (eosinophil peroxidase, eosinophinal cationic protein and eosinophil-derived neurotoxin/eosinophil protein X) are increased in both serum and tears, where tryptase and interleukin (IL)-5 are also detectable in higher amounts than in controls. On the basis of these findings, we postulate that VKC can represent a phenotypic model of up-regulation of the cytokine gene cluster on chromosome 5q which through its products (IL-3, IL-4, IL-5 and granulocyte/macrophage-colony-stimulating factor) regulates Th2 prevalence, IgE production as well as mast cell and eosinophil growth and function in VKC.
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PMID:Vernal keratoconjunctivitis: a model of 5q cytokine gene cluster disease. 761 25

The growing recognition of asthma as an immunologic disease mediated by inflammatory cells and mediators has changed the nature of therapy and monitoring of this disease. Modulation of inflammatory mediators such as leukotrienes, prostaglandins, and adenosine by specific immunoregulatory pharmacotherapy is now becoming well-recognized as essential for proper management of allergic diseases, including asthma. The newly-developed immunoassays for specific inflammatory cell activation markers, such as tryptase for mast cell activation, myeloperoxidase for neutrophil activation, and eosinophilic cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) for eosinophil activation, may significantly enhance the ability to both determine the cellular etiology of allergic inflammation and also to monitor the efficacy of antiinflammatory therapies in suppressing cell-specific immunologic events.
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PMID:Introduction: mediator assays and inflammatory events in asthma and allergic disease (Immunology Research Institute of New England Symposium). 792 8

This study presents the clinical and laboratory findings of a novel syndrome associated with eosinophilia. Two young women presented with marked eosinophilia, and large, non-tender compressible articular nodules arising from the tenosynovium of extensor tendons, dermatitis, episodic swelling of the hands and/or feet and pain in adjacent muscles and joints. Tissue specimens were examined by routine haematoxylin and eosin staining, immunofluorescent staining for eosinophil granule major basic protein (MBP) and rhodamine-avidin or tryptase staining for mast cells. Plasma levels of MBP and eosinophil-derived neurotoxin (EDN) were quantitated by immunoassay. The first patient presented in 1967 at the age of 20 and had, in addition to nodules and eosinophilia, dermographism, recurrent episcleritis and axillary urticaria. Biopsy of a nodule showed tenosynovitis with necrotizing granulomas, non-specific vasculitis, eosinophils and eosinophil degranulation as shown by extracellular deposition of eosinophil granule MBP. Her symptoms responded to low-dose, alternate-day prednisone and have remained quiescent over the past 15 yr. The second patient presented in 1990 at the age of 28 with generalized pruritic dermatitis for 15 yr, eosinophilia for 2 yr, subcutaneous nodules and non-limiting pain in several joints. Biopsy of a nodule showed chronic mild tenosynovitis, numerous eosinophils and extracellular deposition of MBP. She remains untreated. Serum IgE values and plasma levels of MBP and EDN were elevated in both patients; mast cells were numerous in their synovial tissue. Based on their clinical courses, these patients reveal the existence of a distinctive, relatively benign eosinophilic disorder with good long-term prognosis.
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PMID:Nodules, eosinophilia, rheumatism, dermatitis and swelling (NERDS): a novel eosinophilic disorder. 822 Dec 54

Methods to examine sputum for indices of airway inflammation are evolving. We have examined the repeatability and the validity of an improved method to measure sputum cells and fluid-phase eosinophil cationic protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), albumin, fibrinogen, tryptase, and interleukin-5 (IL-5). Sputum was induced with hypertonic saline twice within 6 d in 10 healthy subjects, 19 stable asthmatics, and 10 smokers with nonobstructive bronchitis. The method included the processing of freshly expectorated sputum separated from saliva, treatment with a fixed proportion of dithiothreitol 0.1% followed by Dulbecco's phosphate-buffered saline, making cytospins, and collecting the supernatant. The reproducibility of measurements, calculated by the intraclass correlation coefficient, was high for all indices measured with the exception of total cell counts and proportion of lymphocytes. Asthmatics, in comparison with healthy subjects and smokers with bronchitis, had a higher proportion of sputum eosinophils (median percent 5.2 versus 0.5 and 0.3), metachromatic cells (0.3 versus 0.07 and 0.08), ECP (1,040 micrograms/L versus 288 and 352), MBP (1,176 micrograms/L versus 304 and 160), and EDN (1,512 micrograms/L versus 448 and 272). Asthmatics differed from healthy subjects, but not from smokers with bronchitis, in the proportion of neutrophils (46.9% versus 24.1%), albumin (704 versus 288 micrograms/mL), and fibrinogen (2,080 versus 440 ng/mL). Smokers with bronchitis showed a trend for a higher neutrophil count and levels of albumin and fibrinogen than healthy subjects. The proportion of sputum eosinophils correlated positively with ECP, MBP, EDN, albumin and fibrinogen levels, and metachromatic cell counts correlated with tryptase. In asthmatics, IL-5 correlated with eosinophil counts. There was a significant negative correlation between sputum indices and expiratory flows and methacholine PC20. Thus, the methods of measuring cell and fluid phase markers in induced sputum used in this study are reproducible and valid. They can therefore be used to reliably measure these indices of airway inflammation.
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PMID:Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. 2597 85

Eosinophilia in humans is often associated with heart disease and cardiac localization of eosinophil granule proteins, and several results suggest that granule proteins mediate endomyocardial damage. Here we investigated the in vitro effects of the four principal eosinophil granule proteins (eosinophil cationic protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin, and eosinophil peroxidase (EPO)) on the activation of effector cells of inflammation (mast cells) isolated from human heart tissue (HHMC). ECP and, to a lesser extent, MBP (0.3-3 microM), but not eosinophil-derived neurotoxin and eosinophil peroxidase stimulated the release of preformed (histamine and tryptase) and the de novo synthesis of vasoactive and proinflammatory mediators (PGD2) from HHMC. Activation of HHMC by ECP and MBP was Ca2+- and temperature-dependent and was abolished by preincubation (15 min, 37 degrees C) with 2-deoxy-D-glucose (10 mM) and antimycin A (1 microM). There was a significant correlation between the maximal percentage of histamine release induced by ECP and anti-IgE from HHMC (rs = 0.73; p < 0.005), by MBP and anti-IgE (rs = 0.79; p < 0.001), and by ECP and MBP (rs = 0.65; p < 0.005). A positive correlation was also found between histamine and tryptase secretion (rs = 0.71; p < 0.001) and between histamine and PGD2 release induced by ECP from HHMC (rs = 0.85; p < 0.001). This is the first demonstration that some eosinophil cationic proteins, namely ECP and MBP, found at the site of heart damage in patients with eosinophilia, act as complete secretagogues on HHMC. This observation indicates another mechanism by which infiltrating eosinophils and their metabolic products cause inflammatory reactions and thus endomyocardial lesions in patients with eosinophilia.
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PMID:Eosinophil granule proteins activate human heart mast cells. 875 29

Eosinophilia in humans is associated with eosinophil infiltration and cardiac localization of eosinophil granule proteins. Eosinophil cationic proteins are responsible for cardiac disease in some patients with eosinophilia. We have investigated the in vitro effect of four eosinophil granule proteins: eosinophil cationic protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin (EDN) and eosinophil peroxidase (EPO), on mast cells isolated from human cardiac tissue (HHMC). ECP and, to a lesser extent MBP (0.3-3 microM), but not EDN and EPO, stimulated the release of histamine and tryptase from HHMC. This release reaction induced by ECP and MBP was Ca(2+)- and temperature-dependent and was abolished by preincubation with anti-ECP and anti-MBP, respectively. The activation of HHMC by ECP and MBP was abolished by preincubation with 2-deoxy-D-glucose and antimycin A. These data demonstrate that some eosinophil cationic proteins, ECP and MBP, are selective activators of HHMC, thus contributing to the cardiac lesions in patients with eosinophilia.
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PMID:Eosinophil granule proteins are selective activators of human heart mast cells. 913 May 22

Polymorphic eruption of pregnancy (PEP) and herpes gestationis (HG) are pregnancy-related dermatoses of unknown aetiology with eosinophil infiltration which, at early stages, may show similar clinical and histopathological features. To determine the relative contributions of eosinophils, neutrophils and mast cells to the pathogenesis of PEP and HG through deposition of granule proteins, we studied tissue and serum from 15 patients with PEP and 10 with HG. Using indirect immunofluorescence with antibodies to human eosinophil granule major basic protein (MBP), eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), neutrophil elastase and mast cell tryptase, we determined and compared cellular and extracellular staining patterns in lesional skin biopsy specimens and, using immunoassay, measured MBP, EDN, and ECP in patients' sera. Eosinophil infiltration and extracellular protein deposition of all three eosinophil granule proteins were present in both PEP and HG indicating a pathogenic role for eosinophils in both diseases. Staining for eosinophil granule proteins was especially prominent in urticarial lesions and around blisters in HG. EDN and ECP serum levels in PEP and ECP serum levels in HG were significantly increased compared with those in normal pregnant and normal nonpregnant serum. Neutrophils were more prominent in HG specimens than in PEP specimens; extracellular neutrophil elastase was minimally present and similar in both diseases. Mast cell numbers and extracellular tryptase deposition did not differ between the two diseases and did not differ from mast cell counts in skin of normal pregnant women. This study shows that eosinophil granule proteins are deposited extracellularly in tissue and are increased in serum in both PEP and HG. Moreover, eosinophil involvement in the two diseases is more consistent than neutrophil and mast cell involvement. Comparatively, tissue eosinophil infiltration and extracellular protein deposition is more extensive in HG than in PEP, suggesting that eosinophil involvement is greater in the pathogenesis of HG than PEP and similar to that found in bullous pemphigoid.
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PMID:Polymorphic eruption of pregnancy and herpes gestationis: comparison of granulated cell proteins in tissue and serum. 1035 84

To investigate the role of mast cells in treatment-associated adverse reactions in patients with onchocerciasis, changes in plasma tryptase levels and skin mast cell counts were examined in 2 groups of Onchocerca volvulus-infected subjects after ivermectin treatment. After treatment, an increase in tryptase levels was observed concurrent with the onset of blood eosinopenia and preceding the appearance of plasma eosinophil-derived neurotoxin (EDN) and interleukin-5. Tryptase levels were correlated with development of peripheral eosinopenia and markers of eosinophil activation and degranulation. Dermal mast cell numbers increased transiently at 24 h after treatment, preceding the onset of dermal eosinophil infiltration and the development of clinically apparent inflammation. Local reactions were strongly correlated with levels of plasma tryptase and EDN, and the severity of systemic reactions was correlated with levels of tryptase, EDN, and interleukin-5. The data indicate that mast cells play a role in initiation of tissue inflammatory reactions after ivermectin treatment of onchocerciasis.
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PMID:Association of transient dermal mastocytosis and elevated plasma tryptase levels with development of adverse reactions after treatment of onchocerciasis with ivermectin. 1240


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