Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The first crystal structure of an active autolysate form of porcine alpha-trypsin (APT), a two-chain molecule obtained from the limited autolysis of porcine beta-trypsin at position Lys145-Ser146, has been determined. APT crystallizes in space group P2(1)2(1)2(1) with one protein molecule in the asymmetric unit. The structure was solved by molecular replacement followed by refinement using X-PLOR to an R factor of 0.200 and an R(free) of 0.285 for 8.0-1.8 A data with r.m.s deviations from ideal values of 0.01 A and 1.7 degrees for bond lengths and bond angles, respectively. Comparison with inactive autolysate porcine epsilon-trypsin (EPT) and porcine beta-trypsin in complex with bittergourd trypsin inhibitor (MCT) revealed a small but systematic directional chain shift around the active-site residues from APT to EPT to MCT.
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PMID:The first structure at 1.8 A resolution of an active autolysate form of porcine alpha-trysoin. 1529 34

The aim of our study was evaluation of the results of clinical examination in patients with vasomotor and perennial allergic rhinitis and assessment of number of blood vessels, nerve fibres and mast cells on the basis of immunohistoenzymatic examination. There were 42 patients examined aged from 18 to 50 and divided into three groups: I--16 patients with vasomotor rhinitis and II--14 patients with perennial allergic rhinitis and III--12 patients (control) with nasal septum deviation. On the basis of the patient's history data, clinical otorhinolaryngologic examination and active anterior rhinomanometry the patients were qualified to bilateral inferior turbinectomy. The nasal mucosa removed during surgery underwent immunohistoenzymatic examination using the monoclonal antibody against the tryptase of mast cells (MCT company, DAKO), the endothelin of blood vessels (EC - DAKO) and the neurospecific enolase (NSE - DAKO). In examined groups of patients with vasomotor and perennial allergic rhinitis and control group similar escalation of clinical symptoms expressed by means of points index were stated. In immunohistoenzymatic studies the differences in mean number of blood vessels and nerve fibres between examined groups were not statistically significant, however statistically significant difference concerned higher number of mast cells patients with vasomotor rhinitis in comparison to perennial allergic rhinitis.
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PMID:[Clinical and immunohistoenzymatic investigations in patients with vasomotor and perennial allergic rhinitis]. 1585 83

The MC(TC) and MCT types of human mast cells initially were recognized on the basis of the protease compositions of their secretory granules, with tryptase, chymase, carboxypeptidase A3, and cathepsin G in the former and only tryptase in the latter. Antibodies against chymase and tryptase traditionally have been used to distinguish these mast cell types from one another. Antitryptase antibodies label all mast cells; antichymase labels only the MC(TC) type. To identify both types in a tissue section, a sequential double-labeling scheme was developed to first stain chymase-positive cells, thereby blocking their recognition by the antitryptase antibody, which will label only the chymase-negative mast cells. In general, these immunocytochemical techniques are more sensitive and specific than classical histochemical techniques for detecting mast cells.
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PMID:Analysis of MC(T) and MC(TC) mast cells in tissue. 1611 Jan 48

NKp46 (natural cytotoxic receptor 1/CD335) is expressed on natural killer cells and Th2-type innate lymphocytes. However, NKp46 expression in human mast cells has not yet been reported. Here, we explored the expression of, and possible role played by, NKp46 in such cells. NKp46 protein was expressed in human mast cells in urticaria pigmentosa principally of the tryptase-positive/chymase-negative type (MCT), but not in human non-neoplastic skin mast cells of the tryptase-positive/chymase-positive (MCTC) type. NKp46 expression was also evident in the human neoplastic mast cell line HMC1.2. NKp46 knockdown changed the phenotype of this cell line from MCT to MCTC and downregulated GrB production, but did not influence IL-22 production. An agonistic anti-NKp46 antibody upregulated production of GrB and IL-22, but did not change the MCT-like phenotype of HMC1.2 cells. NKp46 was thus involved in the production of serine proteases and IL-22 in human mast cells.
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PMID:NKp46 regulates the production of serine proteases and IL-22 in human mast cells in urticaria pigmentosa. 2594 96

The prognostic value of mast cells (MCs) in patients with liver metastases is a relatively new topic. The present study comparatively assessed tryptase-positive (MCT(+)) and CD117(+) MCs in liver metastases from various sites and correlated their expression with clinicopathological prognostic factors and survival. Our data pointed to differences in MCT and CD117 expression in liver metastases that seem to be related to the origin of the primary tumor. For colon cancer metastases, intra-tumor MCT(+) MCs were significantly correlated with tumor grade and nodal status, while peritumoral MCT(+) MCs and peritumoral CD117(+) MCs were significantly correlated with overall survival. No significant correlations between MCT(+) and CD117(+) MC number and clinicopathological parameters or survival were found for gastric cancer metastases. To the best of our knowledge, this is the first report regarding MC involvement in liver metastases from different malignant tumors correlated with clinicopathological parameters and overall survival. Different mast cell phenotype together with their specific correlation with tumor grade, nodal status and survival suggest their involvement in the metastatic process in a specific manner related to tumor origin. Mast cells from liver metastases remain a questionable issue regarding their origin, pathogenic role and their ability to be potential targets for adjuvant therapy.
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PMID:Tryptase-positive and CD117 Positive Mast Cells Correlate with Survival in Patients with Liver Metastasis. 2640 93

Mast cells are a resident inflammatory cell of the airways, involved in both the innate and adaptive immune response. The relationship between mast cells and inflammatory phenotypes and treatment response of asthma is not clear.Clinical characteristics of subjects with stable asthma (n=55), inflammatory cell counts and gene expression microarrays in induced sputum were analysed. Sputum mast cell subtypes were determined by molecular phenotyping based on expression of mast cell biomarkers (tryptase (TPSAB1), chymase (CMA1) and carboxypeptidase A3 (CPA3)). Effects of mast cell subtypes on steroid response were observed in a prospective cohort study (n=50).MCT(n=18) and MCT/CPA3(mRNA expression of TPSAB1 and CPA3; n=29) subtypes were identified, as well as a group without mast cell gene expression (n=8). The MCT/CPA3 subtype had elevated exhaled nitric oxide fraction, sputum eosinophils, bronchial sensitivity and reactivity, and poorer asthma control. This was accompanied by upregulation of 13 genes. Multivariable logistic regression identified CPA3(OR 1.21, p=0.004) rather than TPSAB1(OR 0.92, p=0.502) as a determinant of eosinophilic asthma. The MCT/CPA3 subtype had a better clinical response and reduced signature gene expression with corticosteroid treatment.Sputum mast cell subtypes of asthma can be defined by a molecular phenotyping approach. The MCT/CPA3 subtype demonstrated increased bronchial sensitivity and reactivity, and signature gene expression, which was associated with airway eosinophilia and greater corticosteroid responsiveness.
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PMID:Sputum mast cell subtypes relate to eosinophilia and corticosteroid response in asthma. 2703 11

Mast cells (MCs) play a pivotal role in the hypersensitivity reaction by regulating the innate and adaptive immune responses. Humans have two types of MCs. The first type, termed MCTC, is found in the skin and other connective tissues and expresses both tryptase and chymase, while the second, termed MCT, which only expresses tryptase, is found primarily in the mucosa. MCs induced from human adult-type CD34+ cells are reported to be of the MCT type, but the development of MCs during embryonic/fetal stages is largely unknown. Using an efficient coculture system, we identified that a CD34+c-kit+ cell population, which appeared prior to the emergence of CD34+CD45+ hematopoietic stem and progenitor cells (HSPCs), stimulated robust production of pure Tryptase+Chymase+ MCs (MCTCs). Single-cell analysis revealed dual development directions of CD34+c-kit+ progenitors, with one lineage developing into erythro-myeloid progenitors (EMP) and the other lineage developing into HSPC. Interestingly, MCTCs derived from early CD34+c-kit+ cells exhibited strong histamine release and immune response functions. Particularly, robust release of IL-17 suggested that these early developing tissue-type MCTCs could play a central role in tumor immunity. These findings could help elucidate the mechanisms controlling early development of MCTCs and have significant therapeutic implications.
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PMID:Early development and functional properties of tryptase/chymase double-positive mast cells from human pluripotent stem cells. 3312 75


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