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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both human and mouse c-kit ligand induced differentiation of human mast cells in a long-term culture of the mononuclear cells of umbilical cord blood. Growth factor activity for human mast cells present in conditioned medium of BALB/3T3 fibroblasts was due to mouse c-kit ligand. Recombinant c-kit ligand induced differentiation and proliferation of mast cell progenitors in early stages of culture. However, apparent selective growth of mast cells by c-kit ligand in cord blood cell cultures is mainly due to the effect of the cytokine to selectively maintain survival of immature mast cells. Electron microscopic analysis indicated that human mast cells developed by c-kit ligand were similar to human mast cells in the lung and gut mucosa, while those developed in coculture of cord blood cells with Swiss albino/3T3 fibroblasts were similar to skin mast cells. This conclusion was supported by the fact that the majority of mast cells developed by c-kit ligand contained only tryptase in their granules, whereas those developed in the cocultures contained both tryptase and chymase. It was also found that mast cells developed by c-kit ligand were immature even after culture for 14 weeks. Nevertheless, these cells express Fc epsilon RI, and could be sensitized with human IgE for anti-IgE-induced release of histamine, prostaglandin D2, and leukotriene C4.
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PMID:Development of human mast cells from umbilical cord blood cells by recombinant human and murine c-kit ligand. 767 63

Media conditioned by compound 48/80-stimulated rat mast cells generated immunoreactive histamine-releasing peptide (HRP) when incubated at physiological pH with bovine serum albumin and the carboxypeptidase inhibitor, O-phenanthroline. The generation of immunoreactive HRP (IR-HRP) was time (after 3 h the concentration of IR-HRP was 20 nM), temperature, and pH dependent and was prevented by omitting albumin, by using media conditioned by nonstimulated mast cells, or by pretreatment of mast cells with disodium cromoglycate, an inhibitor of mast cell secretion. The amount of IR-HRP generated increased linearly with the number of mast cells stimulated and varied directly with the concentration of conditioned media. After removal of the media from stimulated mast cells, the remaining cell pellet retained its ability to generate IR-HRP for up to 8 h. Stimulation of mast cells by either neurotensin or substance P, or of sensitized cells by anti-IgE serum, also produced conditioned media that generated IR-HRP. The amount of IR-HRP formed by various conditioned media or by stimulated cell pellets was dependent upon the concentration of O-phenanthroline used. Including the chymase inhibitor, chymostatin, prevented the formation of IR-HRP in a dose-dependent manner. HPLC analysis showed four peaks of IR-HRP. The major one coeluted with synthetic HRP. These results indicate that the peptide, HRP, can be generated by stimulated mast cells incubated in the presence of albumin. They suggest that a chymase-like enzyme secreted by the mast cell is able to cleave albumin to yield HRP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulated rat mast cells generate histamine-releasing peptide from albumin. 768 97

We studied the effect of mast cell chymase on the interaction between osteoblasts and extracellular matrix. Chymase was purified from mast cell lysate by anion exchange chromatography. Osteoblasts were isolated from rat calvarias by collagenase digestion. Incubation of osteoblasts with mast cell lysate (40-170 micrograms/ml) or purified chymase (8-32 micrograms/ml) resulted in changes in cell-matrix interaction and cell morphology. Osteoblasts treated with chymase also showed a gradual detachment from the artificial substrata and from the biomatrix (collagen-digested rib fragment). A similar effect of mast cell chymase on the osteoblasts was found in vitro on endosteum of an intact parietal bone. Neutral protease inhibitors abolished the effect of both crude and purified enzyme preparations on the cell-matrix interaction. Mast cell chymase had no effect on osteoblast viability. The effect of enzyme on osteoblast proliferation was studied with lower concentrations of enzyme (0.2 micrograms/ml) in order to avoid cell detachment; there was no effect on either the metaphase index or on the number of cells after 5 days of incubation with chymase. Osteoblast attachment and cell spreading on different matrix proteins (fibronectin, vitronectin, extract of noncollagenous matrix proteins from rat bone) were significantly altered by their pretreatment with chymase. Matrix fibronectin of osteoblasts in culture as well as soluble vitronectin and fibronectin were digested by rat mast cell chymase. Our data suggest that mast cells through action of neutral protease chymase may alter molecules in extracellular matrix that are important in osteoblast adhesion, cell spreading, maintenance of cell morphology, and, most likely, cell function.
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PMID:Interaction of osteoblasts with extracellular matrix: effect of mast cell chymase. 768 44

Mast cell neutral proteases are the most precise markers of heterogeneity among human mast cells. Two types of human mast cells have been recognized. MCTC cells contain tryptase together with chymase, cathepsin-G like protease, and mast cell carboxypeptidase; MCT cells contain tryptase, but lack the other neutral proteases present in MCTC cells. All mast cells develop from hemopoietic stem cells. In vitro procedures for studying mast cell growth have been developed, using the major human mast cell growth factor, stem cell factor (SCF, also called Kit-ligand). Cultures of hemopoietic progenitor cells in the presence of SCF alone result in selective differentiation to mast cells. The same progenitor cells can be induced to differentiate into other lineages when SCF is used with various lineage-specific colony-stimulating factors such as erythropoietin for erythrocytes. Mast cell development from hematopoietic progenitors may represent a "default pathway," occurring optimally in a permissive microenvironment such as skin, bowel, and lung. The presence or absence of certain cytokines in blood and bone marrow may create a non-permissive environment, thus the absence of granulated mast cells in such locations.
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PMID:Human mast cell heterogeneity. 772 Oct 78

The role of mast cells in provoking immediate-type hypersensitivity reactions is well established, but their involvement in chronic inflammation and immune reactions is not so clear. Mast cells synthesize and secrete large amounts of active proteinases, including tryptase, chymase, carboxypeptidase and cathepsin G, which can rapidly process numerous biologically active peptides and proteins or their precursors. Furthermore, mast cells are able to produce a variety of cytokines such as interleukin-4 (IL-4), IL-5, IL-6, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) which are known to be intensively involved in modulating and directing inflammatory responses in the skin. In this review, the role of mast cell proteinases and cytokines in skin inflammation is discussed.
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PMID:Mast cell proteinases and cytokines in skin inflammation. 772 38

Allergic eye disease has a variety of clinical manifestations including seasonal atopic conjunctivitis (SAC), perennial atopic conjunctivitis (PAC), atopic keratoconjunctivitis (AKC), and atopic blepharoconjunctivitis (ABC). We have investigated the number, distribution and protease expression of mast cells in normal and diseased conjunctiva with the use of immunohistochemistry in water-miscible resin sections. The median mast cell densities in normal subjects were 17 mm-2 in the bulbar substantia propria and 9 mm-2 in tarsal substantia propria. Mast cells were absent from the normal conjunctival epithelium at both sites. Mast cell densities were increased in the bulbar substantia propria in SAC, AKC and ABC. Tarsal substantia propria showed a significant increase in mast cells in ABC and AKC disease states. Mast cells express a range of proteases which varies according to their anatomic site. Mast cells in connective tissue are described to contain tryptase, chymase, cathepsin-G and carboxypeptidase-A, whereas mucosal mast cells contain only tryptase. In the diseased conjunctiva there was a marked reduction in proteases other than tryptase in the intraepithelial mast cells. There were also significant reductions in protease expression other than tryptase in the bulbar substantia propria in AKC and ABC. There appear to be specific alterations in the distribution of mast cells in the sub-categories of allergic eye disease. The distinction between mucosal and connective tissue mast cell phenotypes is not clear-cut and may depend on the functional state of the mast cells in relation to the microenvironment.
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PMID:Mast cell distribution and neutral protease expression in acute and chronic allergic conjunctivitis. 772 24

Competitive reverse transcription-PCR assays developed for human tryptase, chymase, Fc epsilon RI alpha, and Fc epsilon RI gamma mRNA molecules were applied to the HMC-1 leukemic mast cell line, the KU812 leukemic basophil cell line, mast cells dispersed from lung and skin, and peripheral blood basophils. Relative amounts of alpha-tryptase and beta-tryptase mRNA were determined by analysis of BseAI digests of PCR products. Tryptase expression was highest in tissue-derived mast cells, lowest in basophils and KU812 cells, and intermediate in HMC-1 cells. beta-Tryptase mRNA predominated in HMC-1 and KU812 cells; mixtures of alpha- and beta-tryptase were found in tissue mast cells; and alpha-tryptase predominated in basophils. Chymase mRNA was more abundant in skin-derived (nearly all of the MCTC type) than lung-derived (variable amounts of MCTC and MCT cells) mast cells. Small amounts of chymase mRNA were detected in HMC-1 cells; none was found in basophils, in KU812 cells, or in the one preparation of 100% MCT cells derived from lung. Comparable amounts of Fc epsilon RI alpha and Fc epsilon RI gamma mRNA molecules were measured in basophils and tissue-derived mast cells, lesser amounts were detected in KU812 cells, and almost none was detected in HMC-1 cells. Thus, steady state levels of the granule and membrane resident molecules examined in our study are transcriptionally regulated in mast cells and basophils.
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PMID:Quantitation of tryptase, chymase, Fc epsilon RI alpha, and Fc epsilon RI gamma mRNAs in human mast cells and basophils by competitive reverse transcription-polymerase chain reaction. 773 Jun 49

The distribution and density of metachromatic cells (MCC) and mast cells containing chymase plus tryptase (MCTC) or tryptase alone (MCT) were studied in the nasal mucosa by dye-binding methods and immunohistochemical analysis. Biopsies were obtained from 17 subjects with birch pollen allergy before and during the peak season and from nine healthy controls. Six patients were treated with an intranasal glucocorticosteroid before and during the season in an open study. Hay fever patients, even when asymptomatic, showed signs of mast cell system activation, exhibiting an increased number of mast cells in the nasal epithelium. Basophils, lacking immunohistochemically detectable tryptase, were not a major component of the mast cell response. MCT, most conspicuous in the epithelium, were found to be the most frequent mast-cell type in the nasal mucosa of allergic, but not of normal, subjects. Only 33% of the epithelial, but 90% of the stromal, immunopositive cells in the atopic mucosa before as well as during the season were MCC. Intraepithelial MCT thus displayed a low capacity to stain metachromatically, indicating a relative deficiency of the glycosaminoglycan (heparin) component of the granules. Intraepithelial mast cells also appeared to be markedly sensitive to steroid treatment and aldehyde fixation. The findings suggest that the lack of chymase, the characteristic feature of MCT, may reflect a functional activation of the mast cells, rather than a stable phenotypic differentiation related to anatomic site.
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PMID:Proteinase content of mast cells of nasal mucosa; effects of natural allergen exposure and of local corticosteroid treatment. 774 Nov 84

Human prochymase is packaged with heparin in mast cell granules and appears to be activated by dipeptidylpeptidase I. We show that a high affinity interaction between heparin and prochymase allows the 2-residue propeptide to be cleaved by dipeptidylpeptidase I. A conserved Glu in the propeptide is necessary for this heparin effect. Following propeptide cleavage, capture of the newly generated NH2 terminus by an "activation groove" on the enzyme activates the enzyme and concurrently prevents a progressive degradation of the NH2 terminus by dipeptidylpeptidase I. Surrogate peptide studies show that the activation groove is unoccupied in prochymase and is specific for the chymase NH2 terminus. These observations indicate that heparin is an important cofactor in the prochymase activation process and explain how dipeptidylpeptidase I, a nonspecific processing enzyme, can effect a specific cleavage of the zymogen propeptide.
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PMID:Human prochymase activation. A novel role for heparin in zymogen processing. 783 53

We have demonstrated for the first time that a conditioned medium from a human cell strain can induce morphologically mature mast cells that express Fc epsilon RI and three mast cell-specific proteases from normal bone marrow progenitor cells. In contrast, recombinant human Kit ligand induced the differentiation of mast cells that were tryptase-positive but negative for chymase, carboxypeptidase, and Fc epsilon RI. This data indicates that factors other than Kit ligand are critical for inducing the differentiation and maturation of mast cells in the human. The HBM-M cell was originally derived from a patient with mastocytosis. As mastocytosis is thought to represent a reactive hyperplasia rather than a mast cell malignancy, the factor secreted by the HBM-M cell strain could well be responsible for the mast cell hyperplasia seen in some patients with mastocytosis.
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PMID:Conditioned media from a cell strain derived from a patient with mastocytosis induces preferential development of cells that possess high affinity IgE receptors and the granule protease phenotype of mature cutaneous mast cells. 783 59


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