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

A long-term co-culture of mononuclear cells of human umbilical cord blood with mouse embryo-derived 3T3 fibroblasts resulted in the development of human mast cells. These mast cells are morphologically and functionally mature cells, containing 1.4-2.8 micrograms histamine per 10(6) cells and bear approximately 10(5) Fc epsilon RI per cell. The mast cells sensitized with human IgE released histamine upon challenge with anti-IgE. Electron-microscopic analysis of the cells showed that these cells were mature human mast cells, and clearly different from basophilic granulocytes. Most of the mast cells contained some granules with regular crystalline arrays and both tryptase and chymase, resembling human skin mast cells. When mononuclear cells of cord blood were seeded in a millicell insert which was placed on 3T3 fibroblasts monolayer, the number of mast cells developed in the millicell inserts was comparable to those developed in the co-culture of the same cord blood cells with 3T3 fibroblasts. Recent observations that mast cells developed in the presence of concentrated culture supernatants of 3T3 fibroblasts without fibroblasts feeder layers, confirmed that soluble factors released from 3T3 fibroblasts are essential and sufficient for the differentiation of human mast cell progenitors in vitro. Analysis of functional characteristics of cultured mast cells revealed that they respond to anti-IgE, Ca2+ ionophore A23187 and substance P for histamine release, but failed to respond to compound 48/80 and FMLP. Upon anti-IgE challenge, sensitized mast cells generated approximately 80 ng PGD2 per 10(6) cells, and approximately 50 ng of LTC4 per 10(6) cells but no detectable generation of LTB4.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro development and functions of human mast cells. 193 64

A novel plasminogen-binding protein has been isolated from human plasma utilizing plasminogen-Sepharose affinity chromatography. This protein copurified with alpha 2 antiplasmin when the plasminogen affinity column was eluted with high concentrations of epsilon-aminocaproic acid (greater than 20 mM). Analysis by sodium dodecyl sulfate suggests this protein has an apparent Mr of 60,000. The amino-terminal amino acid sequence showed no similarity to other protein sequences. Based on the amino-terminal amino acid sequence, oligonucleotide probes were designed for polymerase chain reaction primers, and an approximately 1,800 base pair cDNA was isolated that encodes this Mr 60,000 protein. The deduced amino acid sequence reveals a primary translation product of 423 amino acids that is very similar to carboxypeptidase A and B and consists of a 22-amino acid signal peptide, a 92-amino acid activation peptide, and a 309-amino acid catalytic domain. This protein shows 44 and 40% similarity to rat procarboxypeptidase B and human mast cell procarboxypeptidase A, respectively. The residues critical for catalysis and zinc and substrate binding of carboxypeptidase A and B are conserved in the Mr 60,000 plasminogen-binding protein. The presence of aspartic acid at position 257 of the catalytic domain suggests that this protein is a basic carboxypeptidase. When activated by trypsin, it hydrolyzes carboxypeptidase B substrates, hippuryl-Arg and hippuryl-Lys, but not carboxypeptidase A substrates, and it is inhibited by the specific carboxypeptidase B inhibitor (DL-5-guanidinoethyl)mercaptosuccinic acid. We propose that the Mr 60,000 plasminogen-binding protein isolated here is a novel human plasma carboxypeptidase B and that it be designated pCPB.
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PMID:Isolation, molecular cloning, and partial characterization of a novel carboxypeptidase B from human plasma. 193 7

The characteristics of the acute and late human response to antigen in the upper and lower airways and in the skin is summarized in TABLE 2. This table makes it clear that while mast cells are responsible for the mediator release of the acute phase, eosinophils and basophils are the cells involved in the mediator release which occurs during the experimental late phase reaction. The pattern of mediators observed during the acute response is quite characteristic of the mast cell. Thus, in the nose, skin, and lungs, the acute response is characterized by significant increases in histamine, PGD2, tryptase, and sometimes LTC4. In the late phase reaction, the pattern of mediator release is characteristic of basophils and eosinophils, and includes histamine, LTC4 (where measurable), and eosinophil-derived proteins, without PGD2 or tryptase. Basophils have been identified at appropriate time-points in each model using morphologic and phenotypic criteria, and their numbers relate to the histamine levels. Finally, treatment with glucocorticosteroids, the most potent drugs available for treating chronic allergic inflammation, obliterates the late phase reaction and decreases both mediator release and the infiltration of eosinophils and basophils. Chronic allergic inflammation is now taken by both the pulmonary and immunologic community as a hallmark of asthma, and it can be stated without equivocation that the basophils are responsible for the mediator release observed in that response.
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PMID:The role of basophils in asthma. 195 78

The activation of mast cells is generally considered to be an important trigger mechanism in the immediate allergic response. This study focused on the determination of three markers of mast cell activation after an allergen challenge. Nasal allergen challenges were performed in 25 subjects with seasonal allergic rhinitis using three allergen doses increasing in 10-fold steps in a standardised nasal lavage model for the subsequent recovery of the markers of mast cell activation. The levels of histamine and tryptase in the nasal lavage fluid were determined using radioimmunoassays, while the TAME-esterase activity was determined using a radiochemical technique. The nasal symptoms obtained on challenge were assessed using a scoring technique. The allergen challenge resulted in significant increases in the levels of all three markers, tryptase, histamine and TAME-esterase. In the individual measurements after the challenges there was a highly significant correlation between the TAME-esterase levels and the tryptase levels (r = 0.71; P less than 0.001), while the generation of histamine and tryptase was not significantly correlated. When comparing the cumulative generation of the three markers, significant correlations were found between all three. Allergen challenges in six non-allergic controls using the same technique did not result in any increase in tryptase levels. The findings suggest that the determination of tryptase in nasal lavage fluid may be a valuable indicator of mast cell activation in the upper airways.
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PMID:Tryptase in nasal lavage fluid after local allergen challenge. Relationship to histamine levels and TAME-esterase activity. 195 95

Mast cell degranulation in the gut causes mucus secretion, mucosal edema, and increased gut permeability and may be responsible for some of the symptoms and signs of inflammatory bowel disease. We have used a novel monoclonal antibody (AAI) against tryptase expressed exclusively in the granules of mast cells to enumerate mast cells in rectal biopsies in order to study the effect of inflammatory bowel disease and drug treatment upon rectal mast cell numbers. Rectal mast cell numbers are significantly reduced in inflammatory bowel disease patients taking corticosteroids (mean 4.95 cells/mm2) when compared with control patients (10.1, P less than 0.001) and inflammatory bowel disease patients not taking corticosteroids (9.7, P less than 0.001 Wilcoxon rank sum test). The reduction in mast cell counts was independent of the degree of inflammation or architectural distortion. There was a negative correlation between the dose of corticosteroids and mast cell count (r = 0.53, P less than 0.05 Spearman rank correlation), and the mast cell count was reduced within a few days of treatment and remained low throughout steroid therapy. Mucosal mast cell depletion may be an important mechanism of action of corticosteroids in inflammatory bowel disease.
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PMID:Corticosteroid treatment reduces mast cell numbers in inflammatory bowel disease. 197 67

Systemic mastocytosis is characterized by an abnormal proliferation of tissue mast cells. Symptoms of mastocytosis are primarily attributed to the release of mast cell mediators during episodes of systemic activation of the excessive numbers of mast cells. Thus, biochemical evidence for the release of increased quantities of mast cell secretory products can suggest or confirm, depending on the clinical situation, a diagnosis of systemic mastocytosis. A major advantage of the biochemical approach to the diagnosis of systemic mast cell disease is that it has allowed the recognition of a class of patients in whom episodes of systemic mastocytes activation can be unequivocally documented biochemically but in whom clear-cut evidence of abnormal mast cell proliferation is lacking by current histologic criteria. Although the release of increased quantities of mast cell mediators can be demonstrated during episodes of mast cell activation in such patients, mediator levels are usually normal at quiescent times. By contrast, patients with proliferative mast cell disease (mastocytosis) usually exhibit chronic overproduction of mast cell mediators. Mast cell secretory products that can be measured in an attempt to obtain biochemical evidence of systemic mast cell activation include histamine, prostaglandin D2, tryptase, and heparin. The analytical approaches to assessing release of those individual mast cell products are evaluated. In general, the diagnosis and investigation of patients with systemic mast cell activation can best be accomplished by concerted use of histologic examination of key tissues together with analysis of chemical markers of the mast cell.
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PMID:Biochemical diagnosis of systemic mast cell disorders. 200 47

A solid phase immunoradiometric assay was developed for the quantitation of tryptase released from activated human mast cells. Tryptase exhibits a linear dose-response curve over the standard range of 2-50 micrograms/l in buffer, serum, and plasma. The dose-response curve approached a plateau at a tryptase concentration of 100 micrograms/l and exhibited partial inhibition at concentrations above 10,000 micrograms/l. The sensitivity of the assay was 0.2-0.4 micrograms/l, and the intra-assay and interassay coefficients of variation were below 4% at 2 micrograms/l or higher tryptase concentrations. The recovery of known amounts of purified tryptase added to serum ranged from 91 to 115%. Detection of tryptase was evaluated with several body fluids and was accurate in sera, plasma, bronchoalveolar lavage fluid, nasal lavage fluid, and saliva. The concentration of tryptase was examined in serum samples from 100 healthy controls; in each case the level was less than 2 micrograms/l. The immunoassay also was utilized to examine serum levels of tryptase after the onset of a hypotensive reaction in one patient receiving general anesthesia. A maximally elevated level of tryptase (25 micrograms/l) was detected at the first time point, 0.5 h, and elevated levels persisted to 6 h before a return to normal levels was documented at 24 h. Thus, the involvement of mast cell activation in hypotensive subjects can be ascertained by this new tryptase radioimmunoassay.
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PMID:A new radioimmunoassay for human mast cell tryptase using monoclonal antibodies. 201 45

Recent studies have led to a rapid expansion of knowledge concerning the structure and biology of the two major mast cell proteinases, tryptase and chymase. Tryptase is an abundant, trypsin-like enzyme found in the secretory granules of all human lung mast cells. The subunits of the heparin-associated tryptase tetramer appear to be the products of a multigene family whose intron-exon organization is unique and is not closely related to that of other mast cell or leukocyte serine proteinases. In vitro studies suggest that tryptases may participate in lung and airway responses by regulating airway neuropeptide activity, bronchomotor tone, and fibroblast mitogenesis. Mast cell chymases are chymotrypsin-like proteinases related closely to neutrophil cathepsin G and lymphocyte granzymes. The cDNA-derived structures of tryptase and chymase suggest that the two enzymes may differ in modes of activation from proenzyme forms, although the mature enzymes are packaged and released together. Chymase expression appears to be limited to a subset of human lung mast cells most prevalent in the airway submucosa. Possible roles for chymase include inactivation of sensory neuropeptides, regulation of submucosal gland secretion, and potentiation of histamine-induced vascular permeability.
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PMID:The structure and airway biology of mast cell proteinases. 202 78

A high-performance liquid chromatographic method involving fluorescence derivatization followed by separation on a reversed-phase polymer (octadecylated polyvinylalcohol copolymer gel) column is described for the determination of opioid peptides in rat brain tissues. The peptides extracted from brain tissues were converted into fluorescent derivatives by reaction with hydroxylamine, cobalt(II) ion and borate. The derivatives were separated on an Asahipak ODP-50 column by gradient elution of acetonitrile in the mobile phase containing borate buffer (pH 9.5). The detection limits (S/N = 3) for the peptides were 0.33-1.21 pmol per 100 microliters injected. The method actually permit the determination of leucine enkephalin, methionine enkephalin, methionine enkephalin-Arg-Phe and methionine enkephalin-Arg-Gly-Leu in the tissues. The method is also applied to the characterization of the peptides in the tissues by means of enzymatic degradations with carboxypeptidase A and trypsin.
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PMID:Pre-column fluorescence derivatization high-performance liquid chromatography of opioid peptides in rat brain and its use for enzymatic peptide characterization. 204 96

Two murine mAb were prepared against human mast cell carboxypeptidase (HMC-CP) purified from human skin, and were termed CP1 and CP2, respectively. Double immunohistochemical labeling of Carnoy's-fixed sections of human skin, lung, and gastrointestinal tissue with CP1 and CP2, respectively, and with a murine monoclonal antitryptase antibody demonstrated that HMC-CP was selectively present in a subset of human mast cells. Double labeling experiments with CP1 and CP2, respectively, and a murine anti-chymase mAb demonstrated the presence of HMC-CP in the tryptase-positive, chymase-positive mast cell type (MCTC) only. Immunohistochemical labeling of peripheral blood leukocytes resulted in staining of monocytes with CP2 but not with CP1. In addition to chymase and a cathepsin-G like proteinase, HMC-CP is another neutral protease that is selectively present in the MCTC tryptase-positive, chymase-positive mast cells type of mast cell, thus extending the biochemical definition of human mast cell heterogeneity.
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PMID:Human mast cell carboxypeptidase. Selective localization to MCTC cells. 205 Oct 21


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