Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular basis for the commitment of multipotential myeloid progenitors to the eosinophil lineage, and the transcriptional mechanisms by which eosinophil-specific genes are subsequently expressed and regulated during eosinophil development are currently unknown. Interleukin-5 (IL-5) is a T cell and mast cell-derived cytokine with actions restricted to the eosinophil and closely related basophil lineages in humans. The high affinity receptor for IL-5 (IL-5R) is composed of an alpha subunit (IL-5R alpha) expressed by the eosinophil lineage, that associates with a beta c subunit shared with the receptors for IL-3 and granulocyte-macrophage colony stimulating factor (GM-CSF). As a prerequisite to studies of the transcriptional regulation of the IL-5R alpha subunit gene, we used three different methods, including primer extension, RNase protection, and 5'-RACE to precisely map the transcriptional start site to a position 15 base pairs (bp) upstream of the 5' end of the published sequence of IL-5R alpha exon 1. To initially identify the IL-5R alpha promoter, 3.5 kilobases (kb) and 561 bp of the 5' sequence flanking the transcriptional start site were subcloned into the promoterless pXP2-luciferase vector. Transient transfection of these constructs into an eosinophil-committed HL-60 subline, clone HL-60-C15, induced the expression of approximately 240-fold greater luciferase activity than the promoterless vector, identifying a strong functionally active promoter region within the 561 bp of sequence proximal to the transcriptional start site and with activity equivalent to pXP2 constructs containing the entire 3.5 kb of upstream sequence. To more precisely localize the cis-acting regulatory elements in this region important for promoter activity, a series of 5' deletion mutants of the 561-bp region were generated in the pXP2-luciferase vector. Deletion of the region between bp -432 and -398 reduced promoter activity by more than 80% in the HL-60-C15 cell line. Further analyses of the activity of the IL-5R alpha promoter constructs in various other eosinophil, myeloid, and non-myeloid cell lines indicated that the promoter was relatively myeloid and eosinophil lineage-specific in its expression. Consensus sequences for known transcription factor binding sites were not present in the 34-bp region of the promoter required for maximal activity, suggesting unique myeloid- and possibly eosinophil-specific regulatory elements.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Identification and characterization of a functional promoter region in the human eosinophil IL-5 receptor alpha subunit gene. 783 16

Adenosine potentiates the stimulated release of mast cell mediators. Pharmacologic studies suggest the presence of two adenosine receptors, one positively coupled to adenylate cyclase and the other coupled to phospholipase C activation. To identify mast cell adenosine receptor subtypes, cDNAs for the A1 and A2a adenosine receptors were obtained by screening a mouse brain cDNA library with the use of PCR-derived probes. Mouse bone marrow-derived mast cell cDNA libraries were constructed and screened with the use of A1 and A2a cDNA probes, which revealed the presence of A2a, but not A1, receptor clones. A putative A2b receptor was identified by using low stringency mast cell library screening. Northern blotting of mast cell poly(A)+ RNA with the use of receptor subtype probes labeled single mRNA bands of 2.4 kb and 1.8 kb for the A2a and A2b receptors, respectively. In situ cells. An A2a receptor-specific agonist failed to enhance mast cell mediator release, which suggests that the secretory process is modulated through the A2b and/or another receptor subtype. By using RNase protection assays, we found that mast cells that had been cultured in the presence of N-ethylcarboxamidoadenosine for 24 h exhibited a decrease in both A2a and A2b receptor RNA levels. Cells that had been cultured for 1 to 2 days in the presence of dexamethasone demonstrated increased amounts of A2a receptor mRNA, but no identifiable change in A2b receptor mRNA. Mast cells possess at least two adenosine receptor subtypes that may be differentially regulated.
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PMID:Cloning of two adenosine receptor subtypes from mouse bone marrow-derived mast cells. 815 66

A bifidogenic growth stimulator was present in the cell-free filtrate of Propionibacterium freudenreichii 7025 culture and in the methanol extract fraction of the cells. Several intestinal bacteria, such as Bacteroides, Enterobacter, and Enterococcus, which also released a growth stimulator for bifidobacteria, may play an important role in regulation of a bifidobacterial population in colonic microflora. The water-soluble stimulator from the methanol extract of the cells was partially purified. The molecular weight of the stimulator appeared to be < 3000. The stimulatory activity was unaffected by treatments with pronase, carboxypeptidase A, ribonuclease, or nuclease P1 and was heat stable over a wide pH range. This stimulator differed from cyanocobalamin and from organic acids, such as acetate and propionate. Because it was stable to heat and proteolytic enzymes, the stimulator is a useful bifidogenic factor that can reach the large intestine while retaining its activity. Short-chain fatty acids were highly inhibitory to the growth of many intestinal bacteria, particularly Gram-negative facultative and obligatory anaerobes. The short-chain fatty acids (especially propionate) stimulated the growth of bifidobacteria. The growth of Bifidobacterium adolescentis 6003 was further enhanced in the presence of short-chain fatty acids and the stimulator produced by P. freudenreichii 7025. Viable counts of strain 6003 grown with Bacteroides vulgatus JCM 5826T increased more than 10(4) over those of the single culture of strain 6003. However, the growth of strain 6003 was inhibited in the mixed culture with Clostridium perfringens 7028. In continuous culture, the growth of bifidobacterial strain 6003 could be greatly enhanced, even in the presence of clostridial strain 7028, in media with short-chain fatty acids and stimulator produced by P. freudenreichii 7025.
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PMID:Growth stimulator for bifidobacteria produced by Propionibacterium freudenreichii and several intestinal bacteria. 818 63

We evaluated an enzyme affinity-gold ultrastructural technique designed to identify RNA-rich structures, based on an RNase-gold (R-G) probe in human mast cells (HMCs). As expected, the R-G technique labeled RNA-containing ribosomes and nucleoli in HMCs. The heparin-rich secretory granules in HMCs were also labeled. Extensive studies revealed that HMCs isolated from lung or skin and sustained in short-term cultures, derived de novo in growth factor-supplemented cord blood cell cultures, or present in vivo in multiple sites all shared this property. We performed a large number of controls designed to examine the HMC granule binding characteristics of gold alone, of irrelevant protein- or enzyme-gold reagents, of the role of charge and enzyme activity after various enzyme digestions, after blocking with macromolecules, after exposure to inhibitors of RNase, of heparin, or to irrelevant enzyme inhibitors, including staining of macromolecule-containing test agar blocks and a variety of combined absorption and digestion experiments of the binding of R-G to HMC granules. These studies established that the R-G method detected heparin in this site in conventionally prepared, well-preserved electron microscopic samples. These findings demonstrate a new use for this enzyme affinity-gold technique in mast cell biology, based on the known property of heparin as an inhibitor of RNase.
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PMID:Ribonuclease-gold labels heparin in human mast cell granules. New use for an ultrastructural enzyme affinity technique. 960 80

Basophilic leucocytes are metachromatic granule-containing secretory granulocytes that contain a mixture of granular proteoglycans devoid of heparin. In guinea pigs, isolated basophilic leucocyte granules primarily contain chondroitin sulphate. We have recently demonstrated that an enzyme-affinity-gold technique to image RNA, using the reagent RNase gold, also binds specifically to heparin in human mast cell granules. Such binding is based on the known property of heparin as a competitive inhibitor of RNase. Using similar methods, we show here that RNase-gold binds to the chondroitin sulphate in the secretory granules of guinea pig basophils, thus broadening the applicability of this post-embedding affinity-gold method to studies that require imaging of chondroitin sulphate in routinely prepared electron microscopical samples.
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PMID:Ribonuclease-gold labels chondroitin sulphate in guinea pig basophil granules. 979 79

Although mast cell secretion has been intensively studied because of its pivotal role in allergic reactions and its advantages as a physiologic model, the molecular composition of the secretory machine is virtually unknown. In view of the guanine-nucleotide dependency of mast cell exocytosis and the participation of Rab3 proteins in synaptic vesicle release, we hypothesized that a Rab3 isoform regulates mast cell secretion. Fragments of Rab3A, 3B, and 3D were cloned from RBL-2H3 mast cells by reverse transcription- polymerase chain reaction (RT-PCR). Northern blot analysis revealed Rab3D transcripts to be relatively abundant, Rab3B substantially less so, and Rab3A and 3C undetectable. By ribonuclease (RNase) protection assay, Rab3D transcripts were at least 10-fold more abundant than those of other isoforms, and by immunoblot analysis, Rab3D protein was at least 60-fold more abundant than that of Rab3B. Rab3D was more abundant in RBL cells than in brain, but the total mass of Rab3 proteins in RBL cells was 10-fold less than in brain. Rab3D only partly colocalized with secretory granules in RBL cells, but fully colocalized in mature peritoneal mast cells. There was a descending concentration gradient of Rab3D from peripheral to central granules, and no cytoplasmic pool was detectable in resting mast cells. Following exocytotic degranulation, Rab3D translocated to the plasma membrane and remained there for at least 15 min. These studies suggest that Rab3D is a component of the regulated exocytotic machine of mast cells, and identify differences between mast cells and neurons in Rab3 expression and trafficking.
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PMID:Rab3D, a small GTPase, is localized on mast cell secretory granules and translocates to the plasma membrane upon exocytosis. 987 Sep 20

An enzyme-affinity-gold method to detect RNA in routinely prepared ultrastructural samples is based on the affinity of the gold-coupled enzyme, ribonuclease, for its substrate, RNA. High concentrations of a known inhibitor of RNase, heparin, are uniquely located in human mast cell granules. Specific labeling for the presence of heparin in these structures was determined using the RNase-gold (R-G) reagent based on the RNase inhibitor property of heparin. This property was used to probe for the presence of proteoglycans (PG) known to be present in a wide variety of ultrastructural samples, none of which contain heparin. In addition to known subcellular sites of RNA, the R-G reagent was shown to bind to PG-rich cytoplasmic granules in a wide variety of leukocytes and secretory cells of epithelial, endocrine, and neuroendocrine origin. This newly recognized property was used to image the changing distribution of labeled PGs during cellular maturation, secretion, and recovery from secretion of secretory cells in vivo, ex vivo, in vitro and in isolated, biochemically defined guinea pig basophil granule preparations.
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PMID:Ribonuclease-gold labels proteoglycan-containing cytoplasmic granules and ribonucleic acid-containing organelles--a survey. 1021 22

The stem cell factor (SCF)/c-kit ligand/receptor system has been implicated in stem (oval) cell activation following liver injury in the rat. The aim of this study was to determine the role of the SCF/c-kit system in pediatric human liver during acute and chronic liver injury. Tissue was obtained from hepatectomy specimens of patients undergoing liver transplantation for extrahepatic biliary atresia (EHBA) and fulminant hepatic failure (FHF). Specific expression of mRNA for c-kit and beta-actin was measured by ribonuclease protection and by immunohistochemistry to localize c-kit in tissue sections. Expression of c-kit was detected at relatively consistent levels in normal and cirrhotic (EHBA) livers. However, in FHF, c-kit mRNA levels were elevated in 3 of 6 specimens. Immunolocalization highlighted the presence of small numbers of c-kit-positive cells in the portal tracts of normal livers with increased numbers in cirrhotic livers. The highest c-kit staining, however, was observed in FHF, in which, in addition to the cells in the portal tracts, discrete c-kit-positive cells were also found integrated into bile ducts. Colocalization studies demonstrated some of the c-kit-positive cells to be of mast cell, leukocyte, and hematopoietic cell origin. However, there remained a subset that was also negative for these markers. The up-regulation of c-kit receptor expression in diseased livers suggests an involvement of this receptor/ligand system in hepatic repair mechanisms, and we speculate that c-kit-positive cells may represent a hepatic progenitor cell population. The origin and growth/differentiation potential of these c-kit-positive cells is under investigation.
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PMID:Expression of the stem cell factor receptor c-kit in normal and diseased pediatric liver: identification of a human hepatic progenitor cell? 1038 46

The distribution of ribosomes in mature human mast cells, a major granulated secretory cell, does not resemble that in other secretory cells, such as pancreatic acinar cells and plasma cells. By routine ultrastructural analysis, ribosomes in human mast cells are often close to, attached to, or even appear to be within secretory granules. To document better these relationships, we used multiple electron microscopic imaging methods, based on different principles, to define RNA, ribosome, and granule relationships in mature human mast cells. These methods included EDTA regressive staining, RNase digestion, immunogold labeling of ribonucleoproteins or uridine, direct binding or binding after ultrastructural in situ hybridization of various polyuridine probes to polyadenine in mRNA, and ultrastructural autoradiographic localization of [3H]-uridine incorporated into cultured human mast cells. These different labeling methods demonstrated ribosomes, RNA, U1SnRNP (a small nuclear RNP specific for alternative splicing of mRNA), mRNA, and uridine to be associated with secretory granules in human mast cells, implicating granules in a larger synthetic role in mast cell biology.
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PMID:RNA is closely associated with human mast cell secretory granules, suggesting a role(s) for granules in synthetic processes. 1065 81

Borrelia burgdorferi, the spirochetal bacterium that causes human Lyme disease, encodes numerous lipoproteins which have the capacity to trigger the release of proinflammatory cytokines from a variety of host cell types, and it is generally believed that these cytokines contribute to the disease process in vivo. We previously reported that low-passage-number infectious B. burgdorferi spirochetes express a novel lipidation-independent activity which induces secretion of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) by the mouse MC/9 mast cell line. Using RNase protection assays, we determined that mast cells exposed in vitro to low-passage-number, but not high-passage-number, B. burgdorferi spirochetes show increased expression of additional mRNAs representing several chemokines, including macrophage-inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and TCA3, as well as the proinflammatory cytokine interleukin-6. Furthermore, mast cell TNF-alpha secretion can be inhibited by the phosphatidylinositol 3-kinase inhibitor wortmannin and also by preincubation with purified mouse immunoglobulin G1 (IgG1) and IgG2a, but not mouse IgG3, and by a mouse Fc gamma receptor II and III (FcgammaRII/III)-specific rat monoclonal antibody, suggesting the likely involvement of host FcgammaRIII in B. burgdorferi-mediated signaling. A role for passively adsorbed rabbit or bovine IgG or serum components in B. burgdorferi-mediated FcgammaR signaling was excluded in control experiments. These studies confirm that low-passage-number B. burgdorferi spirochetes express a novel activity which upregulates the expression of a variety of host cell chemokine and cytokine genes, and they also establish a novel antibody-independent role for FcgammaRs in transduction of activation signals by bacterial products.
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PMID:Role of Fc gamma receptors in triggering host cell activation and cytokine release by Borrelia burgdorferi. 1111 32


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