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

The bovine exocrine pancreatic cell produces a variety of enzymes and proenzymes for export. Biochemical studies by Greene L.J., C.H. Hirs, and G.E. Palade (J. Biol. Chem. 1963. 238:2054) have shown that the mass proportions of several of these proteins in resting pancreatic juice and zymogen granule fractions are identical. In this study we have used immunocytochemical techniques at the electron microscope level to determine whether regional differences exist in the bovine gland with regard to production of individual secretory proteins and whether specialization of product handling occurs at the subcellular level. The technique used is a modification of one previously reported (McLean, J.D., and S.J. Singer. 1970. Proc. Natl. Acad. Sci U.S.A. 69:1771) in which immunocytochemical reagents are applied to thin sections of bovine serum albumin-imbedded tissue and zymogen granule fractions. A double antibody technique was used in which the first step consisted of rabbit F(ab')2 antibovine secretory protein and the detection step consisted of sheep (F(ab')2 antirabbit F(ab')2 conjugated to ferritin. The results showed that all exocrine cells in the gland, and all zymogen granules and Golgi cisternae in each cell, were qualitatively alike with regard to their content of secretory proteins examined (trypsinogen, chymotrypsinogen A, carboxypeptidase A, RNase, and DNase). The data suggest that these secretory proteins are transported through the cisternae of the Golgi complex where they are intermixed before copackaging in zymogen granules; passage through the Golgi complex is apparently obligatory for these (and likely all) secretory proteins, and is independent of extent of glycosylation, e.g., trypsinogen, a nonglycoprotein vs. DNase, a glycoprotein.
 ...
PMID:Immunocytochemical localization of secretory proteins in bovine pancreatic exocrine cells. 31

Mouse bone marrow-derived mast cells (BMMC) obtained by culturing progenitor cells with rIL-3 express mouse mast cell protease (MMCP)-5 mRNA but not MMCP-1 mRNA or MMCP-4 mRNA. In terms of mast cell differentiation, these transcripts encode one early-expressed and two late-expressed chymases, respectively. cDNA and cRNA probes were used in RNase protection assays and RNA blot analyses to study the expression of these three homologous protease genes in cultured mast cells and in helminth-infected mice. Intestinal tissue from Trichinella spiralis-infected mice, containing high numbers of mucosal mast cells, had abundant amounts of MMCP-1 mRNA but only minimal amounts of the serosal mast cell transcript that encodes MMCP-4. Exposure of mouse BMMC to rIL-10-induced transcription of the MMCP-1 gene but not the MMCP-4 gene, and a cDNA encoding MMCP-1 was obtained from these rIL-10-treated cells. The expression of MMCP-1 mRNA in BMMC depended on the continuous exposure of these cells to rIL-10, and the level of MMCP-1 mRNA (but not MMCP-5 mRNA) was substantially higher in BMMC maintained in rIL-4 and rIL-10 than in rIL-3 and rIL-10 or in rIL-3, rIL-4, and rIL-10. Thus, whereas rIL-3 elicits transcription of early expressed genes in cultured mast cells, it suppresses the transcription of late-expressed genes. These in vitro and in vivo transcription studies also indicate that rIL-10 preferentially induces differentiation of mouse progenitor cells in a mucosal mast cell-specific lineage, and that expression of granule serine protease genes is regulated in a subclass-specific manner in mouse mucosal mast cells and serosal mast cells.
 ...
PMID:IL-10 induces transcription of the gene for mouse mast cell protease-1, a serine protease preferentially expressed in mucosal mast cells of Trichinella spiralis-infected mice. 151 75

The pancreatic tissue of normal and virus-induced diabetic cattle was investigated by the indirect immunofluorescence technique. Seven secretory proteins (chymotrypsinogen A, trypsinogen, carboxypeptidase A, RNase, DNase, alpha-amylase and lipase) were localized in normal bovine pancreatic acinar cells but in diabetic animals amylase, lipase and carboxypeptidase were either not detectable or markedly diminished. Decrease in amylase content has been reported previously in other diabetic animals. The diminution of the three pancreatic enzymes may be related to the destruction of pancreatic endocrine tissue that occurs in these diabetic animals.
 ...
PMID:Alterations of exocrine pancreatic enzymes in virus-induced diabetic cattle as revealed by immunohistochemistry. 618 Sep 49

The Wsh is a mutant allele at the W (c-kit) locus of mice, but no significant abnormalities are found at the coding region of the Wsh allele. Since cultured mast cells derived from the spleen of Wsh/Wsh mice do not express messenger RNA (mRNA) of c-kit, we studied the interrelation between the number of mast cells and the magnitude of c-kit mRNA expression in the skin of Wsh/Wsh mice of various ages. The number of mast cells in the skin of Wsh/Wsh embryos of 18 days postcoitum (pc) was approximately 40% that of normal control (+/+) embryos, but the number of mast cells decreased exponentially after birth; the number dropped to 0.6% that of +/+ mice at day 150 after birth. A weak but apparent signal of c-kit mRNA was detectable in the skin of 18-day pc Wsh/Wsh embryos by RNase protection assay but not in the skin of 5-day-old Wsh/Wsh mice. The number of c-kit protein-containing cells was significantly greater in the skin of 18-day pc Wsh/Wsh embryos than in the skin of 5-day-old Wsh/Wsh mice. The abolishment of c-kit mRNA expression appeared to be specific, because the expression of mast cell carboxypeptidase A mRNA but not of c-kit mRNA was detectable by in situ hybridization in skin mast cells of 5-day-old Wsh/Wsh mice. Taken together, the expression of c-kit mRNA was abolished first, then the content of c-kit protein dropped to undetectable levels, and then the disappearance of Wsh/Wsh mast cells themselves followed.
 ...
PMID:C-kit gene is expressed by skin mast cells in embryos but not in puppies of Wsh/Wsh mice: age-dependent abolishment of c-kit gene expression. 751 15

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)
 ...
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.
 ...
PMID:Cloning of two adenosine receptor subtypes from mouse bone marrow-derived mast cells. 815 66

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.
 ...
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.
 ...
PMID:Ribonuclease-gold labels chondroitin sulphate in guinea pig basophil granules. 979 79

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.
 ...
PMID:Ribonuclease-gold labels proteoglycan-containing cytoplasmic granules and ribonucleic acid-containing organelles--a survey. 1021 22

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.
 ...
PMID:RNA is closely associated with human mast cell secretory granules, suggesting a role(s) for granules in synthetic processes. 1065 81


1 2 Next >>