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)

Derivatives of the antiallergic drug cromolyn [disodium 5,5'-[(2-hydroxy-1,3-propanediyl)-bis(oxy)]bis [4-oxo-(4H-1-benzopyran)-2- carboxylate]], which can be conjugated covalently at the propane 2-position to macromolecules and to insoluble matrices, were synthesized. Conjugates of these derivatives with macromolecules were examined for their binding to cells of the rat basophilic leukemia line RBL-2H3, which is widely employed as a model for immunologically induced mast cell degranulation. Only those drug-protein conjugates in which the cromolyn analogue with an amino group at the propane 2-carbon instead of the hydroxyl was linked to the carrier by glutaraldehyde were found to exhibit specific and saturable binding to these cells. Analysis of the binding data for these conjugates yielded an apparent binding constant of 3.8 +/- 0.2 X 10(8) M-1 and an apparent number of binding sites for the probe of 4000-8000 per cell. The conjugates found to bind specifically to the cells were also immobilized on agarose matrices and employed in an affinity-based isolation of the membrane component responsible for the observed binding. A single labeled polypeptide was eluted from these columns, onto which either whole cell lysates or solubilized purified plasma membranes of surface-radioiodinated RBL-2H3 cells had been adsorbed. This membrane protein appears on autoradiograms of nonreducing SDS-PAGE as a single broad band of approximately 110,000 daltons (Da) apparent molecular mass. On autoradiograms of reducing gels, the only band detected has an apparent mass of approximately 50,000 Da and appears narrower. Elution of the columns with the drug and disulfide-reducing agents or with the latter alone resulted in significantly higher yields of the 50-kDa polypeptide. Both the intact and reduced proteins bind strongly to immobilized concanavalin A and less so to immobilized wheat germ agglutinin, suggesting that the isolated intact protein is probably a dimer of two glycosylated subunits of similar molecular mass. Treatment of the reduced protein with endoglycosidase F leads to a decrease in its apparent molecular mass by approximately 12 kDa, suggesting that the extent of glycosylation of this polypeptide is approximately 25%. As shown in the following paper, the intact protein constitutes a Ca2+ channel that is activated upon IgE-Fc epsilon receptor aggregation.
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PMID:Isolation and purification of an Fc epsilon receptor activated ion channel from the rat mast cell line RBL-2H3. 246 4

Various human lymphokines such as semipurified human interleukin 3 (IL 3), recombinant human IL 3, granulocyte colony stimulating factor (G-CSF), and recombinant human interleukin 4 (IL 4) stimulated growth of human bone marrow cells, but from all these factors tested, only IL 3 by itself was able to cause an increase in histamine content. Fibroblast monolayers as well as factors in their supernatants also increased proliferation and histamine content of bone marrow cells. Concentrated supernatants (Mr greater than 10,000) also inhibited cell proliferation and induced histamine content. The same fraction concentrated on a Mr cut-off greater than 50,000 enhanced cell growth and the total histamine content per culture. Thus, fibroblast supernatants contained both growth promoting and inhibitory factors. However, using the rat basophilic leukemia (RBL) cell line as a test system for such fibroblast-derived differentiation factors, we showed that if cell proliferation was inhibited, histamine content was also enhanced. Furthermore, certain drugs known to inhibit cell division, such as sodium butyrate or hydroxyurea, were also found to cause an increase in histamine content of RBL cells. Thus, our data demonstrate that basophil/mast cell differentiation, in terms of augmentation of cellular histamine levels, may be achieved by exposure to certain growth-inducing cytokines, factors inhibiting proliferation or pharmacological agents which inhibit cell proliferation.
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PMID:Factors influencing proliferation and histamine content of cultured human bone marrow cells. 247 28

We have isolated and characterized the gene coding for the alpha subunit of the rat mast cell high affinity IgE receptor. The gene comprises five exons and four introns and spans approximately 6.6 kilobases. The leader sequence is encoded by two exons, the second of which is only 21 base pairs long. The third and fourth exons each code for repeating immunoglobulin-like extracellular domains. A hydrophobic transmembrane domain and positively charged cytoplasmic tail are encoded by a single final exon. The sequence of the 5'-flanking region was determined, and the major transcription initiation site was mapped. The structure of the gene suggests that two minor species of RNA produced by rat basophilic leukemia cells are due to alternative splicing. In one case, the small second exon is removed entirely, and, in the other, 163 base pairs at the 3' end of the fourth exon are removed. The latter species of RNA suggests the possibility of a secreted form of the alpha chain of the receptor. A third variant species of RNA, lacking a leader sequence, may be due to use of an alternative transcription initiation site.
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PMID:The gene for the rat mast cell high affinity IgE receptor alpha chain. Structure and alternative mRNA splicing patterns. 252 41

Bone marrow trephines from 31 patients with an initial diagnosis of myelodysplastic syndromes (MDS) were examined and analyzed histologically and immunohistochemically. In those cases terminating in overt leukemia (6/31, 19%), the number of bone marrow mast cells was significantly reduced, compared with those which did not evolve to overt leukemia. The bone marrow lymphoid cells that may participate in immunosurveillance against the proliferation of blast cells were also significantly reduced in cases terminating in overt leukemia. However, S-100 protein-positive cells, which include histiocytes and suppressor T-cells, were increased in cases terminating in overt leukemia. The results indicated that examination of the bone marrow to determine the proportions of mast cells and lymphoid cells which may be involved in host defense systems may be useful in predicting the evolution to overt leukemia in MDS. In the present series, patients with a hypocellular marrow (5/31, 16%) did not progress to overt leukemia and had a significantly lower bone marrow reticulin content, a significantly lower megakaryocyte count, a relatively higher mast cell count and a significantly higher lymphoid cell count than those with a normocellular or hypercellular marrow. These findings may reflect the initial features of MDS or, possibly, that hypocellular MDS is an independent entity with a low potential for blastic proliferation.
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PMID:Bone marrow analysis of the myelodysplastic syndromes: histological and immunohistochemical features related to the evolution of overt leukemia. 256 49

We report a case of systemic mastocytosis (SM) presenting as ascites and portal hypertension. The haematological picture at presentation was suggestive of chronic myelomonocytic leukaemia. Initial difficulties in making a diagnosis of SM were encountered as the cutaneous signs were atypical. The correct diagnosis was established only after tissue sections were appropriately stained for mast cells. The liver biopsy showed portal and sinusoidal mast cell infiltration, portal fibrosis and evidence of hepatic venous outflow obstruction. The disease progressed rapidly and recurrent massive ascites was a dominant problem. This case illustrates again the problems of making a diagnosis of SM especially when the clinical picture is atypical. Ascites as a presenting manifestation of SM has been reported previously in only six patients. Published cases of SM with portal hypertension or ascites or both are reviewed.
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PMID:Portal hypertension and ascites in systemic mastocytosis. 260 81

The rat mast cell protease gene, RMCP II, is specifically expressed in the mucosal subclass of rat mast cells. We show here that the 5'-flanking region of this gene contains a mast cell-specific enhancer that directs preferential expression of a linked reporter gene (human growth hormone) transfected into rat basophilic leukemia cells. A DNA fragment containing the enhancer sequence is capable of binding specifically to mast cell nuclear trans-acting factors. The sequence of this enhancer element contains a region of homology to a consensus core sequence present in the enhancer region of the pancreatic protease genes.
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PMID:The mast cell-specific expression of a protease gene, RMCP II, is regulated by an enhancer element that binds specifically to mast cell trans-acting factors. 264 95

The interleukin-2-dependent mouse natural killer (NK) cell line NKB61A2 concomitantly exhibits NK and natural cytotoxic (NC) activities. This was determined by the cells' ability to lyse both the NK-sensitive YAC-1 lymphoma and the NC-sensitive WEHI-164 fibrosarcoma cell lines in a 4- and 18-hour 51Cr release assay, respectively. Cell-free supernatant from NKB61A2 cells grown in culture for 48 h had substantial lytic activity against WEHI-164. The mouse mast cell line PT18-A17 and the rat basophilic leukemia cell line RBL-2H3, which both express NC activity, also produced a soluble factor during culture which lysed WEHI-164 cells. This activity was increased in the basophilic/mast cells by crossbridging the surface IgE receptors. Similar results were obtained by triggering the basophilic NC cells with the calcium ionophore ionomycin and the tumor promoter phorbol-12-myristate-13-acetate (PMA). Such triggering of NKB61A2 cells, however, did not significantly increase their NC activity. Interestingly, both ionomycin and PMA had an inhibitory effect on the NK activity of NKB61A2. Recently it has been found that tumor necrosis factor (TNF) is a major mediator of NC activity. To determine if the soluble factor responsible for the NC activity of the NK clone was related to TNF, a rabbit polyclonal antiserum to mouse TNF was tested against the cell-free culture medium of NKB61A2, PT18-A17, RBL-2H3 and murine recombinant TNF (Mu-rTNF). The lytic activity of the culture medium from all these cells and the Mu-rTNF control was abrogated by this antibody. These data suggest that the murine cell line NKB61A2 has both NK and NC activities and that the NC activity is due to a factor immunologically similar to TNF. In addition, the enhancement of NC activity in the NK cell line is apparently under control by a separate pathway, different from that in the basophilic cells.
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PMID:Natural cytotoxic activity in a cloned natural killer cell line is mediated by tumor necrosis factor. 276 50

Interleukin-3-dependent hematopoietic stem cells commonly accumulate in spleens of mice infected with leukemia viruses. To study their origins, a molecularly tagged helper-free Friend spleen focus-forming virus was used to produce erythroleukemias. Uninfected interleukin-3-dependent basophil-mast cell progenitors coproliferated amidst the spleen focus-forming virus-infected leukemic cells. Splenic proliferation of normal stem cells is apparently a host response to leukemogenesis, and we propose that it may contribute to certain retroviral diseases.
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PMID:Splenic accumulation of interleukin-3-dependent hematopoietic cells in Friend erythroleukemia. 278 94

Mouse cell lines of different lineages have been established which constitutively secrete large quantities of recombinant mouse interleukins (mIL2, mIL3, mIL4 or mIL5). An existing bovine papilloma virus-based expression vector, pBV-1MTHA, was modified to allow transformed X63Ag8-653 myeloma cells, NIH 3T3 fibroblasts and C127 mammary tumor cells to stably carry multiple copies of the vector, to express the inserted cDNA encoding a single interleukin constitutively, and to secrete the interleukin in high quantities. Cell lines transformed with mIL2 cDNA stably carried 30-100 copies of the plasmid per cell and constitutively secreted biologically active mIL2 in quantities similar to those produced by murine EL4 thymoma cells or rat spleen cells stimulated with mitogens. Deletion of the 3' untranslated region containing AT-rich sequences from the mIL2 cDNA resulted in a 100-fold increase in the constitutive production and secretion of mIL2 by the transformants. Addition of a heavy metal further increased the production 2 to 6-fold. Cells transformed with 3'-deleted mIL3 cDNA constitutively secreted 300-1000 times higher activities of mIL3 than the myelomonocytic leukemia line WEHI3. mIL4 produced by the similar transformants induced [3H]thymidine uptake of a T cell line, a mast cell line and B leukemia cells, and enhanced the production of IgG1 by B cells. IL4 titers were 150 times higher than those produced by the concanavalin A-stimulated T cell line 2.19. mIL5 was secreted by similar transformants at 10-fold higher titers than those produced by concanavalin A-stimulated 2.19 T cells, as judged by the proliferation and maturation of B cell leukemia BCL1. The expression vectors should be useful in establishing eukaryotic cell lines producing proteins from full length cDNA clones at higher rates. The established cell lines secreting IL2, 3, 4 or 5 at high rate should be useful sources for these interleukins in the investigation of their function in the immune system.
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PMID:Establishment of mouse cell lines which constitutively secrete large quantities of interleukin 2, 3, 4 or 5, using modified cDNA expression vectors. 283 Oct 66

Bone marrow-derived leukocytes of murine epidermis can express two phenotypes: typical Langerhans cells, which are Ia+ and Thy-1-, and a recently discovered second population that is Thy-1+ and Ia-. To verify that these phenotypes are expressed by two different cell types, and to help understand their lineage and function, we have studied morphology and reactivity with a large panel of antibodies. Dual antibody immunofluorescence combined with electron microscopy showed that Thy-1+ and Ia+ cells were each distributed in a regular fashion and formed adjacent dendritic systems in or close to the basal layer. Double-labeling studies with anti-Ia and a second monoclonal antibody revealed that all Langerhans cells expressed F4/80 (macrophage), Mac-1 (C3bi receptor), and 2.4G2 (Fc receptor), as well as the thymus leukemia (TL) and heat-stable (M1.69/16) antigens. A large fraction expressed S100 and all exhibited membrane ATPase and nonspecific esterase. In contrast, Thy-1+ cells lacked all these features of Langerhans cells, except that a minority were strongly reactive with 2.4G2. Thy-1+ cells also lacked differentiation antigens of most other types of leukocytes, except they were rich in asialo GM1. By electron microscopy, Thy-1+ cells had cytoplasmic granules that were similar in structure and in their aryl sulfatase content to those previously described in natural killer cells. The granules were enlarged in beige mice, suggesting a lysosomal origin, and were present in mast cell-deficient W/Wv mice, indicating no relation to mast cells. We conclude that Thy-1+ epidermal cells are thoroughly distinct from Langerhans cells. On the basis of morphology and phenotype, they may represent a type of tissue natural killer cell. Thy-1+ natural killer cells are now being identified in several nonlymphoid sites, such as gut epithelium and the livers of mice given adjuvants. If Thy-1+ epidermal cells prove to be natural killer cells, it is noteworthy that they represent a resident population regularly distributed in the basal layer of all mouse strains. The notion that Thy-1+ epidermal cells are immature natural killer cells is intriguing in light of recent evidence that Ia+ Langerhans cells are also immature with respect to accessory cell function. The epidermis may not have the functional capacities of a lymphoid organ, but it could contribute immature cells important for both natural and acquired resistance.
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PMID:The Thy-1-bearing cell of murine epidermis. A distinctive leukocyte perhaps related to natural killer cells. 286 Dec 45


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