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)

Active tumor promoters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or membrane-diffusible synthetic diacylglycerols such as 1,2-dioctanoyl-sn-glycerol (DiC8), which specifically activate protein kinase C (PKC), inhibited the agonist-mediated rise in cytosolic calcium [(Ca2+)i] in a mast cell line (PB-3c) and human platelets. TPA inhibition of agonist-mediated calcium transient in platelets was readily reversed by the PKC inhibitor staurosporine. In contrast to DiCs, only active tumor promoters induced a time- and dose-dependent translocation of cytosolic PKC to membranes as determined both enzymatically or by immunoblotting. However, the concentration of TPA required to induce a half-maximal subcellular redistribution of immunodetectable PKC activity was an order of magnitude greater than the half-maximal dose required to inhibit the intracellular rise in (Ca2+)i. Thus, activation of PKC seems not to be exclusively coupled to its translocation to membranes, suggesting that translocation of PKC is mainly involved in the down-regulation of PKC. Down-regulation of immunoprecipitable PKC was studied in various human breast cancer cell lines that display differential growth inhibitory responses toward the tumor promoter. TPA induced translocation of [35S]methionine-prelabeled cytosolic 80 kDa PKC to membranes followed by complete degradation of the enzyme (t1/2 = 2 h) without affecting PKC synthesis. During prolonged TPA exposure, 20-80% of total 80 kDa PKC of control cells was still synthetized as a membrane-bound 74/80 kDa PKC doublet. Although both proteins lacked PKC activity and phorbol ester binding, they revealed structural similarity with the active 80 kDa PKC form of untreated cells.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Role of protein kinase C (PKC) in short- and long-term cellular responses: inhibition of agonist-mediated calcium transients and down-regulation of PKC. 246 82

Autocrine interleukin 3 (IL-3)-secreting tumors were generated from an IL-3-dependent mouse mast cell line (PB-3c) after introduction of the v-H-ras oncogene. Tumor progression was characterized by four distinct phenotypes. The first corresponded to immortalized mast cells unresponsive to the oncogenic effect of v-H-ras. The second was expressed in a clonable subpopulation of PB-3c cells and was marked by the competence to form v-H-ras-dependent tumors (immortalized transformation competence). The third was a direct effect of v-H-ras expression on all PB-3c cells and was characterized in vitro by a reduced IL-3 requirement. Upon injection of v-H-ras-expressing, transformation-competent cells into mice, the final, fully malignant phenotype developed with a long latency period and was marked in vitro by independence of exogenous IL-3 and by autocrine IL-3 stimulation. Northern (RNA) blot analysis and an RNase A-T1 protection assay showed that IL-3 production was strictly associated with the tumor phenotype. Two of six tumors showed an alteration at the 5' region of the IL-3 gene. We conclude that v-H-ras required complementation by IL-3 gene rearrangement or an alternate event to generate autocrine mastocytomas.
 ...
PMID:A v-H-ras-dependent hemopoietic tumor model involving progression from a clonal stage of transformation competence to autocrine interleukin 3 production. 249 44

Ten tumors from 7 dogs were analyzed for estrogen receptors. Of 9 determined to be mast cell tumors, 6 were determined not to have estrogen receptors (less than 3 fmol of estradiol/mg of cytosol protein) and 3 were questionable (3 to 10 fmol of estradiol/mg). One tumor was a mixed mammary tumor and was determined to have estrogen receptors (12 fmol of estradiol/mg). Histologic grading of the mast cell tumors did not suggest a correlation with estrogen receptor values.
 ...
PMID:Evaluation of canine mast cell tumors for presence of estrogen receptors. 250 16

When applied to the skin, phorbol esters (PEs) elicit signs of acute inflammation, suggesting they may induce the release of mediators from mast cells. Therefore, we have studied the effects of PEs on purified rat peritoneal and thoracic mast cells both alone and in conjunction with the calcium ionophore, A23187, and various other secretagogues that interact with immunoglobulin E (e.g., anti-IgE and Con A) or other cell surface receptors, e.g., somatostatin and compd 48/80. PEs alone caused little or no release of histamine. However, the PE 12-O-tetradecanoylphorbol-13-acetate (TPA, 10 ng/ml) tremendously potentiated release induced by the calcium ionophore A23187, reducing the EC50 for A23187 from 832 ng/ml to 56 ng/ml. In the presence of suboptimal A23187 (50 ng/ml), only active tumor promoting PEs elicited histamine release. The EC50 values of the various active PEs were: TPA 5 ng/ml; 4 beta-PDD, 83 ng/ml; and 4-O-methyl-TPA, 807 ng/ml, with maximal histamine release ranging from 54 to 80%. TPA synergistically enhanced stimulation of histamine release by anti-IgE and Con A over the entire concentration-response range. In contrast, this synergism was absent when cells were stimulated with somatostatin and compd 48/80. Phorbol esters may act by increasing the activity of a calcium/phospholipid-dependent protein kinase (Ca/PL-PK). Mast cells do have Ca/PL-PK activity, and TPA in the presence of suboptimal A23187 induces protein phosphorylation comparable with other secretagogues. These results suggest that in the purified mast cell, PE-induced mediator release increases the sensitivity of release mechanisms for calcium, acts syngergistically with secretagogues interacting with IgE, and as suggested from structure-activity relationships, occurs via a specific mechanism of action perhaps involving the Ca/PL-PK.
 ...
PMID:Characterization of the effects of phorbol esters on rat mast cell secretion. 257 54

The recent identification of a T-cell-derived antigen-binding molecule (TABM), Trichinella spiralis factor (Tric-F), isolated from culture supernatants of lymphoid cells from mice infected with the intestinal helminth T. spiralis, has led to investigation of the ability of Tric-F to induce a T-cell-dependent feedback circuit that ultimately suppresses the production of other TABMs with similar (isotype-like) features. This form of regulation that has been identified in contact hypersensitivity and in delayed-type hypersensitivity (DTH) responses to tumor cells, was shown not to be antigen-specific but to be DTH-specific. Injection of mice with the TABM called picryl chloride factor (PCl-F) induced suppression of the production of DTH-initiating TABMs of other antigenic specificities. In this study, we report that intravenous injection of mice with Tric-F or PCl-F, 8 days before an oral infection with T. spiralis, induced suppressor cells that inhibited the T-cell-dependent influx into the gut of inflammatory cells, comprising mast cells and eosinophils. Similar results were obtained when the mice were skin sensitized with PCl 8 days prior to a T. spiralis infection, i.e. in a system where TABMs are known to be produced. The phenotype of these suppressor cells was Lyt-1-2+. This suppression preferentially affected the parasite-induced DTH-like response in the gut. In contrast, increased levels of IgA plasma cells in the gut, and worm expulsion were not affected by these treatments. In reciprocal experiments, intravenous injection of Tric-F, or PCl-F, or an oral infection with T. spiralis (that results in the production of TABMs) given 8 days before contact sensitizing mice with PCl, resulted in a suppression of elicitation of cutaneous DTH, as measured by ear swelling. In contrast, pretreatment with anti-dinitrophenyl IgE antibody did not interfere with intestinal inflammation to T. spiralis nor with DTH to PCl. Our results suggest that similar to cutaneous DTH, T. spiralis-specific T-cell factors are involved in the initiation and regulation of the DTH-like mast cell and eosinophil-rich intestinal inflammation that accompanies T. spiralis infections in the gut. Since both Tric-F and PCl-F induce suppression of cellular immune responses in vivo, independent of antigen specificity, it is concluded that Tric-F belongs to the same isotype of TABMs as PCl-F that therefore can be regulated by a non-antigen-specific, isotype-like, T-cell-dependent feedback mechanism.
 ...
PMID:Antigen-specific T-cell factors induce isotype-like suppression of mast cell and eosinophil-rich T-cell-dependent inflammation in the intestine of mice infected with Trichinella spiralis. 258 51

The histology of 17 cases of basal cell carcinoma and dermis next to the carcinoma was observed. The results showed that the mast cell number was markedly increased in the dermis near the basal cell carcinoma. There was an increase in the collagen fibers between the carcinoma and dermis tissues, forming a thin membrane around the carcinoma tissue. These findings suggest that the carcinoma-associated antigen may activate the lymphocytes to produce certain lymphokine which stimulates the proliferation and differentiation of the mast cell precursors. Histamine and other active mediators released from mast cells stimulate fibroblasts to synthesize collagen fibers which form a thin membrane between the carcinoma and dermis. The membrane plays a protective role against tumor dissemination.
 ...
PMID:[Basal cell carcinoma and mast cells]. 263 34

Although the association of malignancies and systemic mast cell disease (SMCD) is well established, the nature of this relationship is poorly understood. The observation of 19 malignancies in 17 of 60 patients with SMCD raised several questions regarding the chronological relationship of onset of SMCD and the malignancies, whether these patients are at increased risk for developing malignancy, and whether the distribution of solid vs hematologic malignancies indicates a relationship between SMCD and a particular tumor. The following malignancies were observed: eight solid tumors, seven acute nonlymphocytic leukemias, three malignant lymphomas, and one refractory anemia with excess blasts in transformation. The majority (13/17) of patients were found to have malignancies before, or within 12 months of, SMCD diagnosis. Statistical analysis suggested that patients with SMCD are not at increased risk for malignancies subsequent to the diagnosis of SMCD. The varied types of solid malignancies observed indicated a random distribution, in contrast to the hematologic malignancies that appeared to primarily affect the myeloid cells.
 ...
PMID:Solid and hematologic malignancies in 60 patients with systemic mast cell disease. 265 Jun 53

Post 5-fluorouracil-treated murine marrow cells were infected with a retroviral vector (MPZen) bearing a multi-potential colony stimulating factor (Multi-CSF) cDNA insert and then transplanted into lethally irradiated syngeneic recipients to study the effects of autocrine production of Multi-CSF in normal hematopoietic cells. Extremely high levels (14,000 U/mL) of Multi-CSF were detected in the sera and in media conditioned by various hematopoietic tissues of the transplanted animals. While spleen, peritoneal, and peripheral blood cellularity increased approximately 10-fold, 10-fold, and 50-fold, respectively, bone marrow cellularity decreased twofold. Progenitor numbers were depressed twofold in the bone marrow but elevated more than 100-fold in the spleen and peritoneum. The majority (80%) of transplanted mice died within 5 weeks of transplantation and showed extensive neutrophilic infiltration of the spleen, lung, liver, and muscle, often with mast cell foci; a phenomenon also seen in the skin and intestine. Neither the infected cells from hematopoietic tissues of the primary mice, nor autonomous mast cell-lines that grew from these cells in liquid culture produced any overt disease when transplanted into normal or sublethally irradiated secondary recipients. In contrast, injection into mice of autonomous FDC-P1 cells transformed by the same retroviral construct led to tumor formation in vivo within 4 weeks. Thus, dysregulated Multi-CSF expression by normal hematopoietic cells produces a fatal but nonneoplastic myeloproliferative syndrome.
 ...
PMID:Nonneoplastic hematopoietic myeloproliferative syndrome induced by dysregulated multi-CSF (IL-3) expression. 265 57

It has been suggested that Ag-specific T cell factors play a role in the early phase of cellular immune responses. Two of these factors are studied in this paper. The first factor is specific macrophage arming factor (SMAF), that binds to (arms) macrophages and renders them specifically cytotoxic against tumor cells. The second factor is involved in the induction of an early (2 h) mast cell-dependent hypersensitivity reaction, that precedes the delayed-type hypersensitivity response (mast cell arming T cell factor; MTCF). In this study we compare both factors in an allogeneic murine tumor system (C57BL (H-2b) mice sensitized against SL2 (H-2d) lymphoma cells), both factors were: 1) dependent on T lymphocytes for their production, 2) detectable in serum 2 to 3 days after immunization, and 3) MHC (H-2)-Ag specific. Immunochemical studies showed that both factors have a molecular mass between 45 and 90 kDa and bind to the mAb 14-30 (directed against specific T cell factors), but not to anti-kappa/lambda L chain antibodies. Furthermore, it was shown that SMAF produced in vitro could induce a mast cell-dependent early 2-h hypersensitivity reaction against SL2 tumor cells, and resembled in this way MTCF. We concluded that the biologic activities and immunochemical characteristics of SMAF and MTCF are similar. Both factors are produced during the early stages of the immune response and seem to play a role in the initiation of the cell-mediated immune response.
 ...
PMID:Two specific T cell factors that initiate immune responses in murine allograft systems. A comparison of biologic functions. 265 69

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.
 ...
PMID:Natural cytotoxic activity in a cloned natural killer cell line is mediated by tumor necrosis factor. 276 50


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>