Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Phenylalanine methylester (PME), a lysosomotropic compound can be used to deplete monocytes and myeloid cells from peripheral blood and bone marrow (BM). The potential of PME for purging leukemic cells from BM was investigated using U937 and HL-60 cell lines as models. Optimal purging conditions for U937 cells were determined using an MTT assay (3-4, 5-dimethylthiazol-2, 5-diphenyl tetrazolium biomide; Sigma). Elimination of U937 cells was time-, temperature-, and dose-dependent. PME activity was optimal at 37 degrees C for 45 minutes. Depletion of U937 was > 2.8 logs for 50 mmol/L PME. Compared with another purging agent, 100 micrograms/mL 4-hydroperoxycyclophosphamide had activity comparable to 40 mmol/L PME. HL-60 cells were even more sensitive to PME than U937 cells. To support observations made with the MTT assay, clonogenic assays were performed. PME, 50 mmol/L at 37 degrees C resulted in total depletion (> 5 logs) of U937 colonies. Progressive depletion of normal progenitor cells occurred when BM was incubated with PME at concentrations from 5 to 100 mmol/L. At 37 degrees C, 50 mmol/L PME reduced colony-forming units-granulocyte-macrophage and burst-forming units-erythroid (BFU-E) recovery by 98%. Recombinant human mast cell factor augmented BFU-E after PME treatment but had no effect on HL-60 or U937. These studies suggest that PME deserves further study as an agent for ex vivo marrow purging.
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PMID:Potential of phenylalanine methylester as a bone marrow purging agent. 138 2

Although histamine is the principal mediator of the immediate allergic reaction, other inflammatory mediators as well as neuropeptides also contribute to rhinorrhea and nasal congestion. Within minutes of exposure to allergen, mast cells produce histamine, leukotriene C4, and prostaglandin D2. A concomitant increase occurs in neuropeptides and bradykinin. In vitro mast cell activation also leads to the release of tumor necrosis factor--alpha, several interleukins, and granulocyte-macrophage colony--stimulating factor. Because all these various mediators and neuropeptides may play a role in producing rhinorrhea and congestion, antihistamines alone cannot control all of the symptoms of allergic rhinitis. However, the combination of antihistamines with topical corticosteroids can inhibit the generation, release, and activity of most if not all of the mediators potentially involved in the allergic response.
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PMID:Mediators of allergic rhinitis. 140 52

We investigated the effects of interferon gamma (IFN-gamma) on the growth of murine hematopoietic progenitors. IFN-gamma inhibited granulocyte colony-stimulating factor (G-CSF)- and interleukin-3 (IL-3)-dependent colony growth by granulocyte-macrophage (GM) progenitors derived from the bone marrow cells of normal mice. However, the number of IL-3-dependent GM colonies formed by the bone marrow cells of 5-fluorouracil (5-FU)-treated mice was not influenced by the addition of IFN-gamma. Replating experiments suggested that IFN-gamma suppressed GM colony growth directly and that it exerted an inhibitory effect on the proliferation, but not on the commitment, of GM progenitors. In contrast, IFN-gamma failed to suppress colony growth by mast cell progenitors. Erythroid and megakaryocytic progenitors exhibited different responses to IFN-gamma depending on mouse strains. These results suggest that potent negative regulators are not always inhibitors of hematopoietic progenitors.
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PMID:Interferon-gamma inhibits proliferation, but not commitment, of murine granulocyte-macrophage progenitors. 144 13

Murine interleukin 9 (mIL-9) is a novel T-cell-derived lymphokine previously described as a T-cell growth factor (P40/TCGFIII) and as a mast cell growth-enhancing activity (MEA). In the present study we examined the potency of recombinant (r)mIL-9 to exhibit hemopoietic growth factor activity in the human system. In semisolid cultures of normal human bone marrow-derived mononuclear cells, rmIL-9 alone at a concentration range from 25 to 200 U/ml did not reveal any colony-stimulating activity on human granulocyte-macrophage colony-forming cells (GM-CFC), erythroid colony-forming units (CFU-E), and erythroid burst-forming units (BFU-E). Furthermore, we did not observe synergistic effects of rmIL-9 on the number, size, and morphological composition of human granulocyte-macrophage colonies in cultures stimulated with giant cell tumor-conditioned medium. However, a synergistic effect of rmIL-9 in the human erythropoietic culture system was clearly demonstrated in the presence of recombinant human erythropoietin (rhEpo). Recombinant murine IL-9 at a concentration of 200 U/ml enhanced the number of BFU-E-derived day-14 colonies about 3.6-fold as compared to control cultures stimulated with Epo alone. The formation of CFU-E-derived day-7 colonies was not significantly altered under the same conditions. Our results demonstrate that in the presence of rhEpo, rmIL-9 is synergistically active in human bone marrow cultures as an erythroid burst-promoting factor. The development of granulocyte-macrophage colonies obviously is not affected. This finding strongly suggests that mIL-9 can mediate signals via human IL-9 receptors and further extends the range of biological activities hitherto ascribed to mIL-9.
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PMID:Recombinant murine interleukin 9 enhances the erythropoietin-dependent colony formation of human BFU-E. 158 1

As elevated bronchoalveolar lavage (BAL) fluid histamine levels are noted in patients with pulmonary fibrosis (PF), we assayed BAL fluid from 16 patients with PF for the presence of a histamine releasing factor (HRF). HRF activity was assayed by measuring release of the preformed mast cell-derived mediators, histamine, or beta-hexosaminidase (beta-hex) from a purified population of IL-3 dependent mouse bone marrow derived mast cells (MBMMC) or human blood basophils. Mean BAL cell free histamine levels in the patients with PF was 1226 +/- 1349 pg/ml, whereas BAL histamine levels in a comparison group of six non-PF patients was 118 +/- 60 pg/ml. HRF was significantly elevated in BAL fluid of patients with PF (mean beta-hex release 24.5 +/- 12.9%; range 6.8 to 52.4%) compared to the non-PF group of patients (mean beta-hex release 7.9 +/- 7.7%; range 1.8 to 20.7%). The PF HRF not only degranulated MBMMC, but also induced the generation of the arachidonic acid metabolite leukotriene C4 from MBMMC (24.6 +/- 4.2 ng leukotriene C4/10(6) MBMMC). The PF HRF did not appear to be a cytokine previously identified in BAL fluid of patients with PF (i.e., platelet derived growth factor or insulin growth factor-1) or a human cytokine able to degranulate human basophils (i.e., IL-1, or granulocyte-macrophage-CSF) as these recombinant human cytokines did not induce MBMMC beta-hex release. Physicochemical characterization of the HRF revealed that it was relatively heat stable, pronase sensitive and on Sephadex G-75 and G-200 column chromatography had an apparent molecular mass of 30 to 50 kDa. The ability of PF BAL to induce beta-hex release from MBMMC was not dependent on IgE as unsensitized or lactic acid treated MBMMC release similar amounts of beta-hex compared to MBMMC sensitized with IgE. Thus, BAL fluid of patients with PF contains an HRF that induces beta-hex release from MBMMC via an IgE-independent mechanism. The presence of the HRF could explain elevated BAL histamine levels in patients with PF.
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PMID:Mast cells and pulmonary fibrosis. Identification of a histamine releasing factor in bronchoalveolar lavage fluid. 169 11

The c-kit proto-oncogene encodes the receptor for a novel hemopoietic cytokine, termed stem cell factor (SCF) or mast cell growth factor (MGF) according to its stimulating spectrum. The human receptor for SCF/MGF is expressed in a subset of normal bone marrow progenitor cells, in leukemic myeloid cells, and in mast cells. In the present study, the effects of recombinant human growth regulators (IL-1 through -9, granulocyte-macrophage/granulocyte/macrophage-CSF, IFN, and TNF) on c-kit proto-oncogene product expression were analyzed by indirect immunofluorescence, by using the anti-SCF/MGFR mAb YB5.B8, and Northern blot analyses, by using a c-kit oligonucleotide probe. Of all cytokines tested, IL-4 was found to down-regulate expression of YB5.B8 Ag in the human mast cell line HMC-1 (maximum inhibition, 51.05 +/- 16.36% mean fluorescence intensity of control; p less than 0.02), as well as in primary leukemic myeloid cells. IL-4 was also found to down-regulate expression of YB5.B8 Ag in normal enriched bone marrow progenitor cells. The effects of IL-4 on expression of YB8.B8 Ag in myeloid/mast cell progenitors was dose and time dependent (maximum effects observed on days 2 and/or 4, by using 50 U/ml of rIL-4) and could be neutralized by using anti-IL-4 mAb. Moreover, IL-4 was found to down-regulate expression of c-kit mRNA in leukemic myeloid cells as well as in HMC-1 cells. Together, these observations identify IL-4 as a regulator of c-kit proto-oncogene product expression in the human system. The effects of IL-4 on human hemopoietic progenitor cells and mast cells may be mediated in part through regulation of SCF/MGFR expression.
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PMID:IL-4 regulates c-kit proto-oncogene product expression in human mast and myeloid progenitor cells. 172 42

The hematopoietic growth factor interleukin (IL)-3 is a potent regulator of blood cell proliferation. It promotes the survival, proliferation, and development of hematopoietic stem cells and committed progenitor cells of the granulocyte-macrophage, erythrocyte, eosinophil, basophil, megakaryocyte, mast cell, and lymphocyte lineages. In addition, IL-3 enhances mature myeloid cell functions such as phagocytosis and activation of basophils and eosinophils, as well as monocyte cytotoxicity. The first phase of clinical trials suggested that IL-3 may augment myelopoiesis in a number of clinical conditions. It may be efficacious for treatment of primary marrow disorders, including myelodysplastic syndromes and aplastic anemia. However, replacement therapy with IL-3 alone is probably not sufficient to obtain maximal stimulation of myelopoiesis. Preclinical and clinical studies published to date suggest that sequential use or combinations of growth factors will be needed to obtain optimal hematopoietic responses.
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PMID:Interleukin-3. Its biology and potential uses in pediatric hematology/oncology. 178 68

Murine interleukin 3 (IL-3) induces a strong, concomitant increase in histamine, interleukin 6 (IL-6), and interleukin 4 (IL-4) synthesis by progenitor-enriched bone marrow cell populations, whereas interleukin 2 (IL-2) or interferon-gamma (IFN-gamma) are undetectable. This phenomenon is observed between 4 and 12 h after exposure to the growth factor and attains maximal cytokine and histamine levels within 24 and 48 h, respectively. None of these mediators is produced by lymphoid populations such as lymph node cells or by granulocytes. Splenocytes secrete only low histamine and IL-6 levels, in accordance with the lower incidence of progenitors in the spleen, whereas total bone marrow cells generate substantial amounts of the three mediators even before enrichment. Histamine, IL-4-, and IL-6-producing cells copurify with immature cells and cannot be separated from each other throughout the sorting procedures used herein. They are concentrated in the low-density layers (buoyant density 1.069-1.086 g/cm3) of a discontinuous Ficoll gradient (less than 4% of the total bone marrow) together with the majority of hematopoietic progenitors (marrow-repopulating ability [MRA] cells, spleen colony-forming units [CFU-S] day-8 and day-12, granulocyte-macrophage colony-forming units [CFU-GM], and mast cell precursors). Their lightscatter characteristics are those of relatively large, granular cells. They do not belong to the most primitive stem cell subset (MRA and part of CFU-S day-12), but to a population with high mitochondrial activity identified by their important rhodamine retention (colony-forming unit cells [CFU-C], blast cells). In addition, we provide evidence that histamine, IL-4, and IL-6 do not depend on each other for their respective expression. Taken together, our data are consistent with the notion that in certain conditions, immature hematopoietic cells are a potent source of histamine and cytokines.
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PMID:Concomitant histamine, interleukin 4, and interleukin 6 production by hematopoietic progenitor subsets in response to interleukin 3. 183 45

The effect of aging process on the hemopoietic system in senescence-accelerated (SAM-P) mice with respect to numbers of hemopoietic progenitor cells was investigated. The numbers of femoral granulocyte-macrophage colony-forming cells (CFU-GM), mast cell progenitors (mast colony-forming units, CFU-Mast), erythroid burst-forming units (BFU-E), and erythroid colony-forming units (CFU-E) in old mice (30-35 weeks old) decreased to 96%, 81%, 83%, and 87% of those of young mice (8-12 weeks old), respectively. The numbers of femoral fibroblast colony-forming cells (CFU-F) in old mice increased to 315% of those of young mice. The numbers of splenic CFU-GM, CFU-Mast, BFU-E, and CFU-E in old mice decreased to 7%, 43%, 25%, and 40% of those of young mice, respectively. In contrast, significant changes in these progenitor cells were not observed in the bone marrow. These findings suggest that the effect of the aging process on hemopoietic tissues in SAM-P mice is predominantly in the spleen.
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PMID:Age-related changes in various hemopoietic progenitor cells in senescence-accelerated (SAM-P) mice. 189 62

The levels of mRNA that encode a number of cytokines have been reported by several laboratories to be increased in mouse mast cells after their IgE-bearing receptors have been cross-linked with Ag. In this study, we have compared the mRNA levels for Fc epsilon RI alpha, three cytokines (IL-6, granulocyte-macrophage CSF, and TNF-alpha), actin and three secretory granule-localized proteins (carboxypeptidase A, proteoglycan peptide core, and a generic serine protease) in mouse bone marrow-derived mast cells (BMMC) before and after IgE-mediated activation and degranulation to determine the kinetics and specificity of mRNA induction. An antigen concentration of approximately 10 ng/ml was optimal for the release of histamine from IgE-sensitized BMMC and for the generation and release of a cytokine that was functionally and immunochemically identical to TNF-alpha. In kinetic experiments, the levels of TNF-alpha, IL-6, and granulocyte-macrophage CSF mRNA increased greater than 23-fold 0.5 to 1 h after activation. As assessed by in situ hybridization, virtually all BMMC contained detectable proteoglycan peptide core mRNA before and after exposure to Ag, but only approximately one-half of the Ag-treated cells in the culture contained IL-6 mRNA 1 h after activation. There was a slight transient increase at 4 h in the level of proteoglycan peptide core mRNA, but no increase in the levels of those highly expressed mRNA that encode actin, Fc epsilon RI alpha, carboxypeptidase A, and serine protease. Thus, despite the remarkable increment in the levels of the transcripts that encode cytokines in BMMC after IgE-mediated, Ag-dependent activation, the levels of those transcripts that encode a plasma membrane-localized recognition receptor and several constituents of the secretory granule remain essentially unchanged. The failure to increase substantially the level of protease and proteoglycan peptide core mRNA in mast cells after the activation/secretion response suggests that regranulation of mast cells is a slow process.
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PMID:Cytokine mRNA are preferentially increased relative to secretory granule protein mRNA in mouse bone marrow-derived mast cells that have undergone IgE-mediated activation and degranulation. 199 42


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