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)

We have identified a late, committed stage in the differentiation of the mast cell progenitor just before granulation. Mast cell committed progenitors (MCCP) are nongranulated cells with a density of 1.060 to 1.070 g/ml which can be harvested from the mesenteric lymph node of mice infected with Nippostrongylus brasiliensis. Mast cell-committed progenitors are able to proliferate and differentiate in the absence of IL-3 or IL-4 when cultured on a monolayer of embryonic skin or 3T3 fibroblasts and can form colonies in methylcellulose supplemented with fibroblast conditioned medium. Fibroblast conditioned medium appears to contain a soluble MCCP proliferation factor that maintains biologic activity when heated to 56 degrees C for 45 min but is destroyed by incubation with either trypsin or chymotrypsin. It can be selectively precipitated with 60 to 70% saturated ammonium sulfate. The factor is not absorbed by immobilized antibodies to nerve growth factor. The MCCP proliferation activity of the factor could not be mimicked by IL-1, IL-2, IL-4, granulocyte-macrophage-CSF, granulocyte-CSF, macrophage-CSF, IFN-alpha/beta, IFN-gamma, nerve growth factor, epidermal growth factor, serum fibronectin, heparin, or a number of glycosaminoglycans. At high salt concentrations, the factor passes through a 50-kDa membrane and can be concentrated above a 5-kDa membrane. MCCP acquire a connective tissue phenotype when cultured on a fibroblast monolayer and a mucosal phenotype when cloned in the presence of conditioned medium from PWM-stimulated spleen cells. When cultured in the absence of IL-3 on a monolayer of embryonic skin or 3T3 fibroblasts, mast cell-committed progenitors produce mast cells which stain with berberine sulfate suggesting a connective tissue phenotype; however, the mast cells that develop when mast cell-committed progenitors are cultured in the presence of IL-3 or conditioned media from PWM-stimulated spleen cells do not stain with berberine sulfate. MCCP intercalate into monolayers of embryonic skin or 3T3 fibroblasts, but T cells are not able to associate with the monolayer and can be completely washed away. Attempts to enrich mast cell-committed progenitors by intercalation and elution from embryonic skin monolayers proved unsuccessful, but some enrichment of mast cell-committed progenitors could be achieved by discontinuous Percoll gradients. Thus, we have identified a way to obtain late-stage, mast cell-committed progenitors in an environment that is virtually uncontaminated with other hematopoietic progenitors.
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PMID:The mast cell-committed progenitor. I. Description of a cell capable of IL-3-independent proliferation and differentiation without contact with fibroblasts. 278 62

A series of permanent IL-3-dependent cell lines have been established from normal BALB/c or C3H bone marrow using alpha-thioglycerol-supplemented culture medium and PWM-stimulated spleen cell-conditioned medium as a source of IL-3. The cell lines and derivatives cloned in agar resembled "mucosal type" mast cells with respect to phenotypic and functional properties. In this report we demonstrate that in vitro growth of these mast cell lines was not only dependent on IL-3 and synergistically enhanced by IL-4, but in addition regulated by alpha-thioglycerol which could be replaced by 2-ME or cysteamine. We show that these thiol-sensitive mast cell lines respond to a mast cell growth enhancing activity (MEA) present in spleen cell-conditioned medium and acting in concert with IL-3. Partially purified MEA was not able to stimulate the growth of IL-3-dependent 32Dcl.23 cells, IL-2-dependent CTLL-2 cells or the mouse T cell line F4/4K.6 (L3T4+) adapted to grow in purified IL-4. Moreover, 11B11 hybridoma-derived anti-IL-4 mAb specifically neutralizing mouse Il-4 were unable to abolish the bioactivity of MEA. PWM, CSF-1, GM-CSF, IL-1, IL-2, IL-5, IL-6, IL-7, IFN-gamma, TGF-alpha, TNF-alpha, NGF, or EPO did not substitute for MEA in our standard proliferation assay.
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PMID:Thiol-sensitive mast cell lines derived from mouse bone marrow respond to a mast cell growth-enhancing activity different from both IL-3 and IL-4. 278 56

PWM-activated spleen cell-conditioned medium (SCCM) and a variety of purified hematopoietic growth factors were tested for their ability to stimulate chemotaxis of mouse connective tissue mast cells (CTMC). Of the agents tested, only IL-3 and SCCM promoted mast cell chemotaxis. Neither IL-2, IL-4, GM-CSF, nor endotoxin had any significant mast cell chemotactic activity. Neutralizing antibodies to mouse IL-3 blocked greater than 90% of the chemotactic activity of SCCM, suggesting that IL-3 is the predominant mast cell chemotactic factor produced by activated spleen cells. Our results demonstrate that mature connective tissue type mast cells are capable of moving toward a gradient of spleen cell-derived IL-3 and suggest that movement of mature mast cells toward lymphokines may influence the accumulation of mast cells at sites of inflammatory or immune reactions.
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PMID:Stimulation of mast cell chemotaxis by interleukin 3. 279 61

We have investigated the role of mast cells as modulators of lymphocyte function because the mast cells are concentrated in the areas of lymphoid storage; they are dependent upon T-cell growth factor for their proliferation; and they appear to be the principle if not sole storage site for histamine. We have tested the influence of mast cells on the proliferation of alloreactive cloned helper T cells, mixed leukocyte reactions, and the suppressive capacity of natural suppressor cells. We used an IL-3-dependent mast cell line that at high numbers (greater than 10(5)) suppressed and at low numbers (10(3) to 6 X 10(4)) augmented the proliferation of TH cells. Addition of histamine to cocultures enhanced the mast cell mediated proliferation of TH cells without directly affecting the helper cells. The action of histamine appeared to be mediated with H1 type receptors on these mast cells. Pretreatment of natural suppressor cells with supernatants from mast cell enhanced their suppressive capability. Here too, histamines enhanced suppression by the NS cell via histamine type 1 receptors on the natural suppressor cells. Our data suggest that mast cells may be a major modulator of the lymphoid cell immune function and demonstrate a role of histamine type 1 receptors in the interaction between mast cells, helper T cells, and natural suppressor cells.
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PMID:Regulatory effects of mast cells on lymphoid cells: the role of histamine type 1 receptors in the interaction between mast cells, helper T cells and natural suppressor cells. 287 38

In this paper, the effect of tritoqualine (TRQ) on the proliferation of interleukin (IL) sensitive cells was investigated. TRQ inhibited the proliferation of FDCp-2 (IL-3 dependent cell line), CTLL-2 (IL-2 dependent cell line) and bone marrow cells (BMC) stimulated by IL, giving an ID50 of about 3 microM equally in the three systems. However, a ten times higher concentration of TRQ was required to inhibit the tumor cell proliferation. TRQ did not affect the unstimulated bone marrow cells. Accordingly, it is suggested that TRQ may show its anti-allergic effect, at least partially, by interfering with the proliferation/differentiation to mast cell and basophils of multi-functional hemato-poietic cells stimulated by IL-3.
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PMID:Effect of tritoqualine on the proliferation of interleukin-3 dependent cell line and sensitive cells. 289 57

Based on homology with the mouse interleukin 4 (IL-4) cDNA that expresses B cell, T cell, and mast cell stimulating activities (Lee, F. et al., (1986) Proc. Natl. Acad. Sci. USA 83, 2061), we have isolated from a Balb/c mouse liver DNA library the mouse chromosomal gene and analyzed its overall structure. The gene occurs as a single copy in the haploid genome and contains four exons and three introns. The exon sequences almost completely match the cloned cDNA sequence. Interestingly, there is a fairly high degree of homology between mouse IL-4 and mouse IL-2 genes extending more than 200 bp upstream of a "TATA" like sequence located 20 bp upstream of the transcription initiation site. These sequences may play an important role in the regulated expression of this gene in concanavalin A or antigen-stimulated T lymphocytes. The supernatant of COS7 cells transfected with plasmid DNA containing the entire gene exhibited both T cell growth factor and mast cell growth factor activities.
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PMID:Structural analysis of the mouse chromosomal gene encoding interleukin 4 which expresses B cell, T cell and mast cell stimulating activities. 302 76

Because previous studies showed low levels of IFN-gamma in rheumatoid arthritis (RA) synovial fluid (SF) and synovial tissue (ST) explant supernatants, we assayed RA SF and ST for IL-2 and IL-3-like activity. Using an IL-2 dependent murine CTLL line, 6 of 14 RA SF caused increased thymidine uptake (greater than three times control). The activity was distinct from IL-2 because it was not blocked by antibody to IL-2-R. In addition, IL-2 was not detected (less than 50 pg/ml) in 16 joint samples using an ELISA. Multi-colony-stimulating factor (CSF) activity was measured using two assays that can detect murine IL-3 (mast cell proliferation, and bone marrow CSF). In the mast cell assay, [3H]TdR uptake was 493 +/- 67 cpm for medium, 2,910 +/- 329 cpm in the presence of RA SF (p less than 0.001), 1,246 +/- 156 cpm in the presence of SF from patients with seronegative spondyloarthropathies (p less than 0.001), and 736 +/- 100 cpm in the presence of osteoarthritis SF (p greater than 0.1). In the CSF assay, four of five RA SF and five of five RA ST induced colony formation from bone marrow nonadherent cells. Macrophage colonies were most common, although mixed colonies and granulocytes were occasionally observed. The multi-CSF activity in RA is not due to IL-3 since human rIL-3 was not active in either murine assay, and IL-3 mRNA was not detected in RA synovium. Sephadex column chromatography of RA SF revealed that the mast cell growth factor (approximately 6 x 10(3) mol wt) and the CSF (approximately 40 and 100 x 10(3) mol wt) are distinct. The colony-stimulating aspect of the "IL-3-like" activity in RA SF is likely due to CSF-1 because it is the appropriate mol wt and because the activity was neutralized by specific anti-CSF-1 antibody. Finally, an RIA detected 1.6-25 ng/ml of CSF-1 in RA SF and ST and CSF-1 mRNA was detected in four of five RA synovial tissue samples tested.
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PMID:Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis. 326 64

Interleukin 4 (IL-4) expresses multiple biologic activities, including B cell, mast cell, and T cell stimulation. We showed that the incubation of resting splenocytes from C57BL/6 mice solely in purified native or recombinant mouse IL-4 results in the generation of lymphokine-activated killer (LAK) activity directed against fresh, syngeneic sarcoma cells. The precursor activated by IL-4 expresses surface asialo-GM1. In addition, IL-4 is capable of amplifying the splenic LAK activity induced by recombinant IL-2. The generation, by IL-4, of killer cells with broad antitumor reactivity raises the possibility of using IL-4 alone or in combination with IL-2 in the immunotherapy of cancer in animal models.
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PMID:Interleukin 4 (B cell stimulatory factor 1) can mediate the induction of lymphokine-activated killer cell activity directed against fresh tumor cells. 349 2

The epidermis has been identified as an important site for the initiation of immunological events. In addition to the macrophage-like Langerhans cells, keratinocytes within the epidermal cells have been shown to act as immunoregulatory cells through the secretion of cytokines such as epidermal cell-derived thymocyte-activating factor (ETAF) and interleukin 3. Epidermal cell-derived interleukin 3 (EC IL-3), like lymphocyte-derived IL-3, induced the proliferation of IL-3-dependent mast cell-like cell lines. Biochemically, EC IL-3 was a heat-stable protein with a molecular weight of approximately 30 kD. Upon chromatofocusing, EC IL-3 exhibited three isoelectric points, at pI 7.8, 7.4, and 7.1. Furthermore, an antiserum against IL-3 neutralized EC IL-3 activity, suggesting that the molecules are closely related and share similar epitopes. ETAF-like macrophage-derived interleukin 1 (IL-1) is a low molecular weight protein with a multiplicity of amplifying effects on immunological and inflammatory reactions. Thus BALB/c mice were immunized with partially purified IL-1, and immune spleen cells were hybridized with plasmocytoma cells. Supernatants of the hybridoma cultures were screened for their capacity to inhibit IL-1-induced thymocyte proliferation. After expansion and cloning, one clone was selected for ascitic antibody production. The monoclonal anti-IL-1 antibody inhibited both the IL-1-dependent thymocyte and the fibroblast proliferation. Furthermore, the antibody blocked murine and human ETAF activity, suggesting that ETAF and IL-1 share antigenically similar domains. Moreover, by using the monoclonal antibody bound to Staphylococcus aureus cells, it was possible to immunoprecipitate IL-1. In contrast, anti-IL-1 antibody did not inhibit IL-2 or IL-3 activity. These findings demonstrate that the production of immunoregulatory cytokines is not confined to cells of the immune system and that keratinocytes through the production of ETAF and EC IL-3 may mediate inflammatory and hypersensitivity reactions. Furthermore, the monoclonal anti-IL-1 antibody may provide a useful tool for the development of new immunoassays to detect IL-1/ETAF and thereby facilitate the investigation of the role of these cytokines during the pathogenesis of inflammatory diseases.
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PMID:Characterization of immunoregulatory cytokines produced by epidermal cells. 389 Jan 50

Bone marrow-derived (colony-stimulating factor [CSF]-dependent) diffuse colonies have been shown to include colonies with cytotoxic activity. Such diffuse colonies were expanded for 6-8 weeks in liquid culture medium in the presence of pokeweed mitogen- or concanavalin A-conditioned spleen cell medium (CM). The morphology of the expanded diffuse colony cells (EDCC) was like that of early myelocytic cells. EDCC lost their cytotoxic capacity when expanded, but the cytotoxicity could be reinduced by pretreatment of the colonies with interferon or phorbol ester. Traditional sources of mouse or human CSF such as lung CM, placenta CM and human mononuclear cell CM did not support proliferation of EDCC, whereas partly purified interleukin-3 (IL-3), lacking CSF and IL-2, was stimulatory for EDCC. Thus, the stimulatory factor for EDCC was not CSF but a factor closely related to IL-3. Monoclonal antibodies against T lymphocytes or macrophages did not bind to EDCC. EDCC did not have Fc receptors, but 10% of the cells were positive for a monoclonal anti-Ia antibody. All EDCC were positive for alpha NAE and NASDCI esterases but negative for acid and alkaline phosphatases and peroxidase reactivity; less than 2% of the cells showed metachromatic staining with toluidine. Ultrastructurally, EDCC showed various degrees of cell differentiation but absence of specific cytoplasmatic characteristics such as neutrophilic, eosinophilic, basophilic and mast cell granules. Current work aims to define factors and conditions necessary for the induction of differentiation in these immature monomyelocytic cells.
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PMID:Expanded progeny cells of diffuse cytotoxic bone marrow-derived colonies. 618 13


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