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)

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

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

To obtain further information regarding the role of cytokines during mast cell differentiation, we have investigated changes of cytokine secretion in mast cells developing from the human peripheral blood monocytic cell fraction during culture with fibroblast-derived conditioned media. The influence of stem cell factor and an antibody to the respective receptor in our culture system was studied as well. Interleukin (IL)-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor (TNF)alpha were spontaneously secreted by cultured cells at day 1 and decreased markedly by day 14. Similar changes occurred also during culture with stem cell factor and were partially abrogated by an anti-receptor antibody. IL-8 was secreted at a high level throughout the culture, whereas no spontaneous secretion of IL-2, IL-3, IL-4, and IL-7 was measured at all. Upon stimulation with phorbol myristate acetate and A23187, cultured cells showed substantially more release of IL-3 and TNF-alpha after 14 d of culture, compared to peripheral blood monocytic cells. Preformed TNF-alpha was found in one of three monocytic cell preparations from peripheral blood, but not in monocytic cell-derived mast cells. During mast cell differentiation, cytokines from monocytic cells are therefore downregulated while the cells assume a pattern typically found in mast cells.
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PMID:Comparative cytokine release from human monocytes, monocyte-derived immature mast cells, and a human mast cell line (HMC-1). 752 30

FK506 and cyclosporin A (CsA) are immunosuppressive agents that inhibit IL-2 production by activated T cells, but only CsA inhibits IgE activation-induced cytokine transcripts in mouse IL-3-dependent, bone marrow-derived mast cells (BMMC). We previously associated the resistance of BMMC to FK506 with a deficiency in the expression of FK506 binding protein (FKBP) 12, a molecule that forms a complex with FK506 capable of inhibiting calcineurin phosphatase activity in vitro. In this report, we establish that FKBP12 mediates FK506 inhibition of both calcineurin phosphatase activity and IgE activation-induced cytokine transcripts in a Kirsten murine sarcoma virus-immortalized mast cell line that is FKBP12 deficient. Overexpression of FKBP12 by transfection enhanced the ability of FK506 to inhibit calcineurin phosphatase activity (IC50 = 2 nM), compared with cells transfected with the expression vector alone (IC50 > 30 nM). The IC50 value for FK506 inhibition of IgE activation-induced transcripts for TNF-alpha decreased from 40 nM in vector control cells to 10 nM in FKBP12 transfectants. Similarly, the IC50 value for inhibition of IL-6 transcripts decreased from > 1000 nM in vector control cells to 35 nM in FKBP12 transfectants. In contrast, activation-elicited release of the secretory granule mediator beta-hexosaminidase was only partially inhibited by FK506 at 1000 nM, regardless of the levels of FKBP12 expressed by the cells. Thus, FKBP12 is the dominant cytosolic protein that mediates FK506 inhibition of TNF-alpha and IL-6 transcripts.
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PMID:The complex of FK506-binding protein 12 and FK506 inhibits calcineurin phosphatase activity and IgE activation-induced cytokine transcripts, but not exocytosis, in mouse mast cells. 753 Jul 43

Mouse-transformed epidermal cell line (Pam 212) generated the soluble mediators for promoting the growth of a mast cell line (MC9) in the presence of retinoic acid at a concentration of 10(-6)-10(-7) M. The effective molecule of MC9 cell growth promoting factor (MC9-GF) was non-dialyzable and eluted between the molecular weight of 45 K and 68 K on a TSK 2000 G column. Chromatofocusing analysis revealed that this factor had a pI range between 7.0 and 7.5. Anti-c-kit ligand antibody abrogated MC9-GF activity and RT-PCR analysis demonstrated that retinoic acid upregulates c-kit ligand mRNA expression by Pam cells. Several recombinant cytokines including IL1-alpha, IL-1 beta, IL-2, IL-3 or IL-4 did not promote MC9 cell growth at a concentration of 100 U/ml. The presence of anti-IL-1 alpha, -IL-1 beta, -IL-2, -IL-3 or -IL-4 antibodies did not abrogate the MC9-GF activity except for anti-c-kit ligand antibody.
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PMID:Retinoic acid upregulates c-kit ligand production by murine keratinocyte in vitro and increases cutaneous mast cell in vivo. 753 79


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