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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine mast cell development is regulated by a number of T cell- and fibroblast-derived growth factors, of which IL-3 and stem cell factor (SCF) appear to be the most important. To determine the relative effects of these two growth factors on different stages of developing mast cells, we isolated highly purified populations of c-kit+ mast cells and their progenitors and examined their ability to respond to SCF and/or IL-3. We show that purified c-kit+ cells isolated from bone marrow, mesenteric lymph nodes of Nippostrongylus brasiliensis-infected mice, and the peritoneal cavity do not form mast cell colonies in response to SCF as a single agent. Although unpurified populations of lymph nodes of Nippostrongylus brasiliensis-infected mice or peritoneal cells were able to form mast cell colonies in response to SCF alone, this probably reflects paracrine factors produced by accessory cells. IL-3 alone did not promote mast cell colony formation from either population. Within bone marrow, we detected both multipotential and unipotential mast cell progenitors. Interestingly, IL-3 alone promoted only the development of multipotential progenitors, while SCF plus IL-3 promoted both multipotential and unipotential mast cell progenitors. Together, these results indicate that the developmental/proliferative effects observed with a particular mast cell population is determined in part by the stage of maturation of mast cells at the time they are exposed to SCF and IL-3, and suggest that SCF primarily influences mast cell development only in the context of other cytokines.
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PMID:Differential responsiveness of purified mouse c-kit+ mast cells and their progenitors to IL-3 and stem cell factor. 756 Nov 12

The effects of recombinant canine stem cell factor (rcSCF) on hematopoiesis were studied in normal dogs and in dogs given otherwise lethal total body irradiation (TBI) without marrow transplant. Results were compared with previous and concurrent data with recombinant granulocyte colony-stimulating factor (rG-CSF). Four normal dogs received 200 micrograms rcSCF per kilogram body weight daily either by continuous intravenous infusion for 28 days (n = 2) or by subcutaneous (SC) injection in two divided doses for 20 days (n = 2). All dogs showed at least a twofold increase in peripheral blood neutrophil counts starting approximately 7 days after the initiation of treatment. Hematocrit level and monocyte, lymphocyte, eosinophil, reticulocyte, and platelet counts were not elevated. Marrow sections after rcSCF treatment showed panhyperplasia. The only toxicity was facial edema during the first few days of rcSCF administration, presumably caused by mast cell stimulation. Ten dogs were given 400 cGy TBI at 10 cGy/min from two opposing 60Co sources. They were given no marrow infusion and received 200 micrograms/kg/d rcSCF SC in two divided doses for 21 days starting within 2 hours of TBI. Five of the 10 dogs showed complete and sustained hematopoietic recovery and survived as compared with 1 of 28 control dogs not receiving growth factor (P < .005). RcSCF treatment allowed for hematopoietic recovery in two of seven dogs administered 500 cGy of TBI but in none of five dogs given 600 cGy of TBI. Results with rcSCF are similar to those obtained with rG-CSF. The rate of neutrophil recovery in rcSCF-treated dogs after 400 cGy TBI was not different from that of rG-CSF-treated dogs (P = .65), but the rate of platelet recovery was faster (P = .06) in the rcSCF-treated animals. Combined treatment with rcSCF and rcG-CSF after 500 cGy TBI did not result in strongly improved survival as compared with results obtained with either factor alone.
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PMID:Effects of recombinant canine stem cell factor, a c-kit ligand, and recombinant granulocyte colony-stimulating factor on hematopoietic recovery after otherwise lethal total body irradiation. 767 65

We examined whether three cytokines that promote mouse mast cell development, the c-kit ligand stem cell factor (SCF), IL-3, or IL-4, also can directly stimulate or modulate mouse peritoneal mast cell (PMC) mediator release. Challenge of purified PMC with rat rSCF164 at 20 to 100 ng/ml for 30 min induced a modest release of serotonin (5-HT), whereas IL-3 or IL-4 did not directly stimulate 5-HT release. Experiments in which PMC were exposed to each cytokine for 15 min, and then to DNP-HSA Ag or anti-IgE antibody for a further 15 min, showed that SCF, but not IL-3 or IL-4, had an additive effect on the 5-HT release induced by either of the IgE cross-linking agents. In longer term experiments, SCF (0.16 to 500 ng/ml), IL-3 (2.5 to 100 ng/ml), or IL-4 (0.06 to 2.5 ng/ml) was added to peritoneal cell cultures for 48 h, during which the cells were passively sensitized with IgE anti-DNP antibody. Incubation of either unfractionated or highly purified PMC preparations with each of the three cytokines resulted in a concentration-related increase in 5-HT release upon subsequent challenge of the cells with DNP-HSA Ag. However, after pretreatment of peritoneal cells for 48 h with each cytokine, only IL-4 (10 ng/ml) enhanced release of 5-HT induced by calcium ionophore A23187 (0.25 microM); IL-3 (100 ng/ml) had no effect, whereas SCF (100 ng/ml) significantly inhibited ionophore-induced release. Although IL-3 or SCF up-regulate responsiveness to IgE-dependent stimuli, we detected no effect of these cytokines on the binding of [125I]IgE to PMC. This suggests that the enhancing effects of SCF or IL-3 on IgE-dependent 5-HT release did not simply reflect changes in the amount of IgE bound to the cells. In conclusion, we found that SCF, IL-3, or IL-4 each exerted a different spectrum of stimulatory, costimulatory, or regulatory effects on the secretory function of mouse PMC.
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PMID:Regulation of mouse peritoneal mast cell secretory function by stem cell factor, IL-3 or IL-4. 767 75

Mast cell development in mice is critically regulated by stem cell factor (SCF), the term used here to designate a product of fibroblasts and other cell types that is a ligand for the tyrosine kinase receptor protein encoded by the proto-oncogene c-kit. However, the factors which regulate the size of mast cell populations in primates are poorly understood. Here we report that the subcutaneous administration of recombinant human SCF (rhSCF) to baboons (Papio cynocephalus) or cynomolgus monkeys (Macaca fascicularis) produced a striking expansion of mast cell populations in many anatomical sites, with numbers of mast cells in some organs of rhSCF-treated monkeys exceeding the corresponding values in control monkeys by more than 100-fold. Animals treated with rhSCF did not exhibit clinical evidence of mast cell activation, and discontinuation of treatment with rhSCF resulted in a rapid decline of mast cell numbers nearly to baseline levels. These findings are the first to demonstrate that a specific cytokine can regulate mast cell development in primates in vivo. They also provide the first evidence, in any mammalian species, to indicate that the cytokine-dependent expansion of tissue mast cell populations can be reversed when administration of the cytokine is discontinued.
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PMID:Reversible expansion of primate mast cell populations in vivo by stem cell factor. 767

Stem cell factor (SCF) is encoded at the Sl locus of the mouse and is the ligand for the c-kit receptor. Recombinant rat SCF164 (rrSCF164) induces proliferation and promotes maturation of mouse mast cells in vitro and in vivo and can also induce c-kit receptor-dependent mouse mast cell degranulation. We now report that in both quiescent and non-quiescent mouse bone marrow-derived cultured mast cells (BMCMC) rrSCF164 induces increased mRNA levels for the "early response genes" c-fos, c-jun and junB but has only slight effects on the expression of junD. Recombinant mouse interleukin-3 (IL-3) also promotes proliferation of both quiescent and non-quiescent BMCMC. However, IL-3 induces increased expression of c-fos and junB only in quiescent BMCMC. Cross-linking of Fc epsilon receptor type I (Fc epsilon RI) on BMCMC by IgE and specific antigen induces a pattern of early gene expression very similar to that induced by rrSCF164. However, BMCMC stimulated through the Fc epsilon RI did not proliferate and, in comparison to control BMCMC, exhibited significantly decreased proliferation in response to rrSCF164 or IL-3. These results indicate that stimulation of BMCMC proliferation by IL-3 or rrSCF164 induces distinct patterns of early response gene expression and suggest that the proliferative effects of these growth factors may be mediated through distinct signal transduction pathways. Our data also point to previously unappreciated similarities between the effects of signaling through the c-kit receptor or the Fc epsilon RI on mast cell expression of fos and jun genes.
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PMID:Distinct patterns of early response gene expression and proliferation in mouse mast cells stimulated by stem cell factor, interleukin-3, or IgE and antigen. 768

The retinoic acid-stimulated mouse-transformed epidermal cell line Pam 212 generated soluble mediators (RA-Pam sup) which showed mast cell-proliferating activity and induced mast cell-like colonies from bone marrow cells. Both mucosal-type and connective tissue-type mast cells were demonstrated on histochemical analysis. The 3T3 fibroblast cell line or human trichilemmomal cell line (TL1) also generated similar molecules on retinoic acid stimulation. Anti-stem cell factor antibody presented a rather more potent inhibitory activity on RA-Pam sup-dependent mast cell colony formation than did anti-IL3 and -IL4 antibodies. RA-Pam sup only induced mast cell colonies in semisolid culture and failed to promote mast cell growth in a suspension culture. In addition, mast cell colonies showed close contact with fibroblast-like cells on the methylcellulose plate, but this finding was not observed in culture without RA-Pam sup.
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PMID:Induction and characterization of mast cell colonies by culture supernatant of retinoic acid-treated mouse keratinocytes. 768 25

The recently identified ligand for c-kit, a protooncogene encoded by the W locus in mice, is a member of the tyrosine kinase receptor family with growth factor activity for mouse mast cells. Mature human mast cells regularly develop from agranular precursors in cord blood in long-term cocultures of cord blood and murine fibroblasts. Since the c-kit ligand is a product of murine fibroblasts, we examined the growth effect of recombinant human c-kit ligand (stem cell factor), of recombinant murine c-kit ligand (mast cell growth factor), and of a partially purified fraction derived from mouse fibroblast culture supernatant on the mast cell lineage of humans by electron microscopy in 8-week cultures of cord blood cells. We found that immature mast cells which developed in cultures containing the recombinant ligand for c-kit of human or murine origin as well as the naturally occurring c-kit ligand in 3T3 fibroblast supernatants were identical. Thus, each of these sources of the c-kit ligand exerted identical effects on the ontogeny of human mast cells as they develop from their agranular precursors in cord blood. Full maturity of factor-supported mast cells did not occur.
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PMID:Human and murine recombinant c-kit ligands support the development of human mast cells from umbilical cord blood cells: ultrastructural identification. 768 96

Human foetal liver cells are an enriched source of mast cell progenitors that complete their differentiation and mature in response to stem cell factor, the ligand for Kit, in liquid culture. These mast cells are Kit+, metachromatic with toluidine blue+, tryptase+, histamine+ and show ultrastructure features of mast cells. Using a panel of monoclonal antibodies (mAb) against different cell-surface antigens (33 mAb were used), the cell-surface phenotype of human stem cell factor-dependent foetal liver-derived mast cells was examined by flow cytometry. Consistent with previous reports on tissue-derived mast cells, those derived from foetal liver in vitro expressed HLA class I, CD9, CD29, CD33, CD43, CD45 and Kit. Unlike mast cells dispersed from tissue, a high expression of CD13 was found. Also, these in vitro-derived mast cells express little, if any, high-affinity IgE receptor. However, small amounts of mRNA for the alpha-chain in foetal liver-derived mast cells compared to KU812 cells (a human basophil-like cell line) could be detected by Northern blotting. Full expression of Fc epsilon RI may require additional growth factor(s).
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PMID:Phenotypic characterization of stem cell factor-dependent human foetal liver-derived mast cells. 768 44

It is well established that mast cell proliferation and maturation are regulated by two principle cytokines, IL-3 and the c-kit ligand stem cell factor (SCF). Little is known, however, how these two processes are negatively regulated and thus, how mast cell number is controlled in normal or pathologic processes. In this study we hypothesized that IL-3-dependent mast cells would undergo programmed cell death (apoptosis) on removal of IL-3 as was shown with other growth factor-dependent hemopoietic cells. Apoptotic changes were analyzed using light microscopy, fluorescent staining with acridine orange, flow cytometric analysis, and DNA electrophoresis. We could demonstrate that elimination of IL-3 from either primary bone marrow-derived cultured mast cell cultures (BMCMC) or from the growth factor-dependent mast cell line MCP5 resulted in the characteristic changes of apoptosis including condensed chromatin, fragmented nuclei, cellular vacuolization, typical pattern of propidium iodide or Hoechst 33342 uptake by flow cytometry, and the characteristic 200 bp "ladder" pattern of DNA cleavage. These events were prevented by SCF, an action that was in part mediated by tyrosine kinases, in that the tyrosine kinase inhibitor herbimycin inhibited the action of SCF in preventing apoptosis in IL-3-deprived cells. By using anti c-kit mAb and IL-3-dependent BMCMC obtained from W/Wv mice homozygous for mutation at the w locus that encodes the c-kit receptor, we could also show that SCF exerted its effect via c-kit. Neither dexamethasone nor cyclosporin A inhibited the "rescue" effect of SCF, suggesting that "rescue" was mediated by SCF and not through the induction of other cytokines. Thus, IL-3-dependent mast cells undergo apoptosis on removal of IL-3, an event that is prevented by the addition of SCF through its ligand c-kit, thus demonstrating how these principle mast cell growth factors may act in concert to regulate mast cell number under physiologic conditions.
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PMID:IL-3-dependent murine mast cells undergo apoptosis on removal of IL-3. Prevention of apoptosis by c-kit ligand. 769 Aug 14

Stem cell factor (SCF) is known to alter the proteoglycans, proteases, and cytokines synthesized by mast cells and to activate basophils. To determine whether SCF could also effect the ultrastructural characteristics of basophils and mast cells, we examined the ultrastructure of these Fc epsilon RI+ cells over 42 days in IL-3-dependent murine bone marrow-derived cell cultures in the presence or absence of SCF. Initial experiments revealed that the addition of SCF to IL-3-dependent cells enhanced their proliferative rate without influencing the percentage of Fc epsilon RI+ or metachromatic cells. We next isolated the Fc epsilon RI+ cells using flow cytometry. Light microscopy of these cells revealed mixed cultures of both immature and mature mast cells and basophils with mature mast cells predominating by 3 wk. One hundred to 150 Fc epsilon RI+ cells were then photographed by electron microscopy at 3, 10, 21, and in some cases, 42 days of culture, and the ultrastructure of each cells was evaluated by morphometry. Each cell was scored as a mast cell or basophil using standard criteria. Analysis of this data revealed that SCF in the presence of IL-3 promoted the development of mast cells, although a significant number of basophils were noted at day 21 but were absent by day 42. When bone marrow cells cultured in IL-3 + SCF were compared with cells cultured in IL-3 alone, a significant decrease in cell and nuclear size and granule number and size was noted in both mast cells and basophils cultured in IL-3 + SCF, and basophils and mast cells under these conditions most resemble their in vivo counterparts. Thus, SCF in the presence of IL-3 increases the ratio of mast cells to basophils and alters the ultrastructural characteristics of mast cells and basophils toward a more mature phenotype.
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PMID:The effects of stem cell factor on the ultrastructure of Fc epsilon RI+ cells developing in IL-3-dependent murine bone marrow-derived cell cultures. 769 60


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