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)

The histamine-producing cell-stimulating factor (HCSF) was first described as a lymphokine which is produced during secondary mixed leukocyte culture and which induces increased histamine synthesis by murine hematopoietic cells. It has been shown that it is different from interleukin 3 (IL 3), despite the fact that pure IL 3 expresses HCSF activity. Our results provide evidence that this factor (constitutively produced by the P388 D1 cell line) is identical with granulocyte-macrophage colony-stimulating factor (GM-CSF) i.e.: (a) physiochemical properties of HCSF and GM-CSF, such as molecular weight, isoelectric charge, hydrophobicity and behavior during affinity chromatography, are indistinguishable and both activities coelute during all biochemical purification procedures; (b) increased bone marrow cell histamine synthesis induced by P388 D1-derived HCSF is inhibited by anti-GM-CSF antiserum; (c) the GM-CSF cDNA probe hybridizes with a poly(A)+RNA from P388 D1 cells while no hybridizing signal was obtained with poly(A)+RNA from WEHI-3 and from P815 cells. On the other hand, the IL 3 cDNA probe hybridizes with a 1.0-kb poly(A)+RNA from WEHI-3 but not with those from P388 D1 and P815. Moreover, well known sources of GM-CSF, such as lung conditioned medium and semi-purified GM-CSF from phytohemagglutinin-induced supernatant of the murine T lymphoma LBRM-33-5 A4 (preparation devoid of IL 3), as well as recombinant murine GM-CSF, induce increased histamine synthesis by hematopoietic cells. All these results demonstrate that, in our culture conditions, the P388 D1 cell line spontaneously produces GM-CSF which is responsible for the P388 D1-induced HCS activity. Consequently, the latter is a property shared by the two distinct hematopoietic growth factors acting on the less committed cells, i.e. IL 3 and GM-CSF, whereas M-CSF or G-CSF are unable to induce histamine production. Interestingly, IL-4 which is known to support established mast cell line proliferation cannot induce HCS activity. In addition, none of the other cytokines tested, such as IL 1, IL 2, interferons or tumor necrosis factor can express HCS activity. This expression seems to be a specific property of IL 3 and GM-CSF.
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PMID:Histamine-producing cell-stimulating activity. A biological activity shared by interleukin 3 and granulocyte-macrophage colony-stimulating factor. 288 59

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

We have previously reported that the population of mesenteric lymph node cells from normal BALB/c mice infected 14 days with the rodent nematode Nippostrongylus brasiliensis (Nb-MLN) contains a nongranulated mast cell-committed progenitor (MCCP) which does not require IL-3 for proliferation and differentiation if either a fibroblast monolayer or soluble factors produced by monolayers of 3T3 fibroblasts or embryonic skin are present in the culture. When Nb-MLN were cloned in a methylcellulose culture system using fibroblast conditioned medium as the only source of growth factors, numerous colonies of pure mast cells developed. We wished to determine whether the mast cell deficiency of W/Wv or S1/S1d mice could be explained by the failure of these mice to make either the MCCP or the factor to support proliferation and differentiation of the MCCP. We found that Nb-MLN from W/Wv mice were only able to produce mast cell colonies in response to a source of IL-3 such as conditioned medium from pokeweed mitogen-stimulated spleen cells (CM), and cultures given fibroblast conditioned medium as the only source of growth factors did not produce mast cell colonies. In contrast, Nb-MLN from mast cell deficient S1/S1d mice developed many mast cell colonies in methylcellulose cultures supplemented with either fibroblast conditioned medium or conditioned medium from PWM-stimulated spleen cells. These data suggest that S1/S1d mice but not W/Wv mice produce the mast cell progenitor that responds to fibroblast conditioned medium. To determine if mast cell deficient mice make the fibroblast derived factors that support development of the MCCP, monolayers were prepared from skin connective tissues of S1/S1d and W/Wv mice and Nb-MLN from normal BALB/c mice were cloned in the presence of conditioned medium from these monolayers. Fibroblast conditioned medium from monolayers prepared from W/Wv but not S1/S1d mice supported development of numerous mast cell colonies. Taken together, these data demonstrate that W/Wv mice are incapable of producing normal MCCP whereas S1/S1d fibroblasts fail to produce the appropriate factor to support the MCCP. In accordance with these data, a candidate for the gene product of each of these mutant alleles is discussed.
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PMID:The mast cell-committed progenitor. II. W/Wv mice do not make mast cell-committed progenitors and S1/S1d fibroblasts do not support development of normal mast cell-committed progenitors. 292 39

A murine interleukin 3 (IL 3)-dependent basophilic mast cell line, PT-18 (A17), and a rat basophilic leukemic cell line, RBL-2H3, were shown to be capable of selective natural cytotoxic (NC) but not natural killer (NK) cell activity. The basophilic cell types could also be augmented in their NC activity by bridging of their surface IgE receptors. IgE-mediated triggering of the basophilic cells was accomplished by coating the cells with IgE and exposing the IgE-bound cells to specific antigen or to anti-IgE monoclonal antibody. Another method of triggering was by direct binding of basophilic cells to anti-IgE receptor monoclonal antibody. Basophilic cells, triggered by these methods, not only displayed increased NC activity but also released a soluble factor capable of selectively lysing NC tumor targets, WEHI-164, but not three of the NK-sensitive targets, YAC-1, RLM1, and RBL-5. Normal C3H/HeJ mouse embryonic fibroblasts were also not lysed. Dose response and time course of the cytotoxic factor release from triggered RBL-2H3 cells were similar to those of tritiated serotonin release. As with serotonin or histamine release, the NC-specific cytotoxic factor (NCCF) was not released in the absence of extracellular calcium. Therefore, NCCF appears to be released along with other mediators during the triggering of basophilic cells by bridging of IgE receptors. The m.w. of the native form of this factor, determined by a gel filtration method, was about 43,000.
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PMID:Natural cytotoxic (NC) cell activity in basophilic cells: release of NC-specific cytotoxic factor by IgE receptor triggering. 294 Feb 98

We previously described the interleukin 3 (IL-3)-dependent cell line, M1-A5, which has both natural cytotoxic (NC) and suppressor cell activities, the latter of which is mediated, in part, by the release of two cytokines which activate suppressor cells from unprimed lymphoid precursor cells. In this study we have compared the M1-A5 cell line with four other IL-3-dependent cell lines to determine whether these dual activities are universally associated with IL-3 dependence and to test the hypothesis that there is a direct relationship between the cytotoxic and the suppressive activities. The cell lines tested were a bone marrow derived Dexter culture derived line (FDC-P1), two Moloney leukemia virus induced leukemias (DA-1 and DA-3), and a mast cell line (PT18(A17]. All lines were dependent on IL-3 for survival but FDC-P1, DA-1, and DA-3 showed varying degrees of short-term proliferation in granulocyte-macrophage colony stimulating factor (GM-CSF). The cell lines all expressed asialo GM1 and Ly-5 surface markers but differed with respect to other markers. DA-1 expressed MAC-1, FDC-P1 and DA-3 expressed Thy-1, and PT18(A17) expressed receptors for the Fc portion of IgE. The cell lines varied greatly in their cytotoxic activity against WEHI-164. FDC-P1, DA-1, and PT18(A17) had low NC activity. DA-3 had consistently high activity, greater than that seen with M1-A5 cells. However, none of the cell lines secreted constitutively a suppressor cell inducing factor (SIF). In addition, it was demonstrated that recombinant murine TNF did not activate suppressor cells capable of inhibiting antibody synthesis and that anti-TNF did not block SIF activity, thus suggesting that TNF contamination of the M1-A5 derived SIF preparation is not responsible for the induction of suppressor cells. We conclude that suppressor cell inducing factors are not universally secreted by IL-3-dependent cell lines, that there is no correlation between NC and SIF activity, and that the dual activities of M1-A5 cells are not mediated by TNF.
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PMID:Secretion of a suppressor cell inducing factor by an interleukin 3-dependent cell line with natural cytotoxic activity. III. Comparison with other interleukin 3-dependent cell lines. 297 53

The functional and biochemical characterization of rat bone marrow derived mast cells (RBMMC) confirms both species-related differences between rat and mouse bone marrow-derived mast cells (MBMMC) as well as mast cell heterogeneity in a single species. Such RBMMC have the staining characteristics of mucosal mast cells and contain the mucosal mast cell protease. The RBMMC release the preformed granule mediator beta-hexosaminidase both in response to immunologic stimulation with 200 ng Ag (net release 15.8 +/- 3.8%) and in response to 1 microM calcium ionophore A23187 (net release 21.8 +/- 6.8%). However, compound 48/80, substance P, and somatostatin did not induce mast cell degranulation. In experiments with optimal beta-hexosaminidase release, the RBMMC generated similar quantities of the newly formed arachidonic acid metabolites leukotriene C4 and PGD2 when stimulated with either Ag or calcium ionophore A23187. The RBMMC incorporate [35S]sulfate into proteoglycans consisting of 90% chondroitin sulfates and 10% heparin. The chondroitin sulfates were comprised of chondroitin 4 sulfate and chondroitin sulfate diB sulfated disaccharides in a ratio of 4/1. Although we show that RBMMC and MBMMC share a low histamine content, functional IgE receptors and unresponsiveness to cromolyn and selective secretagogues (compound 48/80, substance P, and somatostatin), we also provide evidence that RBMMC differ from MBMMC in their profile of newly generated mediators, preformed granule proteoglycan, and lack of proliferative response to mouse IL-3.
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PMID:Functional and biochemical characterization of rat bone marrow derived mast cells. 297 57

Colony-stimulating factors (CSFs) produced by two simian virus 40(SV40) transformed macrophage cell lines (BAM1 and BAM3), and three hybrids (HM3-11, HM3-12, and HM3-14) derived from fusion between BAM3 and a Chinese hamster cell line (hs222-16) were examined. HM3-11 and HM3-14 produce two molecular species of CSF, which are not found in the conditioned media from cultures of BAM1 and BAM3 or lipopolysaccharide (LPS), phorbolmyristate-acetate (PMA), and zymosan-stimulated BAM3. HM3-12, which is classified into another group in terms of CSF secretion, does not produce these two CSFs. On the basis of various criteria, one of these CSF species (peak 1-CSF) was characterized as a macrophage-colony-stimulating factor (M-CSF). The other CSF (peak 2-CSF) induced a group of bone marrow cells in granulocytes and macrophages as well as growth of a mast cell line, IC2. This CSF has an apparent molecular weight of 18,000, estimated by SDS-polyacrylamide gel electrophoresis. Unlike interleukin 3 (IL3) from WEHI-3 cells, the growth factor activity of peak 2-CSF binds to DEAE-Sephacel. Thus, peak 2-CSF is similar to a granulocyte-macrophage colony-stimulating factor (GM-CSF) rather than to IL3. The anti L cell CSF serum does not inhibit the CSF activity in Chinese hamster fibroblast conditioned medium, and the IC2 cells do not respond to Chinese hamster lung conditioned medium (CHLCM), suggesting that peak 1- and peak 2-CSF are of mouse origin.
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PMID:Properties of colony-stimulating factors produced by macrophage cell lines and hybrid cells. 302 9

When spleen cells of 5-fluorouracil (5-FU)-treated mice were cultured in the presence of interleukin 3 (IL-3), most colonies revealed IL-3 concentration-dependent colony formation except for mast cell colonies and blast cell colonies. While most colonies were smaller in lower concentrations of IL-3, the size of the blast cell colonies were similar between high and low IL-3 groups. These data suggested that blast cell colony development requires less IL-3 than the development of multilineage colonies from blast cell colonies. This notion was supported by experiments in which IL-3 was added twice to cultures of spleen cells of 5-FU-treated mice. When low concentrations of IL-3 were added on day 7, there was a reduction in the number of multilineage colonies formed without an effect on the number of blast cell colonies. Using this information, we developed a culture system that favors blast cell colony formation by cells of normal mice. When low (20 U/ml) concentrations of IL-3 were added to cultures of spleen cells of normal mice on day 7 of incubation in media containing 2-5% fetal calf serum, blast cell colonies were the predominant colony type. The blast cell colonies revealed high but variable secondary replating efficiencies. These data suggest that multipotential progenitors may become less sensitive to IL-3 as they differentiate in culture.
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PMID:Declining sensitivity to interleukin 3 of murine multipotential hemopoietic progenitors during their development. Application to a culture system that favors blast cell colony formation. 308 77

A cDNA sequence coding for a unique mouse interleukin that expresses B-cell-, T-cell, and mast-cell-stimulating activities has been isolated from a mouse helper T-cell cDNA library. The library, constructed in the pcD expression vector, was screened by transfecting COS monkey cells with DNA pools to express the products encoded by full-length cDNA inserts. By assaying the transfected cell supernatants, we identified clones encoding a factor that stimulates T-cell and mast cell lines. This factor also induces Ia expression on resting B cells and enhances IgG1 and IgE production by B cells, two properties of B-cell-stimulatory factor 1. The DNA sequence codes for a polypeptide of 140 amino acid residues including a putative signal peptide. These results demonstrate that a single cDNA clone distinct from interleukin 2 and interleukin 3 encodes a polypeptide with multiple biological activities.
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PMID:Isolation and characterization of a mouse interleukin cDNA clone that expresses B-cell stimulatory factor 1 activities and T-cell- and mast-cell-stimulating activities. 308 12

Rats infected with the helminth Nippostrongylus brasiliensis were injected i.p. with 2 mCi of [35S] sulfate on days 13, 15, 17, and 19 after infection. The intestines were removed from animals on day 20 or 21 after infection, the intestinal cells were obtained by collagenase treatment and mechanical dispersion of the tissue, and the 35S-labeled mucosal mast cells (MMC) were enriched to 60 to 65% purity by Percoll centrifugation. The cell-associated 35S-labeled proteoglycans were extracted from the MMC-enriched cell preparation by the addition of detergent and 4 M guanidine HCl and were partially purified by density gradient centrifugation. The isolated proteoglycans were of approximately 150,000 m.w., were resistant to pronase degradation, and contained highly sulfated chondroitin sulfate side chains. Analysis by high-performance liquid chromatography of chondroitinase ABC-treated 35S-labeled proteoglycans from these rat MMC revealed that the chondroitin sulfate chains consisted predominantly of disaccharides with the disulfated di-B structure (IdUA-2SO4----GalNAc-4SO4) and disaccharides with the monosulfated A structure (G1cUA----GalNAc-4SO4). The ratio of disaccharides of the di-B to A structure ranged from 0.4 to 1.6 in three experiments. Small amounts of chondroitin sulfate E disaccharides (GlcUA----GalNAc-4,6-diSO4) were also detected in the chondroitinase ABC digests of the purified rat MMC proteoglycans, but no nitrous acid-susceptible heparin/heparan sulfate glycosaminoglycans were detected. The presence in normal mammalian cells of chondroitin sulfate proteoglycans that contain such a high percentage of the unusual disulfated di-B disaccharide has not been previously reported. The rat intestinal MMC proteoglycans are the first chondroitin sulfate proteoglycans that have been isolated from an enriched population of normal mast cells. They are homologous to the chondroitin sulfate-rich proteoglycans of the transformed rat basophilic leukemia-1 cell and the cultured interleukin 3-dependent mouse bone marrow-derived mast cell, in that these chondroitin sulfate proteoglycans as well as rat serosal mast cell heparin proteoglycans are all highly sulfated, protease-resistant proteoglycans.
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PMID:Intestinal mucosal mast cells from rats infected with Nippostrongylus brasiliensis contain protease-resistant chondroitin sulfate di-B proteoglycans. 308 52


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