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 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

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

A 57-year-old female patient, admitted for an acute abdominal syndrome, was found to have an extensive proliferation of mast cells both in the peripheral blood and the bone marrow. Cytochemical studies confirmed the mast cell characteristics of the pathological cell population, while the immunophenotype strongly suggested a bone marrow origin of this malignancy. The course of the disease was not affected by antiproliferative treatment and the patient, after progressive general deterioration, died of intractable haemorrhage. On both clinical and haematological criteria it seems possible to distinguish this rare case of primary mast leukaemia from the more common form of tissue mastocytosis with secondary leukaemia.
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PMID:Mast cell leukaemia: evidence for bone marrow origin of the pathological clone. 309 68

A 29-yr old woman developed urticaria pigmentosa which subsequently progressed through systemic mastocytosis to Philadelphia chromosome negative (Ph neg) chronic myelogenous leukemia (CML) with t(8;17). Further cytogenetic evolution occurred at the time of transformation to the aggressive phase of the disease. Unlike Ph-positive CML, chromosome number 9 was not involved, nor was the breakpoint cluster region located at band 22q11. This clearly separates this case from other Ph-negative CML patients who do have involvement of 9q34 or the breakpoint cluster region. Since this is the first case of its type to be reported with cytogenetic abnormalities, the clinical relevance of the unique chromosomal rearrangement t(8;17)(p11;q25) in the setting of systemic mastocytosis is unclear. Additional cases need to be reported to determine if this genetic rearrangement is a nonrandom marker of leukemia evolving in a setting of malignant mast cell disease.
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PMID:Mast cell disease followed by leukemia with clonal evolution. 311 98

Antibodies of the immunoglobulin E isotype sensitize mast cells and basophils for antigen-induced mediator release by binding through the Fc portion to a high-affinity receptor (Fc epsilon R1, Ka = 10(9)M-1) on the cell surface causing the clinical manifestations of type I hypersensitivity. As the amino acid sequence of the human epsilon chain is now known, attempts have been made to map the Fc epsilon R1 binding site on IgE to a fragment smaller than Fc epsilon using proteolytic cleavage products, none of which proved to be active. Cleavage between the C epsilon 2 and C epsilon 3 domains released two inactive fragments, suggesting that the junction between these segments could be important in receptor binding. This region is protected against protease digestion in the rat IgE complex with the receptor of rat basophilic leukaemia cells. Here we report the mapping of the mast cell receptor binding site on human IgE to a sequence of 76 amino acids at the C epsilon 2/C epsilon 3 junction. Recombinant peptides containing this sequence inhibit passive sensitization of skin mast cells in vivo and sensitize mast cells to degranulation by anti-IgE in vitro almost as efficiently as a myeloma IgE. Fragments containing the separate domains are inactive. Additional sequences are required for rapid assembly of fragments into disulphide-linked dimers, suggesting that a single chain can form the active site. In a three-dimensional model of the human Fc epsilon, the two identical segments are far apart. Each folds to generate a cleft between the C epsilon 2 and C epsilon 3 domains on the surface of the Fc epsilon. The docking of IgE on to mast cells could take place within this cleft.
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PMID:The mast cell binding site on human immunoglobulin E. 312 93

An antigen identified by murine monoclonal antibody YB5.B8 has previously been detected only on acute non-lymphoblastic leukaemia (ANLL) cells and tissue mast cells. We now report that the YB5.B8 antigen is present on a minor population (up to 3%) of normal bone marrow mononuclear cells which overlaps the set of progenitor cells capable of forming haemopoietic colonies in vitro. The results indicate that the antigen is a normal haemopoietic progenitor cell marker which is selectively retained on mast cells during maturation, and that leukaemias which express the antigen are not necessarily committed to the mast cell lineage. Furthermore, the antibody was capable of partially inhibiting the formation of haemopoietic colonies in vitro, indicating an important functional role for the antigen. This is consistent with the observation, reported in the accompanying paper, that expression of the YB5.B8 antigen is strongly correlated with poor response to therapy in patients with ANLL.
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PMID:A monoclonal antibody to a human mast cell/myeloid leukaemia-specific antigen binds to normal haemopoietic progenitor cells and inhibits colony formation in vitro. 314 4

Cross-linking reagents were used to further characterize the murine B cell receptor for the Fc portion of IgE (Fc epsilon R) and compare this receptor to the well-characterized high-affinity Fc epsilon R on rat basophilic leukemia (RBL) cells. The disulfide cleavable and noncleavable reagents 3,3'-dithiobis(sulfosuccinimidyl) propionate (DTSSP) and bis(sulfosuccinimidyl) suberate (BS3) were used. With these reagents, efficient cross-linking of the alpha component of the high-affinity RBL Fc epsilon R to the membrane-buried beta and gamma components occurred only if the membrane was solubilized before the cross-linking reaction. In studies with purified murine B cells, IgE could be cross-linked to the Fc epsilon R on intact cells with either DTSSP or BS3. Under the same conditions, up to 10% of the B cell surface immunoglobulin (sIg) (both IgM and IgD) was also found to cross-link to a portion of the IgE/Fc epsilon R complex, suggesting that on the intact murine B cell the Fc epsilon R is frequently in close association with sIg. The B cell Fc epsilon R was also examined for the presence of receptor-associated proteins. Under conditions where the high-affinity RBL Fc epsilon R was substantially cross-linked to the alpha, beta, gamma complex, no evidence was seen for similar cross-linking of the B cell Fc epsilon R. Cross-linking experiments on affinity-purified Fc epsilon R preparations also gave no evidence for receptor-associated proteins with the B cell Fc epsilon R, although evidence for receptor-receptor association was seen. Thus, these data further support the concept that there may be little relationship between the high-affinity mast cell/basophil Fc epsilon R and the low-affinity lymphocyte Fc epsilon R.
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PMID:The murine lymphocyte receptor for IgE. III. Use of chemical cross-linking reagents to further characterize the B lymphocyte Fc epsilon receptor. 315 70

The murine B lymphocyte receptor for the Fc portion of IgE (Fc epsilon R) was further characterized by using the membrane impermeable cross-linking reagents 3,3'-dithiobis-(sulfosuccinimidyl) proprionate (DTSSP) and bis-(sulfosuccinimidyl) suberate (BS3). IgE could be cross-linked to the Fc epsilon R on the intact cells with either reagent and, in addition, up to 10% of the B cell surface immunoglobulin (sIg; both IgM and IgD) was also found to cross-link to the IgE/Fc epsilon R complex. Analysis of isolated sIg/IgE/Fc epsilon R complexes indicated that about 60% of the Fc epsilon molecules were becoming cross-linked to sIg. Thus, the data suggest that on the intact murine B cell the Fc epsilon R is frequently in close association with sIg. The murine B cell Fc epsilon R was also examined for the presence of receptor-associated proteins that are buried in the membrane. Advantage was taken of the membrane-impermeant nature of DTSSP and BS3. IgE was cross-linked to the Fc epsilon R on intact cells by using the disulfide-cleavable DTSSP and following solubilization with nonionic detergent; BS3 was used to cross-link possible internal membrane components to the Fc epsilon R. In these experiments, the high-affinity Fc epsilon R on rat basophilic leukemia (RBL) cells could be cross-linked to a nonreducible high molecular weight complex of 100 kilodaltons. However, when intact murine B cells were treated with DTSSP, solubilized and treated with BS3 in the same manner as indicated above, no evidence was found for the presence of membrane-buried receptor-associated proteins with the B cell Fc epsilon R. Thus, these data further support the concept that there may be little relationship between the high-affinity mast cell/basophil Fc epsilon R and the low-affinity lymphocyte Fc epsilon R.
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PMID:Characterization of the low-affinity receptor for IgE on murine B cells by using membrane impermeant cross-linking reagents. 315 82

Changes in the level of intracellular free calcium ([Ca2+]i) are associated with the secretion of mediators of immediate hypersensitivity by rat basophilic leukemia (RBL) cells, a mast cell line. Digital fluorescence ratio imaging of fura-2 was used to measure [Ca2+]i in individual RBL cells. Changes in [Ca2+]i that occurred in response to crosslinking of IgE receptors on the cell surface or to application of the Ca2+ ionophore ionomycin were studied. Stimulation of RBL cells with antigen resulted in rapid increases in [Ca2+]i following lag times that varied widely from cell to cell. Simple averaging of the Ca2+ responses of many cells yielded a gradual response profile that closely resembled that of suspensions of cells measured in the fluorometer. The results show that single cells can respond much more rapidly to antigen than has previously been suggested by studies on populations of cells. The lag time between addition of antigen and initiation of the increase in [Ca2+]i varied considerably between cells in the same field of view. Both the rise time and the variability and average duration of the lag time increased with decreasing antigen concentration.
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PMID:Imaging asynchronous changes in intracellular Ca2+ in individual stimulated tumor mast cells. 316 12

In chronic granulocytic leukaemia, hybridoid leucocytes can regularly be found. Light microscopically they contain a mixture of eosinophilic, basophilic and naphthol AS-D chloroacetate esterase-positive granules. The present study was done to clarify the ultrastructural composition of these cells. It could be clearly shown that in some leukaemic granulocytes primary and secondary eosinophilic as well as basophilic granules occur side by side. There were also basophils with additional tissue mast cell granules. Since normal mast cell granules as well as granules of normal eosinophilic promyelocytes are naphthol AS-D chloroacetate esterase-positive, it would appear possible that mastocytoid as well as primary eosinophilic granules within the leukaemic basophils are responsible for the atypical, granular naphthol AS-D chloroacetate esterase-positivity of these cells. The existence in chronic myeloid leukaemia both of mixed basophilic and eosinophilic granulated leucocytes and of mixed basophilic and mastocytoid granulated leucocytes may suggest a common myeloid precursor of eosinophils, basophils and tissue mast cells. In addition, the hybridoid granulocytes may be considered an expression of a neoplasia-related lineage infidelity.
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PMID:Electron-microscopic characterization of mixed granulated (hybridoid) leucocytes of chronic myeloid leukaemia. 316 78


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