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 clinical symptoms of allergy are caused by cellular (IgE-triggered) responses to an allergen. Effector cells of allergy include eosinophil and basophil granulocytes, as well as tissue mast cells. Growth and accumulation, as well as IgE-dependent and independent functions of these cells are regulated by distinct proteohormones and peptides. The hemopoietic cytokines IL-3 (interleukin-3), IL-5 and GM-CSF (granulocyte-macrophage colony-stimulating factor) are involved in the regulation of basophils (and eosinophils), whereas the ligand for c-kit, SCF (stem cell factor) is a mast cell-specific agonist. Basophils and mast cells express high-affinity IgE-binding sites. Allergen binding to IgE on mast cells and basophils, and consecutive cross-linking of IgE receptors is followed by production and/or secretion of inflammatory mediator substances. Specific activation and deactivation of mast cells/basophils in vitro has been demonstrated by use of recombinant cytokines and allergens, and specific haptens or by use of novel drugs, and should lead to epitope-specific diagnosis and better management of allergic diseases in the future.
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PMID:[Effector cells in allergy: biological principles and new pharmacologic concepts]. 750 62

Stem cell factor (SCF) and its receptor (SCFR), a member of the receptor tyrosine kinase III family that is encoded by the c-kit gene, critically regulate several complex biological programs including hematopoiesis, mast cell development, cutaneous pigmentation, and gametogenesis. We show herein that mouse mast cells die rapidly after the withdrawal of SCF in vivo or in vitro, and provide morphological evidence that such mast cells undergo programmed cell death or apoptosis. We also show that when in vitro-derived mouse mast cells maintained in SCF are removed from SCF-containing medium for only 5 or 6 hours, the cells' genomic DNA exhibits the ladder-like pattern of oligonucleosome-sized fragments typical of apoptosis. These findings demonstrate that SCF can regulate the survival of a cellular lineage which expresses the SCFR by suppressing apoptosis. They also identify a mechanism that can result in striking and rapid reductions in the size of tissue mast cell populations without histological evidence of the concomitant induction of a significant inflammatory response.
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PMID:The c-kit ligand, stem cell factor, promotes mast cell survival by suppressing apoptosis. 750 84

The monoclonal antibody, YB5.B8 binds to the second domain of the c-kit proto-oncogene product on human mast cells, a receptor associated with tyrosine kinase activity. This molecule is involved with cell proliferation, maturation and viability as well as cell activation and its natural ligand is stem cell factor (SCF). We have used this antibody coupled to Dynabeads to perform positive affinity enrichment of human lung mast cells. This procedure results in enrichment of mast cells from 2.6 +/- 0.3% to 85.0 +/- 1.6% purity (n = 29) with yields of 41.9 +/- 3.7% (n = 29). As YB5.B8 interacts with the same receptor domain as does SCF, it is important to demonstrate that this procedure does not modify mast cell function. Incubation of mast cells with 1-5000 ng/ml YB5.B8 for 30 min neither induced histamine release nor modulated histamine release induced by anti-IgE. Furthermore, incubation with YB5.B8 did not alter prolonged culture with SCF. Examination of cells enriched using YB5.B8 showed that they had a normal histamine content (3.8 +/- 0.3 pg/cell compared with 3.9 +/- 0.7 pg/cell unpurified, n = 20) and had unchanged behaviour in both histamine secretion and cell survival studies. These studies indicate that YB5.B8 does not influence mast cell function and thus its use in magnetic affinity purification procedures offers a simple and effective method for enriching human mast cell preparations.
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PMID:Assessment of the anti-c-kit monoclonal antibody YB5.B8 in affinity magnetic enrichment of human lung mast cells. 751 Jul 57

We have carried out studies to ascertain whether the histamine-containing, IgE-bearing cells found in the bronchoalveolar lavage (BAL) fluid obtained during the late-phase response following subsegmental antigen challenge of human airways are predominantly basophils or mast cells. Four lines of evidence suggest that most are basophils: (1) The cells fulfill morphologic criteria for light microscopy. (2) Cell surface markers determined by immunofluorescence and flow cytometry revealed that the IgE-bearing cells express the leukocyte antigens Fc gamma RII and the beta 2 integrins, LFA-1 and Mac-1, but do not express the mast cell-associated c-kit receptor for stem cell factor. (3) The late-phase histamine-containing cells in late-phase BAL fluids have the functional characteristics of basophils in their secretory responses to anti-IgE, the f-met peptide, and phorbol ester TPA. (4) The cells have a functional histamine type 2 receptor, a characteristic of basophils, not mast cells. We conclude that basophils infiltrate the lower airways hours after antigen exposure. These cells may be responsible for the mediator release observed at that time.
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PMID:Identification of IgE-bearing cells in the late-phase response to antigen in the lung as basophils. 751 Sep 84

In this report we demonstrate that murine bone marrow cells cultured in either interleukin (IL)-3 or mast cell growth factor (MGF, also known as c-kit ligand and stem cell factor) differentially express cytokine genes. Bone marrow cells cultured in IL-3 differentiate and proliferate, taking on a mucosal mast cell-like phenotype. These cells express the IL-4 gene. Bone marrow cells cultured in MGF take on a connective tissue mast cell-like phenotype and possess transcripts for both of the subunits of the IL-12 cytokine. Bone marrow cells cultured in both IL-3 and MGF express the IL-4 gene at lower levels than that seen for the IL-3 culture alone, but do not possess IL-12 gene transcripts. The level of IL-12 subunit transcripts derived from the MGF-derived bone marrow cells was compared to that found in splenocytes and activated macrophages, the only cells in which IL-12 production has been previously documented. Both of the IL-12 subunit transcripts were found, compared to a beta-actin control, to be present within MGF-derived cells in the same if not higher quantities than the splenocyte or macrophage cultures. Mucosal mast cells have been previously implicated in the development of the T helper type 2 (TH2) T cell phenotype via their expression of IL-4. The finding that the MGF-derived connective tissue-like mast cells possess IL-12 transcripts suggests that the development of the TH1 T cell pathway may be positively influenced by this type of mast cell.
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PMID:Preferential expression of interleukin-12 or interleukin-4 by murine bone marrow mast cells derived in mast cell growth factor or interleukin-3. 751 32

The c-kit proto-oncogene encodes a receptor tyrosine kinase that is known to play a crucial role in hematopoiesis, especially in mast cell growth and differentiation. Although a number of dominant loss-of-function mutations of c-kit gene have been well characterized in mice, rats, and humans, little is known about the c-kit mutations contributing to ligand-independent activation of the c-kit receptor tyrosine kinase (KIT). In a murine mastocytoma cell line, P-815, KIT has been found to be constitutively phosphorylated on tyrosine and activated in a ligand-independent manner. Sequencing of the whole coding region of c-kit cDNA showed that c-kit cDNA of P-815 cells carries a point mutation in codon 814, resulting in amino acid substitution of Tyr for Asp. Murine wild-type c-kit cDNA and mutant-type c-kit cDNA encoding Tyr in codon 814 were expressed in cells of a human embryonic kidney cell line, 293T. In the transfected cells, mutant-form KITTyr814 was strikingly phosphorylated on tyrosine and activated in immune complex kinase reaction regardless of stimulation with a ligand for KIT (stem cell factor), whereas tyrosine phosphorylation and activation was barely detectable in wild-form KIT. The data presented here provide evidence for a novel activating mutation of c-kit gene that might be involved in neoplastic growth or oncogenesis of some cell types, including mast cells.
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PMID:Ligand-independent activation of c-kit receptor tyrosine kinase in a murine mastocytoma cell line P-815 generated by a point mutation. 751 8

IL-3-dependent mast cells undergo apoptosis upon removal of IL-3, an event that is prevented by the addition of stem cell factor (SCF) acting through its receptor c-kit, suggesting that SCF provides a mechanism to allow mast cells to survive and to differentiate in tissues in the relative absence of IL-3. This observation is consistent with the thesis that the microenvironment, in part, controls mast cell number and viability by modulating SCF production and release. The purpose of the present study was to determine whether a second factor, TGF-beta 1, was capable of modifying the SCF-mediated survival pathway. TGF-beta 1 (1 and 10 ng/ml), known to be an important regulator of cell growth and function, did inhibit the SCF-mediated rescue from apoptosis in IL-3-deprived mast cells. TGF-beta 1 exerted its inhibitory effect on SCF-mediated rescue from apoptosis, even when added 4 h after the addition of SCF. In contrast, TGF-beta 1 had no substantial effect on the viability of mast cells that were grown in the presence of IL-3. TGF-beta 1 also had no noticeable effect on viability and proliferation of a growth factor-independent mast cell line. The inhibitory effect of TGF-beta 1 was neutralized by specific anti-TGF-beta mAb. TGF-beta 1 did not affect the expression of c-kit, as determined by using flow cytometric analysis of mast cells labeled with FITC-conjugated anti-c-kit. These results demonstrate how SCF and TGF-beta may act in concert to regulate mast cell numbers under physiologic or pathologic conditions.
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PMID:Transforming growth factor-beta prevents stem cell factor-mediated rescue of mast cells from apoptosis after IL-3 deprivation. 751 44

We have previously reported a method of mast cell induction by long-term culture of mouse spleen cells without using exogenous mast cell growth factor (Z.-Q. Hu, T. Yoshida, and T. Shimamura, J. Immunol. Methods 149:173, 1992). Supernatants recovered from the long-term cultures contain endogenous interleukin 3 and soluble stem cell factor. These were assessed by the capacity of the recovered supernatants to foster the growth of a mast cell growth factor-dependent cell line and by neutralizing antibodies. Besides the soluble factors, cell-to-cell contacts mediated by membrane stem cell factor on splenic stromal cells and c-Kit receptors on mast cells also affect mast cell induction. Different lots of fetal calf serum (FCS) were examined to determine a possible trigger for cytokine production. FCS can be divided into mast cell-inducible and noninducible sera by this process. However, not all FCS lots contain mast cell growth factor. The mast cell-inducible lots contain lipopolysaccharide (LPS) confirmed by a Limulus assay. Polymyxin B can neutralize the mast cell induction activity. Non-mast cell-inducible FCS can be converted to inducible FCS by adding exogenous LPS. The results indicate that LPS as a trigger of cytokine production is responsible for mast cell induction.
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PMID:Effect of lipopolysaccharide on mouse mast cell induction by a splenic cell culture system. 752 Apr 22

Although interleukin-4 (IL-4) in mice is known to augment the proliferation of mast cells and to modulate the expression of certain mast cell protease transcripts, its effect on human mast cells is less well understood. The current study examined the effects of recombinant human IL-4 (rhuIL-4) on stem cell factor (SCF)-dependent fetal liver-derived human mast cells in liquid culture. In no case did rhuIL-4 augment proliferation of mast cells. rhuIL-4 selectively inhibited certain aspects of the development of mast cells in cultures of fetal liver cells with rhuSCF. These include lower numbers and percentages of cells expressing tryptase and surface Kit, smaller cells, and lower contents of cells for tryptase, histamine, and Kit. Development of metachromasia was not attenuated. The downregulation of Kit, the surface receptor for SCF, is probably a critical factor, because cells lacking this molecule would not be able to respond to SCF. In contrast to mast cell progenitors, mast cells already developed in vitro from fetal liver cells are relatively resistant to rhuIL-4, but are still dependent for survival on the presence of rhuSCF.
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PMID:Interleukin-4 inhibits the expression of Kit and tryptase during stem cell factor-dependent development of human mast cells from fetal liver cells. 752 Jul 76

Mast cells may be cultured from human peripheral blood in the presence of recombinant human stem cell factor (rhSCF). The characteristics of the cells in peripheral blood that give rise to mast cells are unknown. Because mast cell precursors in human marrow are CD34+, human peripheral blood mononuclear cells from patients with mastocytosis and normal controls were sorted on the basis of CD34 expression and the positive and negative cell populations were cultured in rhSCF, recombinant human interleukin-3 (rhIL-3), or both for 6 weeks. Cell cultures were examined every 2 weeks for total and mast cell number and cell differential using Wright Giemsa and acid toluidine blue stains and antibodies to mast cell tryptase and chymase, cell-associated histamine, and expression of CD34, c-kit, Fc epsilon RI, and Fc gamma RII using flow cytometric analysis. The ultrastructural anatomy of mast cells was examined by electron microscopy. Peripheral blood CD34+ cells cultured in rhSCF with or without rhIL-3 gave rise to cell cultures consisting of greater than 80% mast cells by 6 weeks. CD34+ cells cultured in rhIL-3 alone did not give rise to mast cells, whereas rhIL-3 plus rhSCF increased the final mast cell number eightfold when compared with cells cultured in rhSCF alone. Mast cells increased concomitantly with a decrease in large undifferentiated mononuclear cells. CD34- cells did not give rise to mast cells. Histamine content per cell at 6 weeks was approximately 5 pg. Electron microscopy of 4-week cultures showed immature mast cells containing predominantly tryptase-positive granules that were either homogeneous or contained lattice structures, partial scroll patterns, or central dense cores and mixtures of vesicles, fine granular material, and particles. The CD34+ population at day 0 expressed Kit (65%) and Fc gamma RII (95%), but not Fc epsilon RI, by fluorescence-activated cell sorter analysis. At 6 weeks, CD34+-derived mast cells exhibited Fc epsilon RI in addition to Kit and Fc gamma RII, and were negative for CD34 antigen. Patients with mastocytosis showed a higher number of mast cells per CD34+ cell cultured compared with normal controls. Thus, the mast cell precursor in human peripheral blood is CD34+/Fc epsilon RI- and gives rise to mast cells in the presence of rhSCF with or without rhIL-3, and the number of mast cells arising per CD34+ cell in culture is greater when the CD34+ cells are obtained from patients with mastocytosis compared with normal subjects.
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PMID:Mast cells cultured from the peripheral blood of normal donors and patients with mastocytosis originate from a CD34+/Fc epsilon RI- cell population. 752 30


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