Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The kit ligand (KL), also termed stem cell factor (SCF), is a recently discovered hematopoietic growth factor that augments response of early progenitor cells to other growth factors and supports proliferation of continuous mast cell lines. Histological studies suggest that the receptor for SCF/KL, the c-kit proto-oncogene product, is present in bone marrow megakaryocytes. We studied the effects of SCF/KL on immortalized human megakaryocytic cell lines (CMK, CMK6, and CMK11-5) and on isolated human marrow megakaryocytes. Human SCF/KL alone or in combination with the hematopoietic growth factors, interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-6, stimulated proliferation of these megakaryocytic cell lines. SCF/KL treatment did not alter expression of gpIb, gpIIb/IIIa, LFA-1, ICAM-1, or GMP-140 in CMK cells. No effect on ploidy was observed. Furthermore, human SCF/KL induced expression of IL-1 alpha, IL-1 beta, IL-2, and IL-6 in CMK cells. In a fibrin clot system, SCF/KL modestly potentiated megakaryocyte colony formation when added alone to cultures containing CD34+, DR+ bone marrow cells. Addition of SCF/KL with IL-3 or GM-CSF to these cultures resulted in a more marked marrow megakaryocytic cells. SCF/KL may directly affect megakaryocytopoiesis, as well as secondarily modulate hematopoiesis through induction of cytokines in target cells.
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PMID:Effects of the stem cell factor, c-kit ligand, on human megakaryocytic cells. 137 Mar 86

In this study, we have attempted to determine whether mouse peritoneal mast cells released histamine in response to IL-3. Recombinant mouse (m)IL-3 induced histamine release from mouse peritoneal mast cells in a dose-dependent fashion. Histamine release did not occur in the absence of phosphatidyl serine (PS), and was dependent on PS concentrations. The release was 14.3 +/- 3.8 and 43.5 +/- 11.5% (mean +/- SEM, n = 5) at 1 nM IL-3 in the presence of 10 and 20 micrograms/ml of PS. Calcium was required for the response, and in the absence of calcium, significant histamine release was not observed. The kinetics were slower than those of anti-IgE-induced response. IL-3-induced histamine release reached a peak within 15 min, while that by anti-IgE reached 80% of the maximum in 3 min. Lower concentrations of IL-3, which failed to directly induce histamine release, did not enhance anti-IgE-induced histamine release. Other cytokines, including mIL-4, mIL-5, m-granulocyte-macrophage colony-stimulating factor, human (h)IL-1 alpha, hIL-1 beta and hIL-8, neither induced histamine release nor enhanced anti-IgE induced histamine release. IL-4 had no capacity to enhance IL-3-induced histamine release. These results suggest that locally produced IL-3 might modulate mast cell-related inflammation through histamine release from mast cells.
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PMID:Mouse IL-3 induces histamine release from mouse peritoneal mast cells. 138 45

Pairs of monoclonal/polyclonal antibodies directed against interleukin-1 (IL-1) alpha, IL-1 beta and tumour necrosis factor (TNF) alpha were used for immunocytochemical identification of cytokine-containing cells in cryostat sections of human fetal thymuses and thymomas. In the fetal thymus immunoreactivity for IL-1 alpha was mainly confined to the medulla and was detected in S-100 positive interdigitating reticulum cells. The pattern of immunoreactivity for IL-1 beta was similar to that for IL-1 alpha, but the number of positive cells was much lower. Cells positive for TNF alpha were extremely rare in the fetal thymus. In 11 thymomas macrophages were constantly present and were regularly distributed throughout the tumour, whereas S-100 positive interdigitating reticulum cells were fewer and were characterized by a zonal distribution. Thymoma-associated macrophages were negative for IL-1 beta and were poorly reactive for IL-1 alpha, only a few positive cells being detected in five of the cases. Some macrophages with immunoreactivity for TNF alpha were detected in seven cases; they formed rosettes with surrounding lymphocytes or were located in a perivascular position. A marked immunoreactivity for TNF alpha was constantly detected in mast cell granules, which were observed in nine thymomas but not in fetal thymus. Positive immunoreactivity of interdigitating reticulum cells for IL-1 alpha was confirmed in five reactive lymph nodes and was also observed in Langerhans' cells in dermatopathic lymphadenitis. Our findings suggest that IL-1 alpha is a crucial molecule for interdigitating reticulum cell and Langerhans' cell function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Macrophages and interdigitating reticulum cells in normal human thymus and thymomas: immunoreactivity for interleukin-1 alpha, interleukin-1 beta and tumour necrosis factor alpha. 225 68

Conditioned medium (CM) from concanavalin A (Con A)-stimulated murine spleen cells inhibited release of histamine and 5-HT from murine peritoneal mast cells sensitized with monoclonal IgE anti-DNP antibody and challenged with DNP-human serum albumin (HSA) antigen. Inhibition was seen when the CM was added to the mast cells either 24 hr before or simultaneous with, but not 24 hr subsequent to, the IgE, thus showing that inhibition was at the IgE-dependent stage of mast cell sensitization. Unconditioned medium, prepared in the same way as CM but not exposed to spleen cells was without activity, demonstrating that inhibition was due to a spleen cell-derived factor. CM from unstimulated spleen cells was likewise without activity. The sensitization inhibitory factor appears to be a protein, since it was retained upon dialysis, and destroyed by heating at 70 degrees and above. The factor does not appear to be IgE, since it was stable at 56 degrees, and is not IL-1 or IL-2, since recombinant human IL-1 alpha and IL-1 beta, and recombinant mouse IL-1 alpha and IL-2 were without inhibitory activity. The active CM and all recombinant IL-1 and IL-2 preparations did not release histamine or 5-HT directly from mast cells during 48 hr of culture, and did not modulate the histamine content of these cells, nor their capacity to incorporate [3H]5-HT.
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PMID:Conditioned medium from concanavalin A-stimulated spleen cells inhibits the IgE-dependent sensitization of murine peritoneal mast cells in vitro. 231 53

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

1. Our previous work has shown that injection into mice of lipopolysaccharide (LPS) and the cytokines interleukin 1 (IL-1) and tumour necrosis factor (TNF) induces histidine decarboxylase (HDC), the enzyme forming histamine, in various tissues such as liver, lung, spleen and bone marrow, but not in the blood. The induction of HDC also occurs in nude mice and mast cell-deficient mice. On the other hand, haematopoietic cytokines such as IL-3, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) only induce HDC in the haematopoietic organs, i.e. bone marrow and spleen. In the present study, the effect of macrophage depletion on the induction of HDC was examined. 2. On day 1 after a single intravenous injection of a macrophage depletor (liposomes encapsulating dichloromethylene diphosphonate, which is toxic when ingested into macrophages), macrophages were almost completely depleted in the liver and reduced by about 50% in the spleen and bone marrow, but not significantly affected in the lung. On day 3, the degrees of the depletion were similar to those of day 1. In the spleen, macrophages were depleted in the red pulp, and there was a structural destruction. 3. In macrophage-depleted mice, the induction of HDC by LPS, IL-1 alpha or TNF-alpha was not impaired in the liver, and was potentiated in the lung and bone marrow. The induction of HDC was decreased only in the spleen at day 3. 4. HDC was not induced by LPS in the spleen of the adult rat, which is correspondingly inactive in haematopoiesis.5 These results indicate that the major cells in which HDC activity is induced in response to LPS, IL-1 and TNF are not circulating granulocytes, circulating monocytes, T cells derived from thymus, mast cells or phagocytic macrophages. Based on these results, we discuss the possibility that the major cells in which HDC was induced in non-haematopoietic and haematopoietic organs were endothelial cells and haematopoietic precursor cells respectively.
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PMID:Effects of macrophage depletion on the induction of histidine decarboxylase by lipopolysaccharide, interleukin 1 and tumour necrosis factor. 771 16

Mast cell hyperplasia is observed in various inflammatory skin diseases. Although the pathogenesis of these conditions remains largely uninvestigated, it has been speculated that lesional mediators provide a favorable microenvironment for mast cell growth. We investigated the effect of an inflammatory cytokine, IL-1 alpha, on mast cell growth in a mast cell/fibroblast coculture system. When mouse bone marrow-derived cultured mast cells (BMMC) were cultured on a NIH/3T3 fibroblast monolayer, IL-1 alpha stimulated mast cell proliferation. However, IL-1 alpha did not stimulate 3H-thymidine incorporation in BMMC in the absence of fibroblasts. Separation of BMMC from fibroblasts by a permeable micropore membrane reduced the effect of IL-1 alpha. When BMMC were prepared from W/Wv mice, which lack a functional c-kit, or when NIH/3T3 fibroblasts were substituted with Sl/Sld-derived fibroblasts, which lack membrane-bound stem cell factor (SCF), a lower, but significant, effect of IL-1 alpha was observed. Flow cytometric analysis revealed no enhancement of SCF expression on fibroblasts following stimulation with IL-1 alpha. Neutralizing antibodies against IL-3, IL-4, IL-10, and nerve growth factor (NGF) showed no inhibition. On the other hand, indomethacin inhibited the effect of IL-1 alpha, and prostaglandin E2 induced mast cell growth in the co-cultures. These results indicate that IL-1 alpha stimulates mast cell growth by a fibroblast-dependent mechanism, in which SCF/c-kit interaction may participate in a major way. The mast cell growth activity induced by this cytokine can, at least in part, be attributed to prostaglandins. Inflammatory cytokines may thus contribute to mast cell hyperplasia in skin diseases.
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PMID:Interleukin-1 alpha enhances mast cell growth by a fibroblast-dependent mechanism. 1086 12