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)

Mouse bone marrow (BM) was cultured in the presence of recombinant mouse (rm) interleukin-3 (IL-3), rmIL-4, rmIL-5, rmIL-7, purified mouse (m) IL-9, rmIL-10, recombinant human (rh) macrophage-colony-stimulating factors (M-CSF), rm granulocyte-macrophage colony-stimulating factors (GM-CSF) rm stem cell factor (SCF), rh interferon-alpha (IFN-alpha), rmIFN-gamma, and mNGF to determine which cytokine would give rise to mast cells in murine BM cultures. From a starting population of 1 x 10(7) cells, 1.55 x 10(7) mast cells developed within 14 days in cultures supplemented by rmIL-3. No mast cells were seen at day 14 when any of the other cytokines were present alone, except for rmSCF, which supported the growth of < 0.01% of mast cells observed in IL-3-dependent BM cultures. When rmIL-4, -5, -7, -10, mIL-9, rhM-CSF, rmGM-CSF, rmSCF, rhIFN-alpha, -gamma, or mNGF were added to BM cultures in the presence of rmIL-3, mast cell growth increased 200% with the addition of rmSCF, and 10% when rmIL-4 or IL-9 was added. However, the addition of rhM-CSF, rmGM-CSF, rmIFN-gamma, and mNGF decreased the number of mast cells. Mast cell number, as determined by metachromatic stains, generally approximated the number of Fc epsilon RI+ cells as assessed by FACS analysis. Among the cytokines, only rmIL-4 and rmSCF were able to support the survival of mast cell progenitors in the absence of obvious mast cell proliferation, similarly to rmIL-3. Only rmSCF alone, or in combination with rmIL-3 or -4, supported the growth of mast cells from mouse peripheral blood mononuclear cells (PBMC) where the number of mast cell precursors was about 90 per 10(6) PBMC. With time, mouse BM cells cultured in rmIL-3 became more responsive to rmSCF. Taken together, these data demonstrate that IL-3 is a major early mast cell growth factor, that mast cells become more dependent on SCF with time, and that the effects of IL-3 and SCF are upregulated (IL-4) or downregulated (M-CSF, GM-CSF, IFN-gamma) by both growth factors and proinflammatory cytokines.
 ...
PMID:Demonstration of differential effects of cytokines on mast cells derived from murine bone marrow and peripheral blood mononuclear cells. 752 67

In the last few years evidence has been accumulated to suggest that allergen-reactive type 2 T helper (Th2) cells play a triggering role in the activation and/or recruitment of IgE antibody-producing B cells, mast cells and eosinophils, the cellular triad involved in the allergic inflammation. Interleukin (IL)-4 production by a still unknown cell type (T-cell subset, mast cell/basophil?) at the time of antigen presentation to the Th cell is critical for the development of Th2 cells. Other cytokines, such as IL-1 and IL-10, and hormones, such as calcitriol and progesterone, also play a favoring role. In contrast, cytokines such as interferon-alpha, interferon-gamma, IL-12 and transforming growth factor-beta, and hormones, such as dehydroepiandrostenone, play a negative regulatory role in the development of Th2 cells. However, the mechanisms underlying the preferential activation by environmental allergens of Th2 cells in atopic subjects still remain obscure. Among the possibilities are alterations to molecular mechanisms directly involved in the regulation of IL-4 gene expression or deficient regulatory activity of cytokines that antagonize Th2 cells.
 ...
PMID:Regulation of the development of type 2 T-helper cells in allergy. 771 Jul 7

We describe the case of a 69-year-old man with systemic mastocytosis and severe osteopetrosis who carries a somatic activating mutation in the c-kit proto-oncogene. The patient initially presented with urticaria pigmentosa, progressing to systemic mast cell disease with severe anemia due to bone marrow involvement, chronic diarrhea, and hepatosplenomegaly. Direct sequencing using amplimers from reverse transcriptase-polymerase chain reactions (RT-PCR) from skin mast cell-derived RNA revealed a point mutation in the c-kit proto-oncogene at position 2468, introducing a new recognition site for the restriction endonuclease HinfI. Treatment with interferon-alpha 2a, prednisone, and erythropoietin was initiated. Subsequently, clinical symptoms improved significantly and hemoglobin levels are now stable at 13 g/dl.
 ...
PMID:c-kit mutation and osteopetrosis-like osteopathy in a patient with systemic mast cell disease. 979 83

The receptor tyrosine kinase Axl which expresses extracellular domains reminiscent of cell adhesion molecules, is involved in homotypic binding as well as in intracellular signaling of myeloid progenitor cells. In order to investigate factors which might influence differentiation pathways through changes of the adhesive properties of cells, we analyzed the expression of axl in immature basophil and mast cell lines and in cultured basophil and mast cell precursors. Axl expression was induced by interferon-alpha in the human leukemic mast cell line HMC-1 and in cultured mast cells derived from CD34+ peripheral blood cells. Axl induction was dose dependent, appeared within 1 h, and was independent of de novo protein synthesis. IFNalpha-treated HMC-1 cells expressing axl formed large cell aggregates within 40 h while untreated cells did not. HMC-1 cells also expressed gas6, the putative ligand of axl, which has been shown to induce axl-mediated homotypic binding. Gas6 expression was independent of interferon treatment in HMC-1 cells. The present results suggest that axl-mediated changes of cellular adhesive properties in mast cells may be important in mast cell differentiation as well as in mast cell-associated inflammation.
 ...
PMID:Regulation and possible function of axl expression in immature human mast cells. 985 44

Human mast cells are multifunctional tissue-dwelling cells that play a crucial role in eosinophil-dependent disorders, such as asthma and parasitic diseases, by the secretion of eosinophil-active mediators. Mast cell-derived cytokines, generated in response to cross-linking of the high-affinity IgE receptor, can regulate eosinophil activation, survival, and chemotaxis. In this study, mast cells generated from human cord blood progenitors (stem cells) were studied for eosinophil-active inflammatory cytokine expression. Cord blood-derived mast cells (CBDMC) expressed typical intracellular scroll granules and microvilli-like structures on their cell surfaces, demonstrated the presence of tryptase, and elaborated prostaglandin D2 (PGD2) after cross-linkage of the high-affinity receptor for IgE (FcepsilonRI). CBDMC expressed tumor necrosis factor-alpha (TNF-alpha) and the eosinophil-active growth factors, interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) after activation. (IL-1beta greatly enhanced IgE-dependent production of these cytokines in response to FcepsilonRI cross-linkage, suggesting a role for bystander/phagocytic cells in modulating mast cell function. In contrast, interferon-alpha (IFN-alpha) inhibited IL-5 and GM-CSF generation, and the glucocorticoid, dexamethasone (Dex), inhibited production of IL-5 and GM-CSF from CBDMC. A macrophage-mast cell-eosinophil axis may exist in vivo that may be susceptible to pharmacologic manipulation.
 ...
PMID:Regulation of eosinophil-active cytokine production from human cord blood-derived mast cells. 1203 46

Aggressive systemic mastocytosis (ASM) is a clonal mast cell disease characterized by progressive growth of neoplastic cells in diverse organs leading to organopathy. The organ-systems most frequently affected are the bone marrow, skeletal system, liver, spleen, and the gastrointestinal tract. Respective clinical findings (so called C-Findings) include cytopenias, osteolysis (or osteoporosis) with pathologic fractures, hepatosplenomegaly with impaired liver function and ascites, and malabsorption. During the past decade several treatment strategies for ASM have been proposed. One promising approach may be combination treatment with interferon-alpha (IFN-alpha) and glucocorticoids. This concept has been based on the notion that systemic mastocytosis involves multilineage hematopoietic progenitors indicating a relationship with myeloproliferative disorders. However, relatively little is known about the quality of responses to IFN-alpha in ASM and the actual response rates. This may be due in part to the fact that disease criteria for ASM have only recently been established, and no response criteria are available. In the current article, we propose surrogate markers and treatment response criteria for patients with ASM. In addition, we have applied these criteria retrospectively to ASM patients described in the available literature. In these analyses, the calculated rate of major response (=complete resolution of C-Findings) in patients treated with IFN-alpha (with or without additional glucocorticoids) amounts to approximately 21%. This confirms clinical activity in some patients for this drug-combination, but also points to the need to search for more effective strategies in the treatment of patients with aggressive mast cell disorders.
 ...
PMID:Aggressive systemic mastocytosis and related mast cell disorders: current treatment options and proposed response criteria. 1268 63

Integrins are expressed on mast cells and constitute an essential prerequisite for the accumulation of the cells at sites of inflammation. In order to clarify a potential contribution of inflammatory cytokines to this process, we have studied the modulation of integrin expression and adhesion of immature human mast cells (HMC-1) to extracellular matrix proteins by interleukin-6, tumor necrosis factor alpha, interferon-alpha and interferon-gamma. Corticosteroids were used for comparison. On fluorescence-activated cell sorter analysis, preincubation of cells for 48 h with different concentrations of interleukin-6 induced a significant, up to 40%, increase of alpha v alpha 5, CD49b (alpha 2), CD49e (alpha 5), CD49f (alpha 6), and CD51 (alpha v). In contrast, different concentrations of tumor necrosis factor alpha, interferon-alpha, interferon-gamma, and dexamethasone (10-8-10-10 M) inhibited expression of adhesion receptors by up to 60%, reaching significance for some but not all integrins. On semiquantitative polymerase chain reaction analysis, interleukin-6, the other cytokines, and corticosteroids significantly modulated expression of alpha1, alpha v and alpha 5 integrin chains at mRNA level. Functional significance of these findings was proven in adhesion assays using fibronectin, laminin, and vitronectin, with interleukin-6 causing significant enhancement of adhesion in all cases, tumor necrosis factor alpha and dexamethasone inducing significant reduction of adhesion to fibronectin and laminin, and interferon-gamma significantly inhibiting adhesion to fibronectin only. Specificity of interleukin-6-induced changes was demonstrated using antibodies against alpha1 and alpha 5 integrins in unstimulated and interleukin-6-prestimulated cells. These data show that interleukin-6 stimulates mast cell adhesion to extracellular matrix and thus allows for the accumulation of the cells at tissue sites by enhancing integrin expression, whereas tumor necrosis factor alpha, interferon-alpha, interferon-gamma, and dexamethasone downmodulate this process.
 ...
PMID:Interleukin-6 enhances whereas tumor necrosis factor alpha and interferons inhibit integrin expression and adhesion of human mast cells to extracellular matrix proteins. 1271 84

We used three to six courses of 2-chlorodeoxyadenosine (2-CdA) (2-h infusion at 0.14 mg/kg per day x 5 days) given over a period of 3-36 months to treat four patients with aggressive systemic mast cell disease (SMCD) that was resistant to interferon-alpha (IFN-alpha). Treatment with 2-CdA resulted in a major response in two patients and a good partial response in one other patient (75% overall response). Treatment was well tolerated and duration of remission in responding patients ranges from 2 months to 4+ years since the completion of treatment with 2-CdA.
 ...
PMID:Treatment of systemic mast cell disease with 2-chlorodeoxyadenosine. 1465 76

Systemic mastocytosis (SM), as opposed to cutaneous-only mastocytosis, implies the presence of neoplastic mast cell infiltration in extracutaneous tissue. Mast cell disease in adults is often systemic and often involves the bone marrow. Typical clinical and laboratory features of SM include urticaria pigmentosa, mast cell mediator symptoms (eg, headache, flushing, lightheadedness, urticaria and pruritus, nausea, diarrhea, abdominal pain, and vasodilatory shock), bone pain (eg, osteoporosis, lytic bone lesions, and fractures), hepatosplenomegaly, cytopenia, eosinophilia, elevated serum tryptase and histamine, and bone marrow fibrosis and angiogenesis. SM may be indolent (no evidence of organ dysfunction), aggressive (presence of organ dysfunction), associated with another often chronic myeloid hematologic disease (SM-AHD), or present as mast cell leukemia or sarcoma. Mast cell-mediator symptoms are treated with histamine antagonists and cromolyn sodium. Indolent SM does not require cytoreductive therapy. Aggressive SM and SM-AHD are managed based on their molecular profile. Recent information suggests that FIP1-like-1-platelet-derived growth factor receptor-alpha(+) SM responds well to imatinib mesylate, whereas interferon-alpha should be considered as a first-line treatment in all of the other cases, including patients with Asp816Val(+) SM. Cladribine has been shown to be effective in patients who develop resistance to interferon treatment.
 ...
PMID:Systemic mastocytosis: current concepts and treatment advances. 1508 68

Mastocytoses are a heterogenous group of diseases characterized by proliferation and accumulation of mast cells in the skin and other organs. They are subdivided into cutaneous mastocytoses; systemic forms, which may appear with or without skin lesions; mast cell sarcomas and extracutaneous, localized, benign mastocytomas. Systemic mastocytoses apart from the skin mainly involve bone marrow, gastrointestinal tract, bones, lymph nodes, spleen and liver. Whereas indolent forms of systemic mastocytosis are mainly treated with antihistamines, glucocorticosteroids and PUVA therapy, the more aggressive forms, including mast cell leukemia, often require cytostatic chemotherapy. A 53-year old patient with beginning "smoldering systemic mastocytosis" failed to respond to high-dose systemic glucocorticosteroids and interferon-alpha. Treatment with cladribine led to an impressive improvement of skin lesions, a significant decrease in tryptase serum levels and stabilization of bone marrow infiltrates.
 ...
PMID:["Smoldering systemic mastocytosis. "Successful therapy with cladribine]. 1524 20


1 2 3 Next >>