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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased numbers of mast cells are commonly seen at sites of increased bone resorption and in osteoporosis. Long-term administration of heparin, a major component of mast cell granules, causes osteoporosis. We therefore tested the effect of heparin on bone resorption by osteoclasts disaggregated from neonatal rat long bones. We found that, in the absence of serum, heparin was without effect on osteoclast function. However, in the presence of newborn calf serum, rat serum, or bovine platelet-poor plasma-derived serum, heparin, in the range 25-100 micrograms/ml, induced an increase in osteoclastic bone resorption. Heparin appeared to act through binding and enhancement of an osteoclast resorption-stimulating activity (ORSA) present in serum. A number of known factors that show an affinity for heparin, including transforming growth factor-beta, platelet-derived growth factors, insulin-like growth factors I or II, acidic or basic fibroblast growth factors, fibronectin, or laminin, could not substitute for ORSA, suggesting that the activity may represent a novel heparin-binding factor. The ability of glycosaminoglycans (GAGs) and related molecules to enhance resorption was dependent on the degree of sulfation and on their size: The high molecular weight GAG heparan sulfate and polysaccharides fucoidan or dextran sulfate showed a similar effect, while low molecular weight heparin, chondroitin-2-sulfate, chondroitin-4-sulfate, and chondroitin-6-sulfate were without effect. We propose that mast cells or heparin therapy increases bone resorption through augmentation of the activity of a factor involved in the local and systemic regulation of osteoclastic bone resorption.
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PMID:Heparin augments osteoclast resorption-stimulating activity in serum. 204 Jun 55

Myelin basic protein (MBP)-specific SJL/J T cells were cultured in normal growth medium or growth medium supplemented with 10% culture supernatant from WEHI-3 cells, a source of interleukin-3 (IL-3), or with recombinant IL-3. T cell lines cultured with IL-3 supplementation were more encephalitogenic compared to parallel lines cultured without this supplement. There was little difference in antigen-specific proliferative response or expression of cell surface markers CD3, CD4, CD8, IL-2R, or alpha/beta TCR in the parallel lines. Supernatant fluids from antigen-stimulated T cells from each cycle were tested for the presence of IL-2, IL-3, IL-4, granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF alpha/beta) and transforming growth factor-beta (TGF beta). No significant difference in IL-2, IL-4, GM-CSF, TNF alpha/beta, or TGF beta levels were seen when supplemented and unsupplemented cultures were compared. Supernatant culture fluids contained an activity that was highly stimulatory for the IL-3-dependent mouse mast cell line, MC/9. This activity was attributable to a combination of at least three factors that varied in relative concentrations throughout the course of the experiments. Based on neutralization by monoclonal antibodies, MC/9 stimulating activity in early passage lines was attributable entirely to IL-3 and GM-CSF. The fraction of the MC/9 stimulatory activity that could be neutralized by monoclonal antibody to IL-3 decreased with increasing stimulation cycle while the fraction neutralized by anti-GM-CSF antibodies remained relatively constant. At the time that the lines lost encephalitogenicity, the activity neutralizable by anti-IL-3 had dropped to low levels in the culture supernatants; however, MC/9 stimulatory activity remained present in the supernatants. This was due to GM-CSF and a third unidentified factor.
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PMID:Interleukin-3 and encephalitogenic activity of SJL/J myelin basic protein-specific T cell lines. 768 50

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.
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PMID:Regulation of the development of type 2 T-helper cells in allergy. 771 Jul 7

Airway epithelial cells modulate the inflammatory response in asthmatic, allergic and fibrotic lung diseases through the secretion of cytokines that regulate the movement and activation of inflammatory cells. Mast cells play an important role in the pathogenesis of these lung diseases. In this study we report that normal airway epithelial cells express stem cell factor which is a critical mediator of mast cell growth and differentiation and that transforming growth factor-beta inhibits secretion of stem cell factor by airway epithelial cells.
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PMID:Airway epithelial cells produce stem cell factor. 898 73

We previously showed that interleukin-3 (IL-3) alone is not sufficient, although it is essential for murine mucosal-type mast cell development and that prostaglandin E (PGE) and interferon-gamma (IFN-gamma) are critical for survival or differentiation of mast cell precursors. We also confirmed that IL-4 is a key inhibitor for mast cell precursors despite being a growth factor of mast cells. In the present work, mouse spleen cells were cultured with recombinant (r) IL-1 beta, rIL-5, rIL-6, rIL-9, granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), tumor transforming growth factor-beta (TGF-beta), or tumor necrosis factor-alpha (TNF-alpha) in the presence of endogenous IL-3. After 12 days of culture, mast cell development was induced by rIL-6 and rTNF-alpha, rIL-1 beta, rIL-5, rGM-CSF, rTGF-beta and even the mast cell growth factors, rIL-9 and rSCF, failed to induce mast cell development. However, unlike IL-9 and SCF, IL-6 and TNF-alpha did not promote the growth of mast cells already developed. Macrophage may be one of the responsive cells of IL-6 and TNF-alpha in the cultures, because removal of macrophages greatly reduced the mast cell development induced by the cytokines. The actions of TNF-alpha and IL-6 were inhibited by indomethacin, an inhibitor for prostaglandin synthesis, and by neutralizing anti-IFN-gamma and anti-IL-3 antibodies. rIL-4, when added at the start of the culture, also inhibited mast cell development induced by rIL-6 and rTNF-alpha. Nevertheless, neutralizing anti-IL-6 and anti-TNF-alpha antibodies did not suppress mast cell development induced by PGE and IFN-gamma. TNF-alpha and IL-6 enhanced IFN-gamma production, but suppressed IL-4 production in the cultures. Mast cell numbers induced were inversely and directly proportional to IL-4 and IFN-gamma levels, respectively. These results indicate that inflammatory mediators as triggers are important for mast cell development although they are not the mast cell growth factors.
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PMID:Tumor necrosis factor-alpha- and interleukin-6-triggered mast cell development from mouse spleen cells. 900 55

Since data on the ability of human mast cells to produce various cytokines are scanty, we examined the mRNA expression, its modulation and the resulting protein expression of a number of well-characterized cytokines, using semi-quantitative reverse transcription-polymerase chain reaction of cell extracts and enzyme-linked immunosorbent assays for analysis of cell supernatants. One million cells/ml of the human mast cell line HMC-1 were stimulated with 25 ng/ml phorbol myristate acetate (PMA), 5 x 10(-7) M calcium ionophore A 23187 (ionophore) or both stimuli combined for various time periods. Constitutive expression in unstimulated cells was found for interleukin-1 beta (IL-1 beta) -3, -4, -8, tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta). Maximal mRNA up-regulation was observed by 2-4 hr, with a second peak for TNF-alpha at 24 hr. After a 4-hr stimulation, IL-13 expression was detectable as well, whereas for IL-12, only the p35 but not the p40 chain was found, and IL-2, -5, -7 and interferon-gamma (IFN-gamma) were not expressed at all. Large quantities of IL-8, TNF-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-3 were secreted time-dependently over a 72-hr period, with lower levels of IL-1 beta, -6, -10 and TGF-beta and no detectable IL-2, -4 and IFN-gamma protein. When IL-6 and IL-8 expression was compared in more detail, IL-6 mRNA was found to be up-regulated only with ionophore but not PMA, whereas both stimuli alone or combined increased IL-8 mRNA expression. Preincubation with cycloheximide inhibited IL-6 but not IL-8 transcription, and incubation of stimulated cells with actinomycin D stabilized IL-8 and also IL-6 mRNA. These data suggest a selective regulation of distinct cytokines in human mast cells at the transcriptional and post-transcriptional levels. Furthermore, the spectrum of cytokines produced by HMC-1 cells supports the well-recognized role of mast cells in immediate-type hypersensitivity reactions as well as their potential colony-stimulating and tissue-remodelling abilities.
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PMID:Comparative cytokine gene expression: regulation and release by human mast cells. 961 81

We have previously shown that fibroblast and keratinocyte supernatants up-regulate expression of mast cell characteristics in the human immature mast cell line HMC-1. This effect could not be induced in HMC-1 cells by the well-known mast cell growth factor stem cell factor (SCF), probably due to mutations of the SCF receptor c-Kit in these cells. Here we report the effects of several known fibroblast- and keratinocyte-derived growth factors, namely nerve growth factor (NGF), basic fibroblast growth factor, platelet-derived growth factor and transforming growth factor-beta, on mast cell differentiation, using HMC-1 cells as a model. NGF, at 0.1-50 ng/ml concentrations, caused a marked, dose-dependent up-regulation of tryptase, Fc epsilon RI and histamine within 10 days of culture, associated with an enhanced expression of mRNA for Fc epsilon RI and mast cell tryptase. On restriction analysis, only mast cell beta-tryptase, but not alpha-tryptase, could be demonstrated. Furthermore, the high-affinity NGF receptor (TrkA) was found at both the transcriptional and protein levels, while expression of the low-affinity NGF receptor was detectable at the mRNA level only. None of the other growth factors caused a significant alteration of the mast cell markers studied when added to HMC-1 cells at concentrations known to be biologically active in other culture systems. Immature human mast cells are thus induced to assume a more mature phenotype in vitro in response to NGF, most probably via stimulation of the high-affinity NGF receptor expressed on these cells. Besides SCF, NGF should therefore be considered as an additional mast cell growth factor that contributes to human mast cell maturation at tissue sites.
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PMID:Effects of nerve growth factor (NGF) and other fibroblast-derived growth factors on immature human mast cells (HMC-1). 977 35

-Mast cells are present in the human arterial intima. To study whether mast-cell degranulation influences the rate of proliferation of smooth muscle cells, we cocultured sensitized (IgE-bearing) rat serosal mast cells and rat aortic smooth muscle cells (SMCs). When sensitized mast cells were stimulated to degranulate with antigen, the rate of proliferation of the cocultured SMCs decreased sharply. This inhibitory effect was found to be due mainly to the very high molecular weight (Mr) heparin proteoglycans (average Mr 750 000) released from the stimulated mast cells. When the heparin proteoglycans were purified from mast-cell granule remnants and added to the SMC culture, they were found to block the cell cycle at the G0-->S transition and the exit from the G2/M phase, their inhibitory effect resembling that of commercial heparin. However, in contrast to the reported dependence of the inhibitory effect of commercial heparin on the release of transforming growth factor-beta from serum, the inhibitory effect of the mast cell-derived heparin proteoglycans in the presence of serum was not transforming growth factor-beta dependent. Moreover, the effect of the mast cell-derived heparin proteoglycans was more efficient than that of commercial heparins of high (average Mr 15 000) and low (average Mr 5000) molecular weight. We also purified heparin glycosaminoglycans (average Mr 75 000) from the mast cell-derived heparin proteoglycans and found that they also inhibited SMC growth efficiently, although less strongly than their parent heparin proteoglycans. These results reveal, for the first time, that mast cells are able to regulate SMC growth. Thus, activated mast cells, by releasing heparin proteoglycans, possibly participate in the regulation of SMC growth in the human arterial intima, the site of atherogenesis.
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PMID:Heparin proteoglycans released from rat serosal mast cells inhibit proliferation of rat aortic smooth muscle cells in culture. 991 76

Vascular hypertrophy, a feature of experimental and human diabetes, has been implicated in the pathogenesis of the microvascular and macrovascular complications of the disease. In the present study, we sought to examine the role of endogenous endothelin and its relation to vascular growth factors in the mediation of vascular hypertrophy in experimental diabetes and to examine the contribution of mast cells to this process. Vessel morphology, endothelin, growth factor gene expression, and matrix deposition were studied in the mesenteric arteries of control and streptozotocin-induced diabetic Sprague-Dawley rats treated with or without the dual endothelin(A/B) receptor antagonist bosentan (100 mg x kg(-1) x d(-1)) during a 3-week period. Compared with control animals, diabetic animals had significant increases in vessel weight, wall-to-lumen ratio, mast cell infiltration, extracellular matrix deposition, and gene expression of epidermal growth factor (EGF) and transforming growth factor-beta(1). In diabetic, but not control, vessels, not only were EGF mRNA and endothelin present in endothelial cells, but also their expression was observed in adventitial mast cells. Immunoreactive endothelin was present in the media of mesenteric vessels of diabetic, but not control, animals. Bosentan treatment significantly reduced mesenteric weight, wall-to-lumen ratio, mast cell infiltration, matrix deposition, and EGF mRNA but did not prevent the overexpression of transforming growth factor-beta(1) mRNA in diabetic rats. These findings suggest that endogenous endothelin and EGF may play a role in diabetes-induced vascular hypertrophy and that mast cells may be pathogenetically involved in this process.
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PMID:Endothelin receptor antagonism ameliorates mast cell infiltration, vascular hypertrophy, and epidermal growth factor expression in experimental diabetes. 1066 11

In 58 patients with mast cell disease (MCD) and three with basophilic leukemia, bone marrow (54 cases) or skin tissue (four cases) was studied immunohistochemically for expression of Kit (c-kit protein), the different isomers of transforming growth factor-beta (TGF-beta), basic fibroblast growth factor (bFGF), and their respective receptors. Kit was expressed in all cases of MCD but in none of basophilic leukemia. Expression pattern of cytokines and their receptors was variable in systemic MCD with (SMCD-HD) or without (SMCD) associated hematologic disorder. However, type I TGF-beta receptor (TGFbeta1R) was not expressed in 30% of SMCD-HD patients or in patients with mast cell leukemia, but the remaining cases of MCD showed near uniform expression. The associated hematologic disorders in TGFbeta1R-negative cases of SMCD-HD were prognostically less favorable than those associated with TGFbeta1R-positive cases of SMCD-HD. The results confirm the diagnostic value of Kit immunohistochemistry in MCD and suggest a biologically relevant heterogeneity in TGFbeta1R expression among patients with SMCD-HD.
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PMID:Immunohistochemical studies of c-kit, transforming growth factor-beta, and basic fibroblast growth factor in mast cell disease. 1173 6


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