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)

There has been no report on changes in mast cells in hepatic radiation injury. Because of the interactions between mast cells and fibroblasts and mast cell changes in radiation interstitial pneumonitis, we examined the mast cells in experimental hepatic irradiation. We used 60Co gamma-ray in a single dose of 10, 30, 50, and 60 Gy given to the liver area of male Wistar rats. The liver tissue was examined 0.5, 1, 2, 3, 6, 9, and 12 months after irradiation. The mast cells were quantitatively and qualitatively assessed in liver sections by light and electronmicroscopy. Typical chronic liver fibrosis occurred after 30 Gy. As the lesions progressed in severity, the number of mast cells increased and they became larger 1 to 2 months after irradiation. After 3 to 6 months, this change was very marked and degranulation was noted. Both the number and size of mast cells were increased markedly. The peak intensity in mast cell changes paralleled that of connective tissue proliferation. At 12 months, when the fibrous tissue was rich in collagen, the mast cells decreased in number. Our findings suggest that mast cells participate in the development of radiation hepatic fibrosis.
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PMID:The changes and significance of mast cells in irradiated rat liver. 788 41

Chronic allergic diseases and other disorders associated with mast cell activation can also be associated with tissue fibrosis, but a direct link between mast cell mediator release and fibroblast collagen gene expression has not been established. Using in situ hybridization, we show that the elicitation of an IgE-dependent passive cutaneous anaphylaxis (PCA) reaction in mice results in a transient, but marked augmentation of steady state levels of type alpha-1 (I) collagen mRNA in the dermis. While peak levels of collagen mRNA expression in the skin are observed 16-24 h after mast cell activation, substantial numbers of dermal cells are strongly positive for collagen mRNA at 1 and 2 h after antigen challenge, before circulating inflammatory cells are recruited into the tissues. Furthermore, experiments in mast cell-reconstituted or genetically mast cell-deficient WBB6F1-W/Wv mice demonstrate that the increased expression of collagen mRNA at sites of PCA reactions is entirely mast cell dependent. In vitro studies show that the supernatants of mouse serosal mast cells activated via the Fc epsilon RI markedly increase type alpha-1 (I) collagen mRNA levels in mouse embryonic skin fibroblasts, and also upregulate collagen secretion by these cells. The ability of mast cell supernatants to induce increased steady state levels of collagen mRNA in mouse skin fibroblasts is markedly diminished by absorption with antibodies specific for either of two mast cell-derived cytokines, transforming growth factor beta (TGF-beta 1) or tumor necrosis factor alpha (TNF-alpha), and is eliminated entirely by absorption with antibodies against both cytokines. Taken together, these findings demonstrate that IgE-dependent mouse mast cell activation can induce a transient and marked increase in steady state levels of type alpha-1 (I) collagen mRNA in dermal fibroblasts and that mast cell-derived TGF-beta 1 and TNF-alpha importantly contribute to this effect.
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PMID:Promotion of mouse fibroblast collagen gene expression by mast cells stimulated via the Fc epsilon RI. Role for mast cell-derived transforming growth factor beta and tumor necrosis factor alpha. 796 80

Twenty-five psoriatic patients were studied histologically before and after PUVA therapy in order to delineate the relationship between dermal mast cells, psoriasis healing process and collagen changes. A number of mast cells were found in the psoriatic changes. A number of mast cells were found in the psoriatic lesion both before PUVA and also after PUVA therapy in 22 of the 25 patients. Fibrosis of the papillary dermis and upper reticular dermis was found in 3 cases. Increased collagen deposition and increased numbers of fibroblasts were accompanied by verticalization of ectatic and elongated blood vessels, with an overall pattern of relatively recent scarring. Mast cells were no longer detectable in the fibrosis area. We cannot exclude the possibility that PUVA therapy exerts a further stimulus on mast cell histamine and heparin degranulation in this type of psoriasis, thus leading to dermal fibrosis and blood vessel neogenesis.
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PMID:Photofibrosis: a further histopathological change induced by PUVA therapy via the mast cell in guttate psoriasis. Preliminary report. 807 22

Mast cell synovial hyperplasia can occur in patients with rheumatoid arthritis. Histamine can accelerate synovitis and heparin can inhibit lymphocyte function. Since interleukin-4 (IL-4) can stimulate murine mast cell and IgE synthesis, we determined whether mast cell mediators and anti-IL-4 might effect lymphocyte proliferation from patients with rheumatoid arthritis. Twenty-four patients with rheumatoid arthritis and nine normal controls were evaluated by history, physical examination, physician and patient-assessed joint and allergic symptoms, and diary scores. An IL-2-driven-T cell (3H) Tdr proliferation assay with monoclonal anti-IL-4 and a sensitive ELISA were performed with isolated peripheral blood mononuclear cells (PBMC) with 10 micrograms/mL of either concanavalin A (Con A), type I human collagen, or heparin and 10(-6) M histamine. Increased lymphocyte proliferation indices with Con A (mean 21.69 +/- 4.9; 6.54 +/- 3.2 normal controls), type I human collagen (mean 2.17 +/- 0.52; 1.1 +/- .17, normal controls), histamine (mean 1.66 +/- .36; 0.62 +/- 0.08, normal controls), heparin (mean 1.61 +/- .38; 0.69 +/- .11, normal controls) occurred in peripheral blood mononuclear cells from all patients with rheumatoid arthritis compared with normal controls (P < .0236 to .0015) which was inhibited in 32% of peripheral blood mononuclear cells by anti-IL-4. Increased IL-4 ELISA levels in cultured supernatants were noted with heparin (P < .25) and collagen (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased interleukin-4 production in response to mast cell mediators and human type I collagen in patients with rheumatoid arthritis. 815 36

An animal model of radiation-induced lung disease was established using male Wistar rats given sublethal bilateral thoracic irradiation (15 Gy). The rats were studied for up to 20 weeks and compared to sham-irradiated controls. Three distinct syndromes were identified. Two weeks after irradiation there was an increase in wet lung weight without an increase in dry lung weight. Interstitial edema was confirmed ultrastructurally, but aside from minor abnormalities of endothelial cells, both capillary and alveolar basement membranes were intact and there was no alveolar protein leak. At 4 weeks after irradiation, there was an abrupt increase in both wet and dry lung weights, as well as intra-alveolar macrophages, lymphocytes, polymorphs, and protein. These changes persisted for periods of up to 8 weeks. Electron microscopy at 4 weeks revealed prominent interstitial edema and severe endothelial cell damage. There was patchy thickening of the cytoplasm of type I cells as well as some cells which appeared to be transforming from type II to type I cells, suggesting previous epithelial denudation. Mast cell density increased in perivascular and peribronchial areas from 4 weeks, and this and parenchymal mast cell density peaked at 7 weeks. The total collagen content of the lungs (determined biochemically) rose by up to 50% above control values from 5 weeks after irradiation, the bulk of the increase having occurred by 12 weeks. Further increases up to 20 weeks were similar to that seen in growing control animals. Collagen deposition (as defined by electron microscopy and Picrosirius polarization) was prominent in peribronchial and perivascular areas in all animals, but in alveolar walls it was increased severalfold above controls by 20 weeks after irradiation. In summary, this model provides sequential changes of interstitial edema, alveolitis, and interstitial fibrosis which can be studied independently. The temporal relationship between the appearance of mast cells and increased collagen deposition supports the hypothesis that mast cells are intimately related to the development of fibrosis.
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PMID:The pulmonary response to sublethal thoracic irradiation in the rat. 821 Mar 33

We have used a model of bilateral radiation-induced lung disease in the rat to study the effects of corticosteroids. This model is characterized by interstitial edema at 2 weeks after radiotherapy followed by florid alveolitis with an alveolar protein leak which peaks at 4 weeks. Mast cell density peaks at 7 weeks, and there is a progressive increase in lung collagen (fibrosis) from 5 to 20 weeks. Intraperitoneal corticosteroids or saline were given at the time of irradiation or sham irradiation (protocol 1), every second day during weeks 3 and 4 (protocol 2), or three times weekly during weeks 3 to 8 (protocol 3). In protocol 1, steroids protected the lung from interstitial edema at 2 weeks, delayed the alveolitis without reducing its intensity, and significantly reduced the alveolar protein leak. However, radiation fibrosis was not reduced at 20 weeks. Longer steroid administration (protocol 2) suppressed the alveolar protein leak and delayed and significantly reduced the severity of the inflammatory cell response. Although the tissue mast cell and fibrotic responses were suppressed during and for at least 3 weeks after steroids, the ultimate fibrotic reaction was the same in both irradiated groups. In protocol 3, steroids suppressed the alveolitis and delayed the rise in tissue mast cell density, but did not affect the fibrotic response at 20 weeks. These studies suggest that steroids can suppress the alveolitis provided they are used throughout the period of alveolitis. Although they also delay the tissue mast cell response to radiation, the ultimate fibrosis is not altered. This provides further evidence for the dissociation of alveolitis and fibrosis after lung irradiation and has potential implications for management of radiation-induced lung disease in humans.
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PMID:The effect of steroids on radiation-induced lung disease in the rat. 821 Mar 34

Whirl-like structures consisting of strands and bundles of collagen fibres with a central space are described in human breast stroma. Association between these structures and connective tissue mast cells is demonstrated. Mast cells in these whirls, in contrast to those in loose connective tissue, showed signs of secretory activity. On ultramicroscopy some showed electron-dense bud-like structures at the edge of the cell, and between this and adjacent collagen bundles. In the absence of cytoplasmic cover association was demonstrated between the surface of a mast cell granule and a band of collagen fibres in the stroma. In vitro production of collagen fibres was reported in 1952 on the addition of heparin powder to soluble collagen. The mechanism of that reaction was not further defined. Neither, as yet, is that underlying the present findings. The products of mast cell granules would appear to be common to both. It is suggested that these findings may represent an alternative pathway for collagen deposition in vivo, as in vitro.
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PMID:Mast cell association with collagen fibres in human breast stroma. 821 70

Growing evidence in the literature indicates that mast cells are integrally involved in the process of dermal wound repair. They are resident cells of the normal dermis and have several cytokines stored in their granules that are stimulatory to fibroblasts. They also contain serine proteases that may be involved in remodeling of the extracellular matrix during healing. Mast cells are found in increased numbers in acute wounds and in certain chronic fibrotic diseases. Their influence on fibroblast growth and collagen production may be an important element in fibrosis. The effects of mast cell mediators on dermal fibroblasts are currently being explored by our laboratory and others. Myofibroblasts are implicated in the phenomenon of wound contraction. These phenotypically altered fibroblasts express some features of smooth muscle cells, notably actin filaments, and are abundant in granulation tissue. It has been proposed that they are responsible for wound contraction and possibly certain types of contracture. However, this hypothesis has been challenged by studies demonstrating the presence of myofibroblasts in wounds that do not contract, or the process of contraction in vitro in the absence of myofibroblasts. At this time the issue remains open to debate and further research.
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PMID:Mast cell and myofibroblast in wound healing. 822 52

Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.
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PMID:A new model of progressive pulmonary fibrosis in rats. 834 14

We report that embryonic stem cells efficiently undergo differentiation in vitro to mesoderm and hematopoietic cells and that this in vitro system recapitulates days 6.5 to 7.5 of mouse hematopoietic development. Embryonic stem cells differentiated as embryoid bodies (EBs) develop erythroid precursors by day 4 of differentiation, and by day 6, more than 85% of EBs contain such cells. A comparative reverse transcriptase-mediated polymerase chain reaction profile of marker genes for primitive endoderm (collagen alpha IV) and mesoderm (Brachyury) indicates that both cell types are present in the developing EBs as well in normal embryos prior to the onset of hematopoiesis. GATA-1, GATA-3, and vav are expressed in both the EBs and embryos just prior to and/or during the early onset of hematopoiesis, indicating that they could play a role in the early stages of hematopoietic development both in vivo and in vitro. The initial stages of hematopoietic development within the EBs occur in the absence of added growth factors and are not significantly influenced by the addition of a broad spectrum of factors, including interleukin-3 (IL-3), IL-1, IL-6, IL-11, erythropoietin, and Kit ligand. At days 10 and 14 of differentiation, EB hematopoiesis is significantly enhanced by the addition of both Kit ligand and IL-11 to the cultures. Kinetic analysis indicates that hematopoietic precursors develop within the EBs in an ordered pattern. Precursors of the primitive erythroid lineage appear first, approximately 24 h before precursors of the macrophage and definitive erythroid lineages. Bipotential neutrophil/macrophage and multilineage precursors appear next, and precursors of the mast cell lineage develop last. The kinetics of precursor development, as well as the growth factor responsiveness of these early cells, is similar to that found in the yolk sac and early fetal liver, indicating that the onset of hematopoiesis within the EBs parallels that found in the embryo.
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PMID:Hematopoietic commitment during embryonic stem cell differentiation in culture. 841 45


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