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 mRNA of Escherichia coli yedU gene is induced 31-fold upon heat shock. The 31-kD YedU protein, also calls Hsp31, is highly conserved in several human pathogens and has chaperone activity. We solved the crystal structure of YedU at 2.2 A resolution. YedU monomer has an alpha/beta/alpha sandwich domain and a small alpha/beta domain. YedU is a dimer in solution, and its crystal structure indicates that a significant amount of surface area is buried upon dimerization. There is an extended hydrophobic patch that crosses the dimer interface on the surface of the protein. This hydrophobic patch is likely the substrate-binding site responsible for the chaperone activity. The structure also reveals a potential protease-like catalytic triad composed of Cys184, His185, and Asp213, although no enzymatic activity could be identified. YedU coordinates a metal ion using His85, His122, and Glu90. This 2-His-1-carboxylate motif is present in carboxypeptidase A (a zinc enzyme), and a number of dioxygenases and hydroxylases that utilize iron as a cofactor, suggesting another potential function for YedU.
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PMID:The crystal structure of Escherichia coli heat shock protein YedU reveals three potential catalytic active sites. 1450 Aug 88

Some "blood substitutes," such as human diaspirin cross-linked hemoglobin DBBF-Hb, can damage the intestinal mucosa. This response may be due to release of free iron from Hb leading to production of reactive oxygen species (ROS). Phosphorothioate oligodeoxynucleotides can bind and sequester iron. Therefore experiments were performed to test whether PS-ODN, composed of ten consecutive cytidines "C-10," reduces Hb-induced ROS generation and damage in the mucosa. Anesthetized Sprague-Dawley rats (4-6 per group) were injected arterially with 1 mg C-10, followed two minutes later by 50 mg DBBF-Hb. The positive controls received only DBBF-Hb and the negative controls either saline or PS-ODN followed by saline. Either ROS formation was monitored using a fluorescence technique, or the intestine was fixed for microscopy after 8 or 30 min. Sixty villi per rat were assigned an epithelial integrity index (EI), ranging from 1 (intact) to 3 (some cell-cell and cell-basement membrane separation). Pretreatment with PS-ODN significantly exacerbated DBBF-Hb-induced ROS formation, and PS-ODN groups showed significantly more epithelial damage near Peyer's patches, (EI of 1.93 +/- 0.06 (SEM) at 8 minutes and 1.31 +/- 0.04 at thirty minutes), than the negative controls, (1.11 +/- 0.02 at both 8 and 30 minutes), or the positive controls (1.43 +/- 0.05 at 8 minutes and 1.20 +/- 0.03 at 30 minutes) (p < 0.05). However, mast cell degranulation, eosinophil accumulation and goblet cell secretion were significantly reduced in the DBBF-Hb groups pre-treated with PS-ODN. Thus, PS-ODN, although an iron chelator, can significantly enhance epithelial damage caused by DBBF-Hb in the rat intestinal mucosa near Peyer's patches, possibly by formation of the ferryl component of the hemoglobin.
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PMID:Effects of phosphorothioate oligodeoxynucleotide on hemoglobin-induced damage to intestinal mucosa. 1596 78

Oxidation state changes of metallic ions are involved in the generation and biological defense against reactive oxygen species. The relationship between allergy and oxidative damage by metallic elements was studied by X-ray fluorescence analysis using a mast cell line. The distribution of metallic elements is changed by the induction of reactive oxygen species. In mast cells, the degranulation leading to antigen or calcium ionophore stimulation is related to excessive accumulation of iron and to its chemical state. X-ray absorption near-edge structure spectroscopy showed that the oxidation state of iron in the cells shifted from Fe(II) to Fe(III) in degranulation. This finding might have implications for understanding the mechanisms involved in IgE-mediated cell responses as seen in allergic reaction.
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PMID:Differentiation, distribution, and chemical state of intracellular trace elements in LAD2 mast cell line. 1632 64

Cumulative evidence suggests that the induction of the antioxidant/anti-inflammatory heme oxygenase (HO)-1 may play a protective role in allergic inflammation. HO-1 suppresses mast cell degranulation and cytokine synthesis. The up-regulation of the HO-1 pathway has a significant protective effect against airway inflammation, mucus hyper-secretion, and hyper-responsiveness in a model of allergic asthma. Moreover, HO-1 inhibits T cell-dependent skin inflammation and differentiation and function of antigen-presenting cells. The precise underlying mechanisms for HO-1-based protection against allergic inflammation are not yet completely understood, but appear to involve the protective effects of HO-1 by-products, such as carbon monoxide (CO), biliverdin/bilirubin and free iron. Among the HO-1 by-products, CO has been shown to mimic some protective actions of HO-1 in allergic inflammations. This article reviews the latest knowledge, recent patent and studies on the protective roles and mechanisms of HO-1/CO in inflammation and allergy.
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PMID:Heme oxygenase-1 and carbon monoxide: emerging therapeutic targets in inflammation and allergy. 1907 5

The origins of repeated hematoxylin shortages are outlined. Lack of integration in the hematoxylin trade exacerbates the problems inherent in using a natural product. Separate corporations are engaged in tree growth and harvesting, dye extraction, processing of extracts to yield hematoxylin, and formulation and sale of hematoxylin staining solutions to the end users in biomedical laboratories. Hematoxylin has many uses in biological staining and no single dye can replace it for all applications. Probably, the most satisfactory substitutes for aluminum-hematoxylin (hemalum) are the ferric complexes of celestine blue (CI 51050; mordant blue 14) and eriochrome cyanine R (CI 43820; mordant blue 3, also known as chromoxane cyanine R and solochrome cyanine R). The iron-celestine blue complex is a cationic dye that binds to nucleic acids and other polyanions, such as those of cartilage matrix and mast cell granules. Complexes of iron with eriochrome cyanine R are anionic and give selective nuclear staining similar to that obtained with acidic hemalum solutions. Iron complexes of gallein (CI 45445; mordant violet 25), a hydroxyxanthene dye, can replace iron-hematoxylin in formulations for staining nuclei, myelin, and protozoa.
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PMID:Hematoxylin shortages: their causes and duration, and other dyes that can replace hemalum in routine hematoxylin and eosin staining. 1956 70

Hair loss (alopecia) can result from a variety of metabolic, endocrine, immunologic, and environmental causes. This investigation was undertaken to determine the mechanisms underlying the sporadic development of alopecia in litters from C57BL/6 interleukin-10-deficient (Il10(-/-)) mice. All pups in affected litters demonstrated alopecia by postnatal days 17-19, with hair loss from their trunks but not from their head, base of tail, or feet. Histopathology revealed distorted hair follicles containing broken hair shafts and prominent dermal infiltrates containing increased numbers of activated mast cells. Hair re-growth began soon after weaning, suggesting that the alopecia was triggered by factors transmitted during lactation. Milk from Il10(-/-) dams induced macrophage secretion of pro-inflammatory cytokines in vitro regardless of whether or not their pups developed alopecia. Feeding dams a diet containing 3-6 ppm iron increased the percentage of litters with alopecia to 100% for pups with mast cells, with 0% alopecia in mast cell-deficient pups. When dams were fed a diet containing 131 ppm iron, significantly lower haemoglobin and hematocrit values were observed in pups from litters with alopecia (71%; 5 of 7 litters) compared to litters without alopecia. Genetic or pharmacologic inhibition of c-kit that resulted in depletion of mast cells in pups prevented hair loss in at-risk litters. These studies demonstrate that maternal iron-restricted diets enhance the incidence of alopecia in IL-10-deficient mouse pups and suggest mast cells as potential effector cells. Further studies are indicated to further explore the mechanisms involved and to determine how mast cells may contribute to alopecia in humans.
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PMID:Alopecia in IL-10-deficient mouse pups is c-kit-dependent and can be triggered by iron deficiency. 2010 Jan 90

The incidence and severity of allergic asthma have increased over the last century, particularly in the United States and other developed countries. This time frame was characterized by marked environmental changes, including enhanced hygiene, decreased pathogen exposure, increased exposure to inhaled pollutants, and changes in diet. Although iron is well-known to participate in critical biologic processes such as oxygen transport, energy generation, and host defense, iron deficiency remains common in the United States and world-wide. The purpose of these studies was to determine how dietary iron supplementation affected the severity of allergic inflammation in the lungs, using a classic model of IgE-mediated allergy in mice. Results showed that mice fed an iron-supplemented diet had markedly decreased allergen-induced airway hyperreactivity, eosinophil infiltration, and production of pro-inflammatory cytokines, compared with control mice on an unsupplemented diet that generated mild iron deficiency but not anemia. In vitro, iron supplementation decreased mast cell granule content, IgE-triggered degranulation, and production of pro-inflammatory cytokines post-degranulation. Taken together, these studies show that iron supplementation can decrease the severity of allergic inflammation in the lung, potentially via multiple mechanisms that affect mast cell activity. Further studies are indicated to determine the potential of iron supplementation to modulate the clinical severity of allergic diseases in humans.
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PMID:Iron supplementation decreases severity of allergic inflammation in murine lung. 2922 Aug 37

Chronic inflammation contributes to remodeling, degeneration, and rupture of saccular intracranial artery aneurysms. Mast cells are important proinflammatory and proangiogenic cells in chronic inflammatory vascular diseases. Here we studied mast cells and neovascularization in 36 intraoperatively resected aneurysms using histology and immunohistochemistry and analyzed the clinical characteristics of the aneurysms according to bleeding status (unruptured vs ruptured). Among the 36 aneurysms, 9 contained mast cells (tryptase-positive cells) and 15 contained neovessels (CD34- and CD31-positive capillarylike structures). The density of neovessels was significantly higher in aneurysm walls containing mast cells than in walls not containing them. In particular, wall areas with abundant mast cells and neovessels also contained iron deposits, indicating damage of newly formed endothelium with ensuing microhemorrhages. Walls with the highest neovessel density and the greatest iron deposition also showed evidence of degeneration. Finally, none of the mast cell-containing aneurysms showed an intact luminal endothelium. Thus, mast cells may adversely affect both neovascular and luminal endothelia. The novel association of mast cells with neovessels and injurious microhemorrhages, as well as with luminal endothelial erosion, suggests that mast cells contribute to remodeling and degeneration of saccular intracranial artery aneurysms.
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PMID:Mast cells, neovascularization, and microhemorrhages are associated with saccular intracranial artery aneurysm wall remodeling. 2510 5

Ferumoxytol is a newly approved preparation of intravenous iron with a modified dextran shell that is thought to confer upon it a low immunogenic potential. Serious adverse reactions have been very uncommon in clinical studies, but these studies excluded patients with prior adverse reactions to other preparations of intravenous iron. Furthermore, the reactions were classified clinically. We report on a patient with a history of hypersensitivity to iron dextran who experienced an anaphylactic reaction after receiving ferumoxytol. Laboratory testing revealed an elevated serum tryptase level, confirming mast cell activation. This is the first laboratory-proven case of anaphylaxis related to ferumoxytol.
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PMID:Anaphylaxis with elevated serum tryptase after administration of intravenous ferumoxytol. 2594 25

Extensive use of superparamagnetic iron oxide nanoparticles (SPIONS) in theranostics prompted us to investigate the acute changes in cell morphology and function following intravenous administration of surface-modified SPIONS in a rat model. Dextran-coated (DEX) and polyethylene glycol-coated (PEG) SPIONS were synthesized and characterized, and cytocompatibility was evaluated in vitro. Haematological, histopathological, ultrastructural and oxidative stress analyses were carried out 24h post intravenous administration in vivo. In test groups, SGPT and SGOT enzymes were significantly altered when compared to saline-only controls. Anti-oxidant imbalance and lipid peroxidation were observed in all major organs. Histology revealed iron-laden Kupffer cells and macrophages in liver and lung respectively. Iron overload was observed in the convoluted tubules of the kidney. Mast cell infiltration and distribution were observed differentially in test groups. Although surface modification of SPIONS improved biocompatibility in vitro, they affected anti-oxidant and tissue nitrite levels, which greatly influenced mast cell infiltration in vivo.
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PMID:Effect of surface-modified superparamagnetic iron oxide nanoparticles (SPIONS) on mast cell infiltration: An acute in vivo study. 2701 27


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