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 knowledge about the differentiation of basophilic leukocytes is fragmentary. This report discusses a detailed phenotypic characterization of molecular markers for hematopoietic differentiation in a basophilic leukemia cell line, KU812. The expression of markers for lymphoid, erythroid, neutrophil, eosinophil, monocytic, megakaryocytic, mast cell and basophil differentiation was analyzed at the mRNA level by Northern blots in the KU812 cells, and for reference, in a panel of human cell lines representative of the different hematopoietic differentiation lineages. KU812 was found to express a number of mast cell and basophil-related proteins, i.e. mast cell tryptase, mast cell carboxypeptidase A, high-affinity immunoglobulin (IgE) receptor alpha and gamma chains and the core protein for heparin and chondroitin sulphate synthesis. We found no expression of a number of monocyte/-macrophage or neutrophil leukocyte markers except for lysozyme. From earlier studies, it has been shown that lysozyme is not expressed in murine mucosal mast cell lines. This finding, together with the expression of the mast cell carboxypeptidase in KU812 might distinguish the phenotype of this cell line from that typical of mucosal mast cell lines in rodents. We found a low level of expression of the eosinophil and basophil marker, major basic protein, which might indicate a relationship between basophils and eosinophils. No expression is, however, detected with the eosinophil-specific markers eosinophil cationic protein, eosinophil-derived neurotoxin or eosinophil peroxidase. We also report an extensive screening for inducers of basophilic differentiation of the KU812 cells. The most efficient protocol of induction included serum starvation which led to a dramatic increase in a number of markers specific for mast cells and basophils such as tryptase, carboxypeptidase A and the heparin core protein. Finally, diisopropylfluorophosphate analysis of total protein extracts from KU812 show four labeled protein bands with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that this cell line expresses at least three previously undescribed serine proteases of which one or more could be a potential basophil-specific marker(s).
 ...
PMID:Phenotypic characterization of KU812, a cell line identified as an immature human basophilic leukocyte. 163 3

It has been demonstrated that the rejection of Hymenolepis diminuta by the mouse is characterized by a humoral response in serum and intestinal lavage. Now the response is also shown to be accompanied by a mast cell and eosinophil response in the lamina propria of the intestine. The mast cell response is, in time and place, correlated with the rejection process of H. diminuta. With regard to the number of eosinophils in the lamina propria, a significant response was only found in the second half of the intestine. The eosinophil peroxidase (EPO) concentration in the intestinal lumen is correlated with the rejection of the parasite and illustrates the involvement of eosinophils in the rejection process. The course of the EPO response is identical to the mast cell response. This, together with other results, suggests that, as to other "systemic" worm infections, a mast cell-eosinophil response may be, at least in part, responsible for the rejection of H. diminuta from the intestinal lumen.
 ...
PMID:Hymenolepis diminuta: intestinal mast cell and eosinophil response of the mouse to infection. 214 15

Mast cells, when incubated in vitro with hydrogen peroxide (H2O2) and iodide, are cytotoxic to schistosomula of Schistosoma mansoni, as determined morphologically by dye exclusion, motility, and refractility and by transmission and scanning electron microscopy. When intact mast cells were incubated with schistosomula, mast cell degranulation with extracellular release of mast cell granules (MCG) was only observed in the presence of added H2O2 (10(-4) M). The secreted MCG, which contain small amounts of endogenous peroxidase activity, adhered to the surface of schistosomula. By 15 to 30 min, the mast cell-H2O2 system in the presence of iodide (10(-4) M) produced marked disruption of the tegumental and internal structures of the schistosomula. No helminthic damage was noted if any component of the incubation mixture (mast cells, H2O2 or iodide) was omitted. MCG could substitute for intact mast cells in the H2O2 and iodide-dependent cytotoxic system; MCG-mediated killing of schistosomula was inhibited by the hemeprotein inhibitor azide, suggesting that the cytotoxic reaction required endogenous peroxidase. The cytotoxicity was increased by eosinophil peroxidase bound to the MCG surface. These findings suggest a mechanism by which mast cells may contribute to the host cytotoxic response to helminths. H2O2 formed by nearby inflammatory cells may induce mast cell secretion, and the released MCG, through their endogenous peroxidase content (or bound eosinophil or neutrophil peroxidase), may react with H2O2 and a halide to form a system toxic to the adjacent helminth.
 ...
PMID:Mast cell-mediated toxicity to schistosomula of Schistosoma mansoni: potentiation by exogenous peroxidase. 242 71

It has been previously demonstrated that eosinophil peroxidase (EPO) when supplemented with hydrogen peroxide and a halide induces noncytotoxic mast cell degranulation. Using a more highly purified EPO preparation, the ultrastructure of EPO-induced mast cell secretion has been studied using transmission and scanning electron microscopy and freeze-fracture techniques. At relatively low EPO concentrations, secretory changes were comparable to those caused by other mast cell secretagogues. Swollen and less electron-dense granules were seen in intracellular channels, some of which opened to the outside of the cell. EPO stimulation led to bulging of the surface membrane by submembranous granules and formation of pores in the cell surface that also contained fewer villous projections than control cells. During the secretory process, plasma membrane bulges were depleted of intramembranous particles in both the E and P faces of the apical regions of the perigranular and plasma membranes. Higher EPO concentrations caused a marked cytotoxic disruption of the mast cells. Diaminobenzidine cytochemistry was used to detect EPO reaction products on the mast cell surface by scanning electron microscopy; this technique should prove useful in detecting peroxidase reaction products on a variety of target cells.
 ...
PMID:Ultrastructure of mast cell degranulation induced by eosinophil peroxidase: Use of diaminobenzidine cytochemistry by scanning electron microscopy. 642 Apr 61

Mast cells, when supplemented with H2O2 and iodide, are cytotoxic to mammalian tumor cells as determined by 51Cr release, and transmission and scanning electron microscopy. H2O2 at the concentration employed (10(-4) M) initiates mast cell degranulation, and mast cell granules (MCG), which contain a small amount of endogenous peroxidase activity, are toxic to tumor cells when combined with H2O2 and iodide. This toxicity is greatly increased by binding eosinophil peroxidase (EPO) to the MCG surface. Each component of the mast cell, MCG, or MCG-EPO system was required and toxicity was inhibited by the addition of the hemeprotein inhibitors azide or aminotriazole, which is compatible with a requirement for peroxidase in the cytotoxic reaction. A sequence of reactions is proposed in which mast cells, stimulated to release their granules by H2O2 generated by adjacent phagocytes, react with H2O2 and a halide to damage tumor cells. EPO release from eosinophils may contribute to this sequence of reactions, both by stimulation of H2O2-induced mast cell secretion and by combination with MCG to form a complex with augmented tumoricidal activity. These rections may play a role in the host defense against neoplasms.
 ...
PMID:Mast cell-mediated tumor-cell cytotoxicity. Role of the peroxidase system. 725 7

Endogenous peroxidase has been reported in rat peritoneal mast cells and granules. Mast cell granules have also been shown to avidly bind exogenous eosinophil peroxidase. To examine the possibility that contaminating eosinophil peroxidase contributes to the reported rat mast cell peroxidase activity, mast cells were increasingly purified over sequential Percoll gradients. Such repeated centrifugations did not affect the histamine content of the cells or the secretory activity of cells, but the small increases in mast cell purity significantly reduced the specific activity of peroxidase; the remaining peroxidase activity of the mast cell fraction was in a range that could easily be accounted for by a small extent of contamination with eosinophils. An upper limit of 0.3 ng peroxidase/10(6) mast cells was determined from these measurements, ten times less than the values previously reported. When isolated mast cells were deliberately contaminated with soluble eosinophil peroxidase followed by granule isolation, the granules showed increased peroxidase activity, confirming the ability of mast cell granules to bind exogenous peroxidase.
 ...
PMID:Eosinophil peroxidase accounts for most if not all of the peroxidase activity associated with isolated rat peritoneal mast cells. 751 May 60

Clinical studies of vernal keratoconjunctivitis (VKC) patients show that total IgE serum levels are increased even in the absence of IgE antibodies to common allergens. Activated eosinophils are also a constant feature of VKC at both the circulation (cytofluorimetry) and tissue (tear cytology and conjunctival scrapings) levels. Moreover, allergen challenge induces a prolonged inflammatory reaction with a prevalent participation of eosinophils, lymphocytes and possibly basophils. Immunohistochemical studies of VKC biopsies show a multicellular inflammatory infiltrate with prevalence of activated eosinophils, mast cells and CD4 lymphocytes in both epithelium and subepithelium. Mediator studies indicate that eosinophil products (eosinophil peroxidase, eosinophinal cationic protein and eosinophil-derived neurotoxin/eosinophil protein X) are increased in both serum and tears, where tryptase and interleukin (IL)-5 are also detectable in higher amounts than in controls. On the basis of these findings, we postulate that VKC can represent a phenotypic model of up-regulation of the cytokine gene cluster on chromosome 5q which through its products (IL-3, IL-4, IL-5 and granulocyte/macrophage-colony-stimulating factor) regulates Th2 prevalence, IgE production as well as mast cell and eosinophil growth and function in VKC.
 ...
PMID:Vernal keratoconjunctivitis: a model of 5q cytokine gene cluster disease. 761 25

Mast cells are important effector cells in IgE-mediated acute allergic reactions. Mast cells also produce cytokines such as interleukin (IL)-3, IL-4, IL-5, tumor necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) that regulate the function of eosinophils and the development of a late-phase inflammatory response to antigen challenge. To evaluate the role of mast cells on the development of IgE-mediated allergic pulmonary eosinophilia in vivo, we compared the eosinophil infiltration into lungs of mast cell deficient mice (WBB6F1/J-W/Wv) with their congenic normal littermates (W/W+). Mice were sensitized with alum-precipitated ovalbumin and challenged with aerosolized ovalbumin on day 12 after sensitization. Bronchoalveolar lavage (BAL) fluid, lung tissue biopsies, and blood samples were collected after ovalbumin challenge. Eosinophil numbers in the BAL and lung tissue, lung eosinophil peroxidase (EPO) activity and serum levels of IgE and IgG1 were measured. In sensitized W/W+ mice, there were increased numbers of eosinophils in the BAL fluid and lung tissue, and EPO levels were increased after ovalbumin challenge. Ovalbumin challenge of sensitized mast-cell-deficient mice produced fewer numbers of eosinophils in the BAL fluid and lungs, and EPO levels were also reduced compared with their challenged congenic littermates. On the other hand, levels of serum IgE and IgG1 were not different between W/Wv mice and their congenic littermates.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Mast cells modulate allergic pulmonary eosinophilia in mice. 769 19

Mast cell-eosinophil interactions in allergy have not yet been completely defined. To determine whether mast cells influence eosinophil survival, human peripheral blood eosinophils were incubated with rat peritoneal mast cell sonicate. After 3 days, viable eosinophils in medium were 21.3% compared with 44% with mast cell sonicate. Like sonicate, supernatants of compound 48/80-activated mast cells enhanced eosinophil survival, demonstrating that the factor(s) involved is stored preformed and rapidly released. Increased eosinophil survival was due to an inhibition of apoptosis (morphologic analysis; annexin V/PI). Neutralizing Abs to granulocyte-macrophage CSF (GM-CSF), but not to IL-3 or IL-5, decreased by 61.7% the enhancing effect on eosinophil viability. Eosinophils are the source of GM-CSF since its release in the culture medium was inhibited by their incubation with the mast cell sonicate together with dexamethasone. In addition, eosinophils incubated with the sonicate expressed mRNA for GM-CSF. To partially characterize the mast cell-derived factor(s) increasing eosinophil survival, the sonicate was heated (56 degrees C/30 min or 100 degrees C/10 min) or preincubated with antihistamines or with anti-TNF-alpha-neutralizing Abs. Most of the activity was heat labile. TNF-alpha was found to be predominantly (70%) responsible, while histamine had no role. Mast cell sonicate also caused eosinophils to release eosinophil peroxidase and to display morphologic signs of activation. In conclusion, we have demonstrated that mast cells enhance eosinophil survival in part through their activation to produce and release the autocrine survival cytokine GM-CSF.
 ...
PMID:Mast cells enhance eosinophil survival in vitro: role of TNF-alpha and granulocyte-macrophage colony-stimulating factor. 960 60

Recent reports describe the beneficial use of lodoxamide, an anti-allergic compound, for the treatment of asthma and allergic conjunctivitis. Lodoxamide is known as a mast cell stabilizer, however, the association of a significant clinical improvement with a specific decrease in eosinophil infiltrate suggested possible direct effects of lodoxamide on eosinophils. The chemotactic response of eosinophils to fMLP as well as to IL-5, in vitro, was very significantly and dose-dependently inhibited by Lodoxamide. Lodoxamide was also able to strongly inhibit the release of eosinophil peroxidase after IgA-dependent activation and, to a lesser extent, the release of eosinophil cationic protein and eosinophil-derived neurotoxin. Moreover, the release of cytotoxic mediators evaluated in an antibody-dependent cytotoxicity assay against parasitic targets was also significantly reduced, not only in the case of human eosinophils but also in a rat eosinophil-mast cell model of cytotoxicity. Taken together, these results indicate that lodoxamide can exert potent inhibitory effects on eosinophil activation in vitro combined with a strong inhibition of eosinophil attraction, leading therefore to a reduction in their pathological potential in vivo.
 ...
PMID:Inhibitory effects of lodoxamide on eosinophil activation. 965 7


1 2 3 Next >>