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)

Human bronchial epithelial cells were isolated from macroscopically normal bronchi obtained from lobectomy specimens. Cells were grown in nutrient F12 medium, and after the third or fourth subculture they were stimulated with arachidonic acid, histamine, leukotrienes (LT) C4, D4, or E4, prostaglandin (PG) D2, anti-IgE, acetylcholine, bradykinin, or phorbol myristate acetate (PMA). Neither mast cell mediators (i.e., histamine, LTC4, LTD4, LTE4, or PGD2) nor anti-IgE stimulated the release of arachidonic acid metabolites from the epithelial cells. However, arachidonic acid, acetylcholine, bradykinin, and PMA stimulated the release of 15-hydroxyeicosatetraenoic acid (15-HETE) as major and prostaglandin E2 (PGE2) as minor products. The maximal release of 15-HETE and PGE2 occurred in 1 h with arachidonic acid stimulation and in 2 h with other stimuli. Arachidonic acid at 30 microM caused the release of 258 +/- 76 ng and 29 +/- 15 ng (n = 12) of 15-HETE and PGE2, respectively, from 10 x 10(6) epithelial cells, whereas acetylcholine, bradykinin, or PMA caused the release of approximately 2- to 10-fold less 15-HETE and PGE2. These results demonstrate that human bronchial epithelial cells selectively generate 15-HETE as the predominant arachidonic acid product and PGE2 as a minor metabolite. The role of bronchial epithelial cells and their mediators in the pathogenesis of bronchial hyperresponsiveness needs further study.
Am J Respir Cell Mol Biol 1989 Sep
PMID:Release of 15-hydroxyeicosatetraenoic acid (15-HETE) and prostaglandin E2 (PGE2) by cultured human bronchial epithelial cells. 251 53

Beta-adrenergic agonists can prevent mediator release from guinea pig pulmonary mast cells. By pharmacologic characterization, this response is mediated through a beta-2 receptor. Structural characterization of this receptor on the lung mast cell, however, has been limited by methods for isolation of this pulmonary cell. In this study, the guinea pig lung mast cell was isolated to greater than 90% purity, and its beta-adrenergic receptor identified by photoaffinity labeling with [125I]iodoazidobenzylpindolol (125IABP) and separation of membrane proteins by SDS-PAGE. We found the guinea pig pulmonary mast cell beta-adrenergic receptor to electrophorese as a heterogeneous protein between 68 and 116 kD. Photoaffinity labeling with 125IABP was protectable by alprenolol and isoproterenol but not by phentolamine and norepinephrine. Using subtype-selective compounds, the pulmonary mast cell receptor was established to be of a beta-2 subtype. This is the first report of the structural identification of a lung mast cell beta-adrenergic receptor and the first report of a beta-adrenergic receptor of approximately 100 kD in mass. This mast cell receptor is considerably larger than the 65 kD beta-adrenergic receptors that have been identified in whole lung and other tissues. Data we have obtained using Northern blot analysis of mast cell RNA suggest a protein message of 45 kD for this beta-adrenergic receptor and a high degree of glycosylation most likely accounts for the large molecular size observed.
Am J Respir Cell Mol Biol 1989 Nov
PMID:Photoaffinity labeling of the guinea pig pulmonary mast cell beta-adrenergic receptor. 256 88

We have previously reported that rats which have been suffering from streptozotocin-diabetes for 4 weeks show a supranormal mast cell mediated mitogenesis in mesenteric windows and in the skin; this late emerging, augmented mitogenic responsiveness appears, to be unaffected by insulin per se. To test whether this increased proliferogenic response is effected by some acquired quality within the tissue rather than a systemic factor in the blood, we studied mast cell mediated mitogenesis in organ-cultured intact mesenteric windows from rats with diabetes of 4 weeks' duration, using a biochemically-defined serum-free growth medium. Mast cells were activated by Compound 48/80 and their secretion was quantified biochemically in terms of histamine release. The mast cell-dependent mitogenic reaction in the predominant, morphologically discrete fibroblasts and mesothelial cells was quantified photometrically using Feulgen-absorption analysis of individual cell nuclei, and by determination of the mitotic index. Both types of target cell responded to a significantly greater degree mitogenically in diabetic compared with control tissue. This finding suggests that a considerable part of the increased mitogenic responsiveness previously observed in diabetic animals in vivo is causally related to some tissue-bound, i.e., cellular and/or extracellular factor(s) acquired during the course of the disease.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Evidence of an acquired increase in mitogenesis in streptozotocin-diabetic rats, apparently relating to some tissue factor. 256 25

Bone marrow trephines from 31 patients with an initial diagnosis of myelodysplastic syndromes (MDS) were examined and analyzed histologically and immunohistochemically. In those cases terminating in overt leukemia (6/31, 19%), the number of bone marrow mast cells was significantly reduced, compared with those which did not evolve to overt leukemia. The bone marrow lymphoid cells that may participate in immunosurveillance against the proliferation of blast cells were also significantly reduced in cases terminating in overt leukemia. However, S-100 protein-positive cells, which include histiocytes and suppressor T-cells, were increased in cases terminating in overt leukemia. The results indicated that examination of the bone marrow to determine the proportions of mast cells and lymphoid cells which may be involved in host defense systems may be useful in predicting the evolution to overt leukemia in MDS. In the present series, patients with a hypocellular marrow (5/31, 16%) did not progress to overt leukemia and had a significantly lower bone marrow reticulin content, a significantly lower megakaryocyte count, a relatively higher mast cell count and a significantly higher lymphoid cell count than those with a normocellular or hypercellular marrow. These findings may reflect the initial features of MDS or, possibly, that hypocellular MDS is an independent entity with a low potential for blastic proliferation.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Bone marrow analysis of the myelodysplastic syndromes: histological and immunohistochemical features related to the evolution of overt leukemia. 256 49

Structural fluctuations of the apoenzyme form of carboxypeptidase A (EC 3.4.12.2) have been evaluated on the basis of molecular dynamics. The Konnert-Hendrickson refined coordinates of 2437 non-hydrogen atoms of the 307 amino acid residues derived from the X-ray structure of the holoenzyme served as the molecular model together with 548 calculated polar hydrogen atoms and 25 buried solvent molecules. Molecular dynamics simulations were carried out at 277 K, and the averaged structural properties of the protein were evaluated for the terminal 20 picosecond portion of a 48 picosecond trajectory. The average atomic displacement from the initial X-ray structure was 2.49 A for all atoms and 1.79 A for C alpha atoms. The average root-mean-square (r.m.s.) fluctuation of all atoms was 0.67 A as compared to 0.54 A evaluated from the X-ray-defined temperature factors. Corresponding r.m.s. fluctuations for backbone atoms were 0.56 A by molecular dynamics and 0.49 A by X-ray. On the basis of these molecular dynamics studies of the isolated molecule, it is shown that amino acid residues corresponding to intermolecular contact sites of the crystalline enzyme are associated with high amplitude motion. All eight segments of alpha-helix and eight regions of beta-strand were well preserved except for unwinding of the five C-terminal residues of the alpha-helix 112-122 that form part of an intermolecular contact in the crystal. Four regions of beta-strand and one alpha-helix with residues adjacent to or in the active site constitute a core of constant secondary structure and are shown not to change in relative orientation to each other during the course of the trajectory. The absence of the zinc ion does not markedly influence the stereochemical relationships of active site residues in the dynamically averaged protein. The extent of motional fluctuations of each of the subsites of substrate recognition in the active site has been evaluated. Active site residues responsible for specificity of substrate binding or splitting of the scissile bond exhibit low simulated motion. In contrast, residues in more distal sites of substrate recognition exhibit markedly greater motional fluctuations. This differential extent of dynamical motion is related to structural requirements of substrate hydrolysis.
J Mol Biol 1989 May 05
PMID:Dynamical structure of carboxypeptidase A. 273 24

Footprint analysis of the 5'-flanking regions of the alpha-amylase 2, elastase 2, and trypsina genes, which are expressed in the acinar pancreas, showed multiple sites of protein-DNA interaction for each gene. Competition experiments demonstrated that a region from each 5'-flanking region interacted with the same cell-specific DNA-binding activity. We show by in vitro binding assays that this DNA-binding activity also recognizes a sequence within the 5'-flanking regions of elastase 1, chymotrypsinogen B, carboxypeptidase A, and trypsind genes. Methylation interference and protection studies showed that the DNA-binding activity recognized a bipartite motif, the subelements of which were separated by integral helical turns of DNA. The alpha-amylase 2 cognate sequence was found to enhance in vivo transcription of its own promoter in a cell-specific manner, which identified the DNA-binding activity as a transcription factor (PTF 1). The observation that PTF 1 bound to DNA sequences that have been defined as transcriptional enhancers by others suggests that this factor is involved in the coordinate expression of genes transcribed in the acinar pancreas.
Mol Cell Biol 1989 Jun
PMID:Identification of a cell-specific DNA-binding activity that interacts with a transcriptional activator of genes expressed in the acinar pancreas. 278 41

Combinations of muramyl dipeptide (MDP) and toxic or detoxified endotoxin induced necrosis and subsequent disappearance of solid Meth A tumors in syngeneic mice. Toxic endotoxin alone was far less effective. MDP and detoxified endotoxin had negligible antitumor effects of their own. These observations were confirmed by histological examination. Neither MDP nor detoxified endotoxin induced significant changes in and around the tumor by 4, 24, and 48 h after intravenous administration when compared with saline treatment. MDP amplified various effects of toxic endotoxin such as the induction of hyperemia, mitotic arrest, mast cell depletion, non-hemorrhagic necrosis and reduction in lymphocyte infiltrates, but did not affect hemorrhagic necrosis or the influx of polymorphonuclear leukocytes. The combination of MDP and detoxified endotoxin lacked the latter two effects, but the other effects were similar to, although slightly less marked than those induced by the toxic combination. Because the degree of hyperemia was proportional to the degree of subsequent non-hemorrhagic necrosis, MDP seems to potentiate necrosis by enhancing mechanisms leading to hyperemia and mast cell mediators might be involved in the latter effect. Lymphocyte influx and the therapeutic outcome are likely to be related, since exclusively therapeutic treatments reduced the influx of these cells.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:Quantitative histology of muramyl dipeptide-potentiated induction of tumor necrosis by endotoxins. 288 95

Numerous mast cells appear in rat pulmonary granulomas associated with infection by the nematode Nippostrongylus brasiliensis. The kinetics and histochemical characteristics of these mast cells were studied and compared with those of intestinal mucosal mast cells. The number of lung mast cells showed a distinct increase 2 weeks after injection and then gradually decreased. In a study using bromodeoxyuridine (BrdU), which is incorporated into cellular DNA at the S-phase, mast-cell labeling was highest 12-13 days after infection, and returned to the normal level 21 days after infection. This indicates that lung mast cells proliferate for only a short time. Intestinal mucosal mast cells showed a similar pattern. A parallel increase in globule leukocytes in the bronchus and trachea was also observed. The proliferating lung mast cells in the early period were stained with alcian blue but were negative for berberine and avidin-biotin-peroxidase complexes (ABC). In a lung extract, type II protease, which has been reported to be confined to mucosal mast cells, increased until the 14th day, and decreased thereafter. This indicates that lung mast cells, at least in the initial stage of proliferation, are similar to intestinal mucosal mast cells in terms of their cell kinetics and histochemical characteristics. However, histochemical studies of mast cells at a later stage of infection showed a different result. After 12 weeks of infection when the mast-cell density was still high, almost all the lung mast cells became positive with berberine and/or ABC, both of which are supposed to be bound to heparin within mast cell granules.(ABSTRACT TRUNCATED AT 250 WORDS)
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:Phenotypic changes in mast cells proliferating in the rat lung following infection with Nippostrongylus brasiliensis. 289 99

The binding sites of rat IgE to mast cell receptor were investigated by the use of proteolytic fragments and a monoclonal antibody to epsilon chain (MARE-1). Three main fragments were characterized by short-time papain digestion of IgE: F(ab')2-E, a fragment related to the C, 4 domain, and an asymmetric fragment corresponding probably to an IgE molecule with one proteolyzed C, 3 domain. Neither F(ab')2-E nor C, 4 could interfere with the binding of IgE to rat mast cells. These two fragments did not show significant polymerization upon heating at 56 degrees C, while large amounts of polymers were produced from whole IgE, MARE-1 monoclonal antibody was found to react neither with F(ab')2 nor with C, 4, thereby suggesting its interaction with the C, 3 domain. MARE-1 was found to inhibit partially (about 55%) the binding of IgE to its receptor. Taken together the results indicate that the binding sites of IgE to rat mast cell receptor are located within the C, 3 domain. In addition, isolation of the C, 4 domain will be useful to evaluate its participation in the affinity of IgE to receptors of other cells such as lymphocytes or macrophages.
Mol Immunol 1987 Feb
PMID:Studies of the IgE binding sites to rat mast cell receptor with proteolytic fragments and with a monoclonal antibody directed against epsilon heavy chain: evidence that the combining sites are located in the C epsilon 3 domain. 295 98

Cells from adult mouse spleens were cultured in WEHI-3 cell-conditioned medium, which contains the lymphokine interleukin-3 (IL-3). Under these conditions, cells grow well for 4 to 8 weeks; the cultures contain a variety of cell types for the first 1 to 2 weeks but are subsequently composed largely of immune mast cells. We found that infection of these cultures with Harvey sarcoma virus (HaSV) profoundly enhanced the growth potential of the cells, resulting in the reproducible isolation of long-term cell lines. These HaSV-infected cells appeared to be phenotypically identical to the immune mast cells found in uninfected cultures as determined by biochemical, immunological, and cytological tests. Although the cells expressed protein p21Ha-ras at levels similar to those in HaSV-transformed fibroblasts, they continued to require IL-3 for growth in vitro. Similar IL-3-dependent, long-term mast cell lines were also cultured from the enlarged spleens present in HaSV-infected mice. These results suggest that high-level expression of an activated Ha-ras oncogene enhances growth in these cells, perhaps by stimulating the progression of the cells into S, without affecting differentiation or altering the requirements for normal growth factor.
Mol Cell Biol 1985 Sep
PMID:Infection of immune mast cells by Harvey sarcoma virus: immortalization without loss of requirement for interleukin-3. 301 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>