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)

To determine the role of heparin in mast cell exocytosis, we studied the effect of heparin on histamine release induced by compound 48/80 or calcium ionophore A23187 in canine mastocytoma cells (BR). Heparin caused concentration-dependent inhibition of compound 48/80-induced histamine release from mast cells (n = 4; P < 0.05) with a mean inhibitory concentration of 0.14 +/- 0.01 U/ml (mean +/- SE). Mean maximal inhibition was 69.3 +/- 2.0%. In contrast, heparin had no effect on calcium ionophore A23187-induced histamine release. Although benzyl alcohol, a preservative of pharmaceutical heparin, had no effect, purified heparin produced a similar inhibitory effect on compound 48/80-induced histamine release (n = 4; P < 0.05). The inhibitory effect of heparin on histamine release was rapid and was eliminated by washing cells. Dextran sulfate, a polysaccharide with negative charge density, produced a similar inhibitory effect on compound 48/80-induced histamine release (n = 4; P < 0.05). We conclude that heparin inhibits compound 48/80-induced exocytosis in mast cells probably by its negative charge density.
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PMID:Heparin inhibits histamine release from canine mast cells. 768 86

The existence of a protein approximately 48% identical with mast cell tryptases was predicted previously from a dog mastocytoma cDNA. Antibodies raised against a peptide based on the deduced sequence suggested that the protein (dog mast cell protease-3, dMCP-3) is expressed in mast cells. In this report, characterization of the protein purified from mastocytomas reveals an N-glycosylated, high molecular weight, tryptic serine protease, which appears to be a tetramer of catalytic subunits, approximately half of which are linked by disulfide bonds. The oligomeric complex yields a single NH2-terminal sequence, which is identical with that predicted by dMCP-3 cDNA. This finding, and the lack of closely related genes on blots of genomic DNA, predict that each subunit is the product of one gene. Although dMCP-3 binds to heparin, it is active and stable at low ionic strength in heparin's absence. It resists inactivation by inhibitors in plasma but is sensitive to small inhibitors, e.g. leupeptin and bis(5-amidino-2-benzimidazolyl)methane (BABIM). dMCP-3 hydrolyzes extended peptidyl p-nitroanilides ending in basic residues, with P1 arginine preferred to lysine; it hydrolyzes the Arg18-Ser19 bond of calcitonin gene-related peptide but cleaves neither vasoactive intestinal peptide nor casein. These data suggest that dMCP-3 is a unique serine protease whose stability, formation of intersubunit disulfide bonds, inhibitor susceptibilities and substrate preferences differ from those of its closest relatives, the mast cell tryptases.
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PMID:Purification and characterization of dog mast cell protease-3, an oligomeric relative of tryptases. 776 12

Mastocytosis is a spectrum of disorders characterized by an aberrant proliferation of tissue mast cells. Although this disease process often affects the skin, it may involve multiple organs. The clinical disorder varies according to patient age, the clinical manifestations demonstrated, and the extent of the mast cell proliferative process. A myriad of clinical symptoms occur, and these may be localized to the organ system involved or may be systemic, depending on whether there is local or generalized mast cell mediator release. Diagnosis includes the demonstration of increased tissue mast cells in involved organs as well as increased levels of biochemical mediators. Patients with cutaneous involvement only have the best prognosis. Treatment is directed toward stabilizing mast cell mediator release and blocking the effects of those mediators generated.
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PMID:Southwestern Internal Medicine Conference: mastocytosis: developments during the past decade. 777 4

Mastocytosis is a rare disease characterized by increase in mast cell numbers. The most frequent organ identified as the site of increased numbers of mast cells is the skin. However, uncontrolled growth of mast cells may occur in many other organs and tissues; this disease is called systemic mastocytosis. Nowadays there are four categories of mast cell disease: 1) indolent mastocytosis, 2) mastocytosis with a hematologic disorder, 3) aggressive mastocytosis, and 4) mast cell leukemia. Although the diagnosis of systemic mastocytosis rests finally on identification of mast cells by histopathological examination of the involved tissues, radiological studies may suggest more decisive tests. In this paper the authors discuss usefulness of different methods of radiological imaging in the diagnostics of mastocytosis.
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PMID:[Systemic mastocytosis: significance of contemporary methods of imaging in diagnosis of this disease]. 793 60

Mast cell activation in vivo is often associated with areas of oedema and connective-tissue degradation. Tryptase and chymase are the major serine proteinases released by mast cells, but they appear to have little activity on most components of the extracellular matrix. The matrix metalloproteinases (MMP) are purported to degrade almost all connective tissue elements and are secreted by cells in the form of inactive precursors. Since the mechanisms of MMP activation in vivo are poorly understood we have examined the potential of mast cell proteinases to activate the precursor forms of human collagenase (MMP-1), stromelysin (MMP-3), gelatinase A (MMP-2) and gelatinase B (MMP-9). Mast cell proteinases prepared from purified dog mastocytoma cells were shown to process and activate purified precursor forms of both MMP-1 and MMP-3. Using antipain and chymostatin, inhibitors for tryptase and chymase, respectively, it was demonstrated that both pMMP-1 and pMMP-3 were effectively processed and activated by the chymase component. By contrast, tryptase activated only pMMP-3. The mast cell proteinases were unable to process or activate purified precursor forms of MMP-2 and MMP-9. However, MMP-3 previously activated by mast cell proteinases was shown to activate pMMP-9, but not pMMP-2. Since we have no evidence that mast cells express these four metalloenzymes, the release of mast cell serine proteinases following activation/degranulation could contribute to local metalloproteinase activation and subsequent matrix degradation.
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PMID:Mast cell proteinases activate precursor forms of collagenase and stromelysin, but not of gelatinases A and B. 803 91

The coexistence of solitary mastocytoma and necrobiotic changes resembling granuloma annulare in the same lesion has not been reported to our knowledge. A 3 1/2-year-old child with a plaque on the arm clinically and histologically consistent with solitary mastocytoma showed characteristic necrobiotic foci indistinguishable from granuloma annulare. We speculate that mast cell degranulation may be involved in the pathogenesis of necrobiosis by altering fibroblast enzyme activity and/or producing prolonged inflammatory reactions.
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PMID:Necrobiosis in solitary mastocytoma: coincidence or pathogenesis? 804 Apr 68

Mastocytosis is a disorder of mast cell proliferation that may appear during infancy, childhood, or adulthood. We studied 67 consecutive patients (33 males, 34 females) with urticaria pigmentosa and assessed them fully to determine the presence of systemic involvement. Ages at onset of lesions ranged from birth to 11 years, with most developing in the first year of life. Pruritus was the primary symptom. Hematologic and serum chemistry profile, radiologic skeletal surveys, and bone marrow aspirations were performed. Slight anemia was present in three patients. Radiologic bone lesions were observed in eight. Bone marrow aspirates showed slight changes in six patients, with only an increased number of mast cells in an additional patient. The disease tended to resolve spontaneously. This prospective study emphasizes the benign nature of pediatric urticaria pigmentosa.
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PMID:Urticaria pigmentosa: a review of 67 pediatric cases. 804 46

In previous work the primary structure of a previously unknown protease was deduced from the sequence of a dog mastocytoma cDNA. The predicted preproprotein shares some features with mast cell tryptases but is no more than 49% identical in sequence to known trypsin-like enzymes, including dog tryptase. This study explores the expression of this protein, termed dog mast cell protease-3 (dMCP-3). A polyclonal Ab was raised to a peptide corresponding to residues 166-181 of the deduced sequence. Anti-dMCP-3(166-181) Ig recognizes dMCP-3 expressed as a CheY fusion protein in Escherichia coli and binds to a approximately 36-kDa protein in extracts of dog mastocytomas. The Ab does not recognize dog tryptase, dMCP-3s closest known relative in mastocytoma cells. When used with fluorescein-conjugated and alkaline phosphatase-conjugated secondary Abs, anti-dMCP-3(166-181) Ig yields punctate cytoplasmic staining in mastocytoma cells, suggesting localization to intracellular granules. Staining is greatly reduced by preincubation with synthetic dMCP-3 peptide, supporting the specificity of the Ab. Immunohistochemical staining of normal dog tissues reveals scattered dMCP-3 reactive cells in skin, intestine, trachea, and lung parenchyma. Double staining with Ab and methylene blue shows that anti-dMCP-3(166-188) Ig recognizes extravascular mononuclear tissue cells with metachromatic granules. In addition, cytoplasmic staining is seen in polymorphonuclear leukocytes within vessels in tissue sections and in leukocytes harvested from blood. Hybridization of dMCP-3 cDNA to dog skin RNA provides further evidence of dMCP-3 gene transcription in normal tissue. Thus, this study provides immunochemical evidence of dMCP-3 expression in dog mast cell tumors, normal tissue mast cells, and neutrophils.
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PMID:Mast cell and neutrophil expression of dog mast cell protease-3. A novel tryptase-related serine protease. 814 4

Mastocytosis is the collective name for a group of clinical syndromes whose signs and symptoms are due to the infiltration of various tissues by mast cells and to the release of chemical mediators by these cells. The skin is the most frequently affected organ. Skin manifestations include urticaria pigmentosa, mastocytoma, diffuse cutaneous mastocytosis and telangiectasia macularis eruptiva perstans. Seven cases of mastocytosis were seen over a 3-year period at the National Skin Centre from 1989 to 1992. All our patients were in the paediatric age group. There were four boys and three girls ranging in age from one year to five years. The mean age of onset of the disease was 2.3 months. Six patients presented with cutaneous signs and symptoms of urticaria pigmentosa and one patient had diffuse cutaneous mastocytosis. Itch was the most prominent symptom seen in all the patients. All the patients had a positive Darier's sign, pathognomonic for mastocytosis. None of the patients had a positive family history. Treatment was conservative and symptomatic, with the use of H1 antihistamines to control itching. A particularly important aspect of management is the avoidance of triggering factors. All our patients have remained well with only skin involvement. The prognosis for children with mast cell disease is good, with at least half of the children with urticaria pigmentosa experiencing reduction of symptoms and lesions by adolescence.
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PMID:Cutaneous mastocytosis in Singapore. 815 91

IgE, IgG and mast cell responses were studied in rats infected weekly with 10 larvae of Nippostrongylus brasiliensis (NB). Worm recovery at 8 weeks of repeated infections was six-fold greater than that of a single infection with 10 larvae, suggesting the accumulation of worms during the repeated infections. Total serum IgE was increased after 2 weeks of infection, and further increased after repeated infections: at 6 weeks of infection the level was four to six times higher than that after a single infection. Anti-NB IgG1 levels were also significantly higher after repeated infections than after a single infection. On the other hand, there was no significant difference in the level of anti-NB IgE between single and repeated infections, as determined by ELISA, as well as by passive cutaneous anaphylaxis (PCA) reaction. Mastocytosis was induced in the small intestine after both single and repeated infections, but the levels did not differ between the two. These results indicate that total IgE and specific IgG1 production are augmented by repeated helminth infections, but specific IgE and mast cell responses are not. This pattern of response may minimize the development of IgE-dependent hypersensitivity reactions with repeated helminth infections.
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PMID:Dissociation of specific and total IgE antibody responses following repeated low-level infections with Nippostrongylus brasiliensis in rats. 832 6


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