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)

We compared the time course of histamine release with other markers of intestinal injury in a rabbit model of necrotizing enterocolitis. Injury was induced by luminal acetic acid (200 mM) and casein (10 mg/ml) and experiments terminated after 45 min or 3 hr. Compared to saline controls there was a significant elevation of epithelial permeability (51Cr-EDTA clearance) and luminal protein levels at both time points. Luminal fluid histamine levels were approximately 120-fold greater than saline controls at 45 min but were indistinguishable from control values at 3 hr. We conclude that although mast cell activation is a characteristic of this model, elevations in histamine levels are transient.
Agents Actions 1991 Sep
PMID:Histamine is a transient marker of small intestinal injury induced by luminal acetic acid and casein. 179 25

Melittin (MLT) (10 micrograms/paw) and D49 (0.4 micrograms/paw) were injected into the hind paw of male CD-1 mice and elicited 70-80% of maximal paw edema responses at 60 and 30 min after injection, respectively. D49 paw edema was significantly inhibited by anti-histamine/serotonin agents, a PAF antagonist, a PLA2 inhibitor, and some but not all 5-LO and CO inhibitors, indicating that this edema is produced by several classes of inflammatory mediators with mast cell degranulation apparently playing a major role. In contrast, MLT paw edema was not inhibited effectively using the same pharmacological agents except theophylline, suggesting it was elicited via a different sequence of inflammatory events. In summary, D49 and MLT paw edema models were found to be ineffective models to identify experimental PLA2 compounds in our laboratory.
Agents Actions 1991 Sep
PMID:Comparison of antiinflammatory and antiallergic drugs in the melittin- and D49 PLA2-induced mouse paw edema models. 179 58

Systemic mastocytosis is a rare condition in which mast cells infiltrate various organs, including the skeleton. Because the mast cell secretes various bioactive substances that may induce bone resorption, this condition may cause generalized osteoporosis. We describe a case of a 28-year-old woman who presented with a painful thoracolumbar kyphosis due to generalized osteopenia and multiple pathological compression fractures and was found to have mastocytosis. She underwent operative stabilization of her kyphotic deformity with anterior interbody fusion and posterior Cotrel-Dubousset (CD) instrumentation and fusion. We conclude that mastocytosis should be suspected in an atypical case of so-called idiopathic osteoporosis.
J Spinal Disord 1991 Sep
PMID:Systemic mastocytosis presenting with severe spinal osteopenia and multiple compression fractures. 180 68

Immune complex-induced injury is an important pathogenic factor in antibody-mediated nephritis, systemic lupus erythematosus, rheumatoid arthritis, and other diseases. In this study we investigated the role mast cells in immune complex-mediated injury in mouse skin. Reverse Arthus reaction was induced in mast cell-deficient WBB6F1-W/Wv mice and their congenic controls (WBB6F1(-)+/+). Serial skin sections were evaluated for neutrophil infiltration, edema, and hemorrhage. In WBB6F1-W/Wv mice the neutrophil influx was only 40% and edema 60% of that in congenic controls. Hemorrhage was also significantly reduced in the mast cell-deficient mice. After mast cell reconstitution, the magnitude of the reaction in WBB6F1-W/Wv was equivalent to that in WBB6F1(-)+/+ mice. Mast cell release in reverse Arthus reaction was evaluated by measuring fluorescence intensity after avidin-FITC staining of mast cell granules. There was a 70% decrease in fluorescence intensity. The 5-lipoxygenase inhibitor A-63162 significantly decreased neutrophil accumulation (40%), edema (60%), and hemorrhage in WBB6F1(-)+/+, but not in mast cell-deficient mice. Mast cell reconstitution of WBB6F1-W/Wv mice restored the effect of A-63162. The results indicate that mast cells and their mediators, including leukotrienes, make an important contribution to reverse Arthus reaction.
J Clin Invest 1991 Sep
PMID:Augmentation of reverse arthus reaction by mast cells in mice. 183 74

The possibility that the ml muscarinic receptor subtype can induce release of intracellular granules and transmitters was studied by transfecting a cultured mast cell line. RBL-2H3 cells, with the ml receptor gene. Comparisons were made between carbachol- and antigen-induced activation of various secretory responses. Like antigen, carbachol stimulated inositol phospholipid hydrolysis and release of arachidonic acid with concomitant dose-dependent secretion of granular contents. Carbachol also stimulated a biphasic increase in intracellular calcium, as measured by single cell fura-2 measurements. Although the kinetics of the carbachol-induced rise in intracellular calcium differed from that induced by antigen, they both utilized the same intracellular pool of calcium, and the second phase of the rise in intracellular calcium was dependent on extracellular calcium in both cases. Thus, the ml muscarinic receptor activates release of granules by a mechanism ostensibly similar to that of antigen.
FEBS Lett 1991 Sep 02
PMID:Carbachol induces secretion in a mast cell line (RBL-2H3) transfected with the ml muscarinic receptor gene. 183 47

Plutonium-239 or 241Am administered intravenously in the monomeric citrate form was initially deposited in beagle livers principally in the hepatocytes and to a much lesser extent in the sinusoidal macrophages and connective tissues. The initial distribution was quite uniform throughout the hepatic parenchyma; however, at later postinjection intervals, depending on the amount of injected activity, the liver burden became increasingly more focal due to: (1) a progressive shift of the radionuclide from the hepatic epithelium to the macrophages; (2) the movement of such macrophages toward the portal or central regions of the lobule; and (3) the displacement of the older more radioactive tissue by regenerating hepatocytes, which generally have a much lower radionuclide content. The hepatic lesions produced by Pu or Am included: (1) necrosis and degenerative changes that were clinically serious or fatal in some of the animals injected with approximately 107 kBq kg-1; (2) marked structural and circulatory changes resulting from necrosis and focal hepatocyte hyperplasia; (3) a significant incidence of both benign and malignant primary liver tumors. In both Pu- and Am-treated dogs, the most frequently appearing neoplasm was the bile duct adenoma, followed by the cholangiocarcinoma. The most obvious difference between Pu- and Am-induced liver neoplasia was the greater frequency of fibrosarcomas and mast cell sarcomas in the Am-treated groups. Hepatomas were of relatively low frequency in animals with Pu or Am burdens. Although the incidence of bone neoplasia was high among the dogs in these studies, the risk of liver tumors, especially in the Am-treated animals, exceeded that of the skeleton in some of the lower dosage levels where the survival times were long. A risk coefficient of approximately 1200 fatal liver malignancies (10(4) beagle Gy)-1, derived from the dosage groups with long survival times, was calculated for combined Pu and Am animals. The prominence of the liver syndromes in beagles with burdens of Pu or Am indicates that humans with body burdens of 239Pu, 241Am, or other actinide elements may be at risk from radiation effects in the liver, including neoplasia development.
Health Phys 1991 Sep
PMID:Plutonium- or americium-induced liver tumors and lesions in beagles. 188 23

Mast cells are secretory cells strategically located in the vicinity of blood vessels where they can readily initiate and modulate various inflammatory processes, including plasma exudation and leukocyte infiltration. We have previously shown that 50% of the neutrophil influx during immune complex peritonitis in mice is due to mast cells. Eicosanoids are important mediators of various inflammatory processes including neutrophil infiltration. The possibility that mast cells are essential for the production of leukotrienes (LT) involved in the elicitation of neutrophils in immune complex peritonitis was investigated in mast cell-deficient, WBB6F1-W/WV, and normal, WBB6F(1-)+/+, mice. The time course and amounts of immunoreactive PGE2, 6-keto-PGF1 alpha, and TX3B2 released into the peritoneal exudates were similar in both sets of mice. LTB4 and LTC4 levels, however, were twofold higher in +/+ than in W/WV mice 2 h after stimulation. HPLC analysis of the peritoneal exudate confirmed the presence of leukotrienes. The 5-lipoxygenase inhibitor A-63162 blocked leukotriene production in a dose-dependent manner in both sets of mice. However, this compound caused a significant reduction (60%) of neutrophil infiltration only in WBB6F(1-)+/+ but not in the mast cell-deficient mice. Mast cell reconstitution of WBB6F1-W/WV mice restored the effect of A-63162 on PMN recruitment. These data suggest that mast cells in the vicinity of blood vessels are important for the synthesis of leukotrienes responsible for PMN recruitment.
J Immunol 1991 Sep 01
PMID:Mast cells are critical for the production of leukotrienes responsible for neutrophil recruitment in immune complex-induced peritonitis in mice. 188 Apr 19

The present study was conducted to investigate whether a single administration of a relatively low dose of 8-methoxypsoralen (8-MP) with long-wave ultraviolet A (UVA) irradiation alters human skin test responses to a mast cell secretagogue, codeine, and to a vasodilator, histamine. Administration of 8-MP at a dose of 10 mg followed by UVA irradiation (1 joule/cm2) suppressed the skin flare-and-wheal response to codeine and decreased the number of visible degranulated mast cells in biopsy specimens examined histologically. UVA irradiation alone enhanced the skin wheal-and-flare response to either codeine or histamine. The inhibitory effect of 8-MP plus UVA irradiation on both wheal-and-flare responses to codeine tended to decrease, and an increasing enhancement of the skin response to histamine could be observed as the dose of 8-MP was increased from 10 to 30 mg. We postulate that (1) a single 8-MP plus UVA irradiation treatment at appropriate doses could be a potential approach to modulate the mediator-releasing properties of mast cells resident in the skin and (2) the underlying mechanisms of this inhibition is complex, probably reflecting a balance between the inhibitory effect of 8-MP plus UVA irradiation on mast cell-mediator release, enhancement of the vascular response to histamine, and direct photoactivation of resident mast cells.
J Allergy Clin Immunol 1991 Sep
PMID:Modulation of human cutaneous mast cell responsiveness by a single, low-dose, PUVA treatment. 189 Feb 69

To investigate the hypothesis that mast cell and neutrophil proteases stimulate airway gland secretion, we studied the effects of two mast cell proteases (tryptase and chymase) and two neutrophil enzymes (human neutrophil elastase and cathepsin G) on secretion of 35S-labeled macro-molecules from cultured bovine airway gland serous cells. Tryptase had no effect, but the other three enzymes stimulated secretion. Threshold concentrations of the enzymes (greater than or equal to 10(-10) M) were lower by two orders of magnitude than other agonists (e.g., histamine, prostaglandins, beta-adrenergic agonists). Only proteases induced maximal secretory response (greater than or equal to 80% depletion of 35S-labeled macromolecules), and these responses were greater than 10-fold larger than those of other agonists. The active catalytic sites of the enzymes are required for their secretory activities. These findings suggest a role for these enzymes in the pathogenesis of inflammatory airway diseases associated with hypersecretion, and they suggest that the use of selective site-directed inhibitors of these enzymes may provide a novel strategy for intervention in inflammatory diseases of the airways associated with hypersecretion (e.g., cystic fibrosis, chronic bronchitis).
Am Rev Respir Dis 1991 Sep
PMID:Role of mast cell and neutrophil proteases in airway secretion. 189 27

This study has examined the metabolism of arachidonic acid in the mouse bone marrow-derived mast cell (BMMC) during immunologic and nonimmunologic activation. The predominant pools of endogenous arachidonate in the mast cells were found in ethanolamine (46%), choline (39%) and inositol (14%) containing glycerolipids. Initial studies established conditions where equilibrium labelling of these major phospholipids in the BMMC could be reached. Upon challenge, arachidonate was lost from all major phospholipid classes (phosphatidylethanolamine greater than phosphatidylcholine greater than phosphatidylinositol). There was a small but significant increase in the amount of label associated with phosphatidic acid during cell activation. Arachidonate was distributed among 1-acyl, 1-alkyl and 1-alk-1-enyl-linked subclasses of PC and PE. The rank order of loss of labelled arachidonate from the major PE and PC subclasses during antigen and ionophore activation was 1-alk-enyl-2-arachidonoyl-GPE greater than 1-acyl-2-arachidonoyl-GPC greater than 1-acyl-2-arachidonoyl-GPE greater than 1-alkyl-2-arachidonoyl-GPC. Labelled products released into the supernatant fluids and free arachidonic acid within the cell accounted for the bulk of arachidonate lost from phospholipids. Labelled products in the supernatant fluids were composed of LTB4, LTC4, PGD2 and free arachidonic acid. BMMC phospholipids were also labelled for 24 hr with [3H]choline, [3H]myoinositol or [14H]ethanolamine and labelled 2-lyso phospholipids were measured after cell activation. Radioactivity in lysophospholipids from PC, PE and PI increased significantly between 30 s and 2 min after antigen activation and then declined. Taken together, these studies suggest that arachidonate is mobilized predominantly from PE and in particular 1-alk-1-enyl-2-arachidonoyl-GPE by the direct removal of arachidonate from the sn-2 position of the molecule. Most of this arachidonate is then released from cells as eicosanoids or free fatty acid.
Biochim Biophys Acta 1991 Sep 11
PMID:Arachidonic acid metabolism during antigen and ionophore activation of the mouse bone marrow derived mast cell. 189 88


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