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)

Sprague-Dawley rats were restrained at 4 degrees C for 2 h (stress). Tungstic acid in a single dose of 0.01, 0.1, 1, 10, 100 or 300 mg/kg (dissolved in distilled water) was administered intragastrically to animals 30 min prior to stress. Stress induced significant gastric mucosal damage, whereas tungstic acid pretreatment dose-dependently reduced lesion formation. Doses of tungstic acid of 1 mg/kg and higher significantly (P < 0.05-0.001) decreased ulcers. The mucosal mast cell counts in rats pretreated with tungstic acid were significantly higher than those of control rats. In motility experiments using oral administration of amberlite pellets, pretreatment with tungstic acid dose-dependently reduced the gastric emptying rate during a 1 h period of stress. Gastric mucosal xanthine oxidase and superoxide dismutase (SOD) activities, after pretreatment with a single dose of tungstic acid, were not altered in stressed animals. It is suggested that tungstic acid effectively antagonizes stress-induced gastric ulcers, possibly by decreasing motility and mass cell degranulation. Xanthine oxidase and SOD activities and mucous content were not changed in the gastric mucosa by the present method of tungstic acid administration.
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PMID:Tungstic acid reduction of cold-resistant stress-induced ulceration in rats. 907 17

The relationship between the changes of active oxygen metabolism and blood flow and the formation, progression, and recovery of lesions was examined in the gastric mucosa of rats treated once with compound 48/80, a mast cell degranulator. Gastric mucosal lesions appeared 0.5 hr after compound 48/80 treatment, became worst at 3 hr, and recovered fairly well at 12 hr. Increases in gastric mucosal lipid peroxide content and xanthine oxidase and myeloperoxidase activities and decreases in gastric mucosal vitamin E and hexosamine contents and Se-dependent glutathione peroxidase activity occurred with the formation and progression of gastric mucosal lesions. These changes were attenuated with the recovery of the lesion. Gastric mucosal nonprotein SH content decreased with the formation of gastric mucosal lesions, and this decreased SH content returned to near the original level with lesion progression. No changes in gastric mucosal superoxide dismutase and catalase activities occurred with the formation, progression, and recovery of gastric mucosal lesions. Gastric mucosal blood flow decreased with the formation of gastric mucosal lesions, and this decreased blood flow recovered with lesion progression. Serum serotonin concentration, an index of mast cell degranulation, increased with the formation of gastric mucosal lesions, and this increased serotonin level was attenuated with lesion progression and recovery. Pretreatment with ketotifen, a connective tissue mast cell stabilizer, prevented the formation of gastric mucosal lesions, the increases of gastric mucosal lipid peroxide content, xanthine oxidase and myeloperoxidase activities, and serum serotonin level; and the decreases of gastric mucosal nonprotein SH content, glutathione peroxidase activity, and blood flow found at 0.5 hr after compound 48/80 treatment. These results indicate that the changes of gastric mucosal active oxygen metabolism and blood flow are closely related to the formation, progression, and recovery of gastric mucosal lesions in rats with a single compound 48/80 treatment. The present results also suggest that this compound 48/80-induced gastric mucosal injury could be a kind of ischemia-reperfusion-induced injury occurring through degranulation of connective tissue mast cells.
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PMID:Relationship between changes of active oxygen metabolism and blood flow and formation, progression, and recovery of lesions is gastric mucosa of rats with a single treatment of compound 48/80, a mast cell degranulator. 920 Oct 88

Microphthalmic (mi/mi) mice are unpigmented, osteopetrotic, mast cell deficient, and exhibit diminished gastric acid secretion and natural killer cell activity. In order to assess the effect of this mutation on macrophage function, we studied superoxide (O2-) and nitric oxide (NO) production, superoxide dismutase (SOD) activity, phagocytic capacity, and tumor cell killing by peritoneal macrophages from mi/mi mice and normal (+/+) litter mates. Macrophages from mi/mi mice, upon activation with phorbol myristate acetate (PMA), generated significantly higher amounts of O2- than did macrophages from their +/+ litter mates. The phagocyte respiratory burst as assessed by nitroblue tetrazolium (NBT) reduction assay also displayed a 2-fold enhancement in mi/mi macrophages. The assay of SOD activity revealed significantly lower levels in mi/mi macrophages than in the wild type. Furthermore, in comparison with controls, macrophages from mi/mi mice demonstrated significantly higher levels of NO production and increased capacity to lyse tumor cells upon activation with lipopolysaccharide (LPS) or gamma-interferon (IFN-gamma). The mi mutation, therefore, is associated with reduced macrophage SOD activity, increased O2- and NO production, and enhanced capacity for tumor cell killing. The molecular mechanisms for these changes have not been identified.
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PMID:Macrophage function in mice with a mutation at the microphthalmia (mi) locus. 920 63

The objective of this study was to define the role of oxidants and lipid mediators in the leukocyte-endothelial cell adhesion and albumin leakage elicited in rat mesenteric venules by ischemia-reperfusion (I/R). Intravital fluorescence microscopy was used to monitor leukocyte adherence and emigration, platelet-leukocyte aggregation, mast cell degranulation, and albumin leakage after release of a 20-min arterial occlusion. I/R elicited large increases in leukocyte-endothelial cell adhesion and albumin leakage. These responses were significantly attenuated in venules treated with either superoxide dismutase, oxypurinol (an inhibitor of xanthine oxidase), lodoxamide (a mast cell stabilizer), WEB-2086 (a platelet-activating factor antagonist), or SC-41930 (a leukotriene B4-receptor antagonist) but not by U-74006F (an inhibitor of lipid peroxidation). Platelet-leukocyte aggregates and mast cell degranulation induced by I/R were also attenuated by administration of either superoxide dismutase or lodoxamide. These results support the hypothesis that oxidants produced, in part, by xanthine oxidase promote the formation (by mast cells and endothelial cells) of platelet-activating factor and leukotriene B4, which recruit and activate leukocytes in postischemic venules. The adherent and emigrated leukocytes then mediate the increased albumin extravasation observed in the postcapillary venules.
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PMID:Ischemia/reperfusion-induced microvascular dysfunction: role of oxidants and lipid mediators. 922 76

Dietary copper has long been known to be essential for cardiovascular homeostasis. However, the role of copper and cuproenzymes in the normal control of vascular physiology is not well understood. Most studies in the cardiovascular system have focused on copper deficiency-induced defects in the heart or large vessels. Recently, attention has also focused on the effects of copper deficiency in the microcirculation or the small blood vessels that control blood flow, nutrient and waste exchange, and peripheral vascular resistance. Studies in the microcirculation demonstrate that copper is important in mechanisms of macromolecular leakage, platelet-endothelial interactions and vascular smooth muscle reactivity. There is a significantly greater leakage of proteins from postcapillary venules in copper-deficient rats in response to mast cell-released histamine. This response appears to be the result of increased numbers of mast cells and thereby increased available histamine. Copper deficiency also causes an inhibition of in vivo thrombogenesis, which appears to be related to an inhibition of platelet adhesion. Subsequent studies have demonstrated that this is probably caused by a diminished concentration of the adhesion molecule von Willebrand factor. Nitric oxide (NO)-mediated arteriole vasodilation is also compromised in copper-deficient rats. This functional deficit to NO can be reversed by the addition of Cu, Zn-superoxide dismutase (SOD), suggesting that degradation of NO by superoxide anion occurs during copper deprivation. These observations demonstrate that dietary copper is necessary for several microvascular control mechanisms affecting inflammation, microhemostasis and regulation of peripheral blood flow.
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PMID:Dietary copper in the physiology of the microcirculation. 940 74

The dual radiolabeled monoclonal antibody technique was used to 1) define the magnitude and kinetics of P-selectin expression in murine small intestine exposed to ischemia-reperfusion (I/R), and 2) determine the factor(s) responsible for initiating this response. Within 10 min after release of a 20-min arterial occlusion, intestinal P-selectin expression increased two- to threefold compared with control values. Peak (4-fold) expression of P-selectin was noted at 5 h after reperfusion, returning to the control value at 24 h. The early (10-30 min) I/R-induced upregulation of P-selectin appears to reflect mobilization of a performed pool of the adhesion molecule, whereas the later (5 h) rise appears to be transcription dependent. The early increase in P-selectin expression was not inhibited by pretreatment with either oxypurinol (inhibits xanthine oxidase), diphenhydramine (H1-receptor antagonist), or MK-571 (leukotriene C4/D4 antagonist), nor was it blunted in transgenic mice expressing three times the normal level of copper-zinc superoxide dismutase or in mast cell-deficient mice. However, significant inhibition was noted after treatment with either MK-886 (5-lipoxygenase inhibitor) or a nitric oxide (NO) donor (diethylenetriamine/NO). These findings indicate that the early I/R-induced increase in intestinal P-selectin expression is mediated by a 5-lipoxygenase-dependent NO-inhibitable mechanism.
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PMID:Modulation of P-selectin expression in the postischemic intestinal microvasculature. 943 58

1. The mechanisms involved in mediating bacterial endotoxin lipopolysaccharide (LPS)-induced injury in the colon of neonatal rat pups aged 10-12 days was examined. 2. Administration of LPS (3 mg kg(-1), i.p.) caused a time-related increase in the plasma concentration of rat mast cell protease-II (RMCP-II) which was attenuated dose-dependently, by the non-selective mast cell stabilizer doxantrazole (0.05-5 mg kg(-1), i.p.). The selective connective tissue mast cell stabilizer ketotifen (5-25 mg kg(-1), i.p.) was without effect at the lower dose and had only a limited inhibitory effect at the higher dose. 3. In addition, doxantrazole (5 mg kg(-1), i.p.) inhibited mast cell degranulation in response to LPS in sections of neonatal rat colon, but ketotifen (5 mg kg(-1), i.p.) was without effect. 4. The increase in plasma RMCP-II concentration in response to LPS treatment preceded increases in tissue myeloperoxidase (MPO) activity, inducible nitric oxide synthase (iNOS) activity and tissue lipid peroxidation. These events were all attenuated by pretreatment with doxantrazole (5 mg kg(-1), i.p.), antineutrophil serum (100 microl kg(-1), i.p.), dexamethasone (2 mg kg(-1), i.p.) and the selective iNOS inhibitor, aminoguanidine (25 mg kg(-1), i.p.). 5. In addition, lipid peroxidation was inhibited by pre-administration of the antioxidant enzymes superoxide dismutase (2000 u kg(-1), i.p.) and catalase (2000 u kg(-1), i.p.), the xanthine oxidase inhibitor allopurinol (100 mg kg(-1), i.p.) and the peroxyl scavenger deferoxamine (10 mg kg(-1), i.p.), suggesting the involvement of reactive oxygen metabolites in the colonic injury. 6. These findings suggest that the sequence of events resulting in colonic damage in the neonatal rat following administration of LPS include mast cell degranulation, neutrophil infiltration, elevation in iNOS activity and subsequent lipid peroxidation.
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PMID:Role of mast cells, neutrophils and nitric oxide in endotoxin-induced damage to the neonatal rat colon. 948 51

This study investigated whether short-term exposure to Escherichia coli lipopolysaccharide (LPS) elicits vasomotor dysfunction in skeletal muscle in vivo and, if so, whether perivascular mast cell proteases partly modulate this response. With intravital microscopy, we found that suffusion of E. coli LPS on the in situ hamster spinotrapezius muscle for 60 min elicits immediate vasoconstriction followed by vasodilation. Vasoconstriction is abrogated by SK&F 108566, a selective, nonpeptide angiotensin II (AT II) subtype 1 receptor antagonist, chymostatin and soybean trypsin inhibitor. These compounds also attenuate E. coli LPS-induced vasodilation. By contrast, superoxide dismutase, catalase and indomethacin attenuate only E. coli LPS-induced vasodilation. Endothelin receptor antagonists, lisinopril, leupeptin, Bestatin and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid are ineffective. Histochemical analysis of the spinotrapezius muscle reveals abundant perivascular mast cells with chymostatin-inhibitable chymase-like activity. Pretreatment of hamsters with compound 48/80 for 4 days curtails E. coli LPS-induced vasoconstriction and converts vasodilation to vasoconstriction. On balance, these data indicate that E. coli LPS stimulates perivascular mast cells in the in situ hamster spinotrapezius muscle to release an AT II-producing chymase-like protease(s). AT II thus produced elicits local vasoconstriction and elaborates reactive oxygen species which, in turn, generate vasodilator prostaglandins.
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PMID:Mast cell chymase-like protease(s) modulates Escherichia coli lipopolysaccharide-induced vasomotor dysfunction in skeletal muscle in vivo. 949 78

Local inhibition of nitric oxide (NO) synthesis with L-arginine analogs such as NG-nitro-L-arginine methyl ester (L-NAME) decreased red blood cell velocity (VRBC) in capillaries and increased leukocyte adhesion in postcapillary venules in rat skeletal muscle. The goal of the present study was to determine the mechanism of this response to L-NAME. Using intravital videomicroscopy, we examined blood flow in the surface microvasculature of rat extensor digitorum longus muscle. L-NAME (30 mM in the pipette) locally applied to capillaries (300 microns from feeding arteriole) reduced VRBC [control VRBC = 244 +/- 53 (SE) microns/s; delta VRBC = -52 +/- 8%] and increased leukocyte adhesion (from 0.2 +/- 0.01 to 1.3 +/- 0.3 cells/100 microns) in control animals. Systemic pretreatment with fucoidan (selectin binder), superoxide dismutase and catalase (extracellular antioxidants), dimethylthiourea (intracellular antioxidant), or ketotifen (mast cell stabilizer) did not alter this response. Pretreatment with CL26, an anti-CD18 antibody, abolished the L-NAME response. Our results suggest that L-NAME increased leukocyte-endothelial interactions via an effect on CD11/CD18 or its ligand, intercellular adhesion molecule.
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PMID:Local L-NAME decreases blood flow and increases leukocyte adhesion via CD18. 957 30

It has been shown that hypercholesterolemia (HCh) exaggerates the microvascular dysfunction that is elicited by ischemia and reperfusion (I/R). The objective of this study was to determine whether oxidants contribute to the exaggerated inflammatory responses and enhanced albumin leakage observed in HCh rat mesenteric venules exposed to I/R (10 minutes of ischemia and 30 minutes of reperfusion). Intravital videomicroscopy was used to quantify the number of adherent and emigrated leukocytes, albumin extravasation, platelet-leukocyte aggregation in postcapillary venules, and the degranulation of adjacent mast cells. Oxidation of the fluorochrome dihydrorhodamine 123 (DHR) was used to monitor oxidant production by venular endothelium. I/R was shown to elicit an increased DHR oxidation in venules of both control and HCh rats, with the latter group exhibiting a significantly larger response. Treatment with either oxypurinol or superoxide dismutase largely prevented the leukocyte recruitment, platelet-leukocyte aggregation, mast cell degranulation, and enhanced DHR oxidation elicited by I/R in HCh rats. The enhanced albumin leakage was reduced by superoxide dismutase but not by oxypurinol. These results indicate that HCh amplifies the oxidant stress elicited by I/R and that interventions that blunt the oxidant stress effectively attenuate the leukocyte, platelet, and mast cell activation that result from I/R.
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PMID:Hypercholesterolemia enhances oxidant production in mesenteric venules exposed to Ischemia/Reperfusion. 976 30


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