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)

A new tetrazolium salt XTT, sodium 3'-[1-[(phenylamino)-carbonyl]-3,4-tetrazolium]-bis(4-methoxy-6- nitro)benzene-sulfonic acid hydrate, was evaluated for use in a colorimetric assay for cell viability and proliferation by normal activated T cells and several cytokine dependent cell lines. Cleavage of XTT by dehydrogenase enzymes of metabolically active cells yields a highly colored formazan product which is water soluble. This feature obviates the need for formazan crystal solubilization prior to absorbance measurements, as required when using other tetrazolium salts such as MTT. Bioreduction of XTT by all the murine cells examined was not particularly efficient, but could be potentiated by addition of electron coupling agents such as phenazine methosulfate (PMS) or menadione (MEN). Optimal concentrations of PMS or MEN were determined for the metabolism of XTT by the T cell lines HT-2 and 11.6, NFS-60 a myeloid leukemia, MC/9 a mast cell line and mitogen activated splenic T cells. When used in combination with PMS, each of these cells generated higher formazan absorbance values with XTT than were observed with MTT. Thus the use of XTT in colorimetric proliferation assays offer significant advantages over MTT, resulting from reduced assay time and sample handling, while offering equivalent sensitivity.
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PMID:An improved colorimetric assay for cell proliferation and viability utilizing the tetrazolium salt XTT. 191 29

Introduction of a reactive monohaptenic chemical into the sensitized organism will not normally result in elicitation of immediate reactions. Rather, the first products of chemical conjugation to suitable carriers in vivo are monohaptenic, conjugates which are inhibitory according to the bridging concept, stating that the initiating event for mast cell and basophil activation is a cross-linking of membrane-bound antibody by dihaptenic or oligohaptenic antigen. Simple calculations and quantitative data are presented to show that built-in inhibition is indeed a powerful barrier to any rapidly occurring allergenic manifestation which depends on the formation of divalent conjugates. If and when such a reaction does nevertheless occur, special requirements have to be invoked. One possibility is that the chemical or drug as such, i.e. without conjugation to a carrier, is an elicitor of anaphylaxis. Such compounds are known in a guinea pig passive cutaneous anaphylaxis model system, but there is evidence that they may also play a role in clinical situations. These monovalent elicitors possess in addition to the haptenic moiety an auxiliary group. The auxiliary group requirements were studied in the guinea pig passive cutaneous anaphylaxis system by using synthetic peptides with an N-terminal 2-carboxy-4,6-dinitrophenyl group as the hapten and phenylalanine and modified phenylalanine at the C-terminus as auxiliary group. The conclusions are that effective auxiliary function depends on the benzene ring and neighboring carboxyl groups in selected positions. Anaphylactogenicity is high when the haptenic and auxiliary groups can act independently, i.e. when separated by a peptide chain of considerable length. Potent anaphylactogens with close linkage of the two groups have, however, also been found. It is unlikely that the passive cutaneous anaphylaxis elicitations observed here are mediated by some form of indirect bridging of membrane-bound antibody.
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PMID:Immediate hypersensitivity to drugs and simple chemicals: the efficacy of monovalent elicitors. 257 65

A variety of modifiers of carboxypeptidase A (CPA) have been investigated in an effort to understand the structural requirements of inhibitors and activators of peptidase activity. It is proposed that an understanding of the mechanism of action of reversible activators of the enzyme may bear on the long standing question of whether the detailed mechanism of peptidase activity is different from that of esterase activity. An analog of the activator 2,2-dimethyl-2-silapentane-5-sulfonate, 5,5-dimethylhexanoate, was found to be a competitive inhibitor of the CPA-catalyzed hydrolysis of benzoylglycyl-L-phenylalanine. The modifier 4-phenyl-3-butenoate (styrylacetic acid) was determined to be an activator. The sulfonates benzene-sulfonate, p-toluenesulfonate, phenylmethanesulfonate, 2-phenylethanesulfonate, and 3-phenylpropanesulfonate were all found to be activators.
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PMID:Kinetic studies of modifier effects on the carboxypeptidase A catalyzed hydrolyses of peptides. 343 67

Skin tumors experimentally induced by dimethylbenzanthracene (DMBA) are associated with dense subepithelial accumulations of mast cells. To investigate the sequential changes of the mast cell population during carcinogenesis, and to provide a model with which to examine mast cell proliferation, the back skin of 48 Swiss Webster mice was painted with 0.5% DMBA in benzene twice weekly for 12 weeks. Control and DMBA-treated tissues were processed for histological examination. The observed pattern of tissue changes fell into four phases: a) inflammation and necrosis followed by epithelial regeneration and hyperplasia, b) development of localized regions of acanthosis, c) loss of normal organization with downgrowth of epithelial cells and formation of keratin pearls, d) appearance of well-defined nodules resembling verrucous carcinoma. Subepithelial mast cells varied greatly in number during the above sequence of changes. Dense foci of cells were seen, particularly beneath the regions of hyperplastic epithelium. Mast cells may play a role in abnormal epithelial proliferation and, further, DMBA treatment may provide a suitable model with which to examine the origin and kinetics of mast cells.
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PMID:Sequential histological changes and mast cell response in skin during chemically-induced carcinogenesis. 641 83

The widely known tree Abies pindrow (Talisapatra) (family: Pinaceae), famous for its diverse clinical uses in Ayurvedic medicines, was investigated to rationalise some of the ancient claims. The petroleum ether (PE), benzene (BE), chloroform (CE), acetone (AE) and ethanol (EE) extracts of A. pindrow leaf were found to have mast cell stabilizing action in rats. The EE, AE and BE extracts offered bronchoprotection against histamine challenge in guinea-pigs. The BE, CE and PE extracts had protective role in aspirin-induced ulcer in rats. The results suggest that while terpenoids, flavonoids, glycosides and steroids are involved in mast cell protection, terpenoids and flavonoids are brochoprotective against histamine-induced bronchospasm. The ulcer protective action of PE, BE and CE fractions of A. pindrow may be attributable to steroids contents only because though all the extracts tested positive for glycosides, the extracts EE and AE did not have any ulcer protective role.
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PMID:Pharmacological activity of Abies pindrow. 1102 38

Elaeocarpus sphaericus (Syn: E. ganitrus), in Ayurvedic Medicine commonly known as Rudraksha is known to have wide range of pharmacological activities. We reported previously the protective action of E. sphaericus in experimental bronchial asthma. The present study on rat mesenteric mast cell was undertaken to investigate the effect of E. sphaericus fruits on autacoid release. The petroleum ether (PE), benzene (BE), chloroform (CE), acetone (AE) and ethanol (EE) extracts of E. sphaericus fruits were found to have mast-cell stabilizing activity, substantiating the efficacy of E. sphaericus against bronchial asthma.
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PMID:Studies on extracts of Elaeocarpus sphaericus fruits on in vitro rat mast cells. 1118 31

Phenol (PHE) and hydroquinone (HQ) are metabolites of benzene that affect leukocytes after solvent intoxication. Hence, we investigated the effects of PHE or HQ exposure on neutrophil mobilization during an inflammatory response. Male Wistar rats received intraperitoneal injections of PHE, HQ or vehicle only and assays were performed 24 h after the last dose. Quantifications of bone marrow or circulating leukocytes showed that only HQ exposure induced neutrophilia, probably due to the accelerated mobilization from the bone marrow compartment, since reduced numbers of segmented cells in the last phase of maturation were detected there. Intravital microscopy showed that circulating leukocytes of HQ-exposed rats increased their rolling behavior and adherence to the mesenteric postcapillary venule wall in vivo. The enhanced leukocyte-endothelium interaction was not dependent on microvascular reactivity or perivascular mast cell degranulation. Instead, it was the result of neutrophil activation, demonstrated by a decrease in L-selectin and an increase in beta2 integrin expression on neutrophil membranes. This pattern of neutrophil activation may have contributed to the higher number of neutrophils in the subcutaneous inflammatory response of HQ-exposed rats after oyster glycogen injection. Taken together, our results indicate that HQ exposure alters neutrophil mobilization, which results in an exacerbated response after an injury. Although PHE is endogenously metabolized to HQ, PHE exposure only induced an increment in rolling behavior, which was not sufficient to alter the inflammatory response.
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PMID:Effect of in vivo phenol or hydroquinone exposure on events related to neutrophil delivery during an inflammatory response. 1642 81

Two phenylpropanoids, 1-allyl-3,5-dimethoxy-4-(3-methyl-but-2-enyloxy)benzene ( 4) and 4-allyl-2,6-dimethoxy-3-(3-methyl-2-butenyl)phenol ( 6), and two phytoquinoids, 4 R-(-)-illicinone-A ( 7) and 2 S,4 R-(-)-illicinone-B ( 8), isolated from plants of the ILLICIUM species significantly inhibited histamine release from rat basophilic leukemia (RBL-2H3) cells stimulated with A23187. Furthermore, these compounds caused a decline in TNF-alpha levels in culture supernatants of RBL-2H3 cells following treatment with A23187. The results indicate that these compounds might be useful as anti-inflammatory agents against mast cell-mediated inflammatory diseases.
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PMID:Anti-inflammatory activity of phenylpropanoids and phytoquinoids from Illicium species in RBL-2H3 cells. 1753 71

Hydroquinone (HQ) is naturally found in the diet, drugs, as an environmental contaminant and endogenously generated after benzene exposure. Considering that HQ alters the immune system and its several source of exposures in the environment, we hypothesized that prolonged exposure of HQ could affect the course of an immune-mediated inflammatory response. For this purpose, male Wistar rats were intraperitoneally exposed to vehicle or HQ once a day, for 22 days with a 2-day interval every 5 days. On day 10 after exposure with vehicle or HQ, animals were ovalbumin (OA)-sensitized and OA-aerosolized challenged on day 23. HQ exposure did not alter the number of circulating leukocytes but impaired allergic inflammation, evidenced by lower number of leukocytes in the bronchoalveolar lavage fluid 24h after OA-challenge. Reduced force contraction of ex vivo tracheal segments upon OA-challenge and impaired mesentery mast cell degranulation after in situ OA-challenge were also detected in tissues from HQ exposed animals. The OA-specificity on the decreased responses was corroborated by normal trachea contraction and mast cell degranulation in response to compound 48/80. In fact, lower levels of circulating OA-anaphylactic antibodies were found in HQ exposed rats, as assessed by passive cutaneous anaphylaxis assay. The reduced level of OA-anaphylactic antibody was not dependent on lower number or proliferation of lymphocytes. Nevertheless, lower expression of the co-stimulatory molecules CD6 and CD45R on OA-activated lymphocytes from HQ exposed rats indicate the interference of HQ exposure with signaling of the humoral response during allergic inflammation. Together, these data indicate specific effects of HQ exposure manifested during an immune host defense.
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PMID:In vivo hydroquinone exposure impairs allergic lung inflammation in rats. 1789 70

Benzene is a carcinogenic compound used in industrial manufacturing and a common environmental pollutant mostly derived from vehicle emissions and cigarette smoke. Benzene exposure is associated with a variety of clinical conditions ranging from hematologic diseases to chronic lung disorders. Beside its direct toxicity, benzene exerts multiple effects after being converted to reactive metabolites such as hydroquinone and benzoquinone. Mast cells and basophils are primary effector cells involved in the development of respiratory allergies such as rhinitis and bronchial asthma and they play an important role in innate immunity. Benzene and its metabolites can influence mast cell and basophil responses either directly or by interfering with other cells, such as T cells, macrophages and monocytes, which are functionally connected to mast cells and basophils. Hydroquinone and benzoquinone inhibit the release of preformed mediators, leukotriene synthesis and cytokine production in human basophils stimulated by IgE- and non IgE-mediated agonists. Furthermore, these metabolites reduce IgE-mediated degranulation of mast cells and the development of allergic lung inflammation in rats. Both in vitro and in vivo studies indicate that benzene metabolites alter biochemical and functional activities of other immunocompetent cells and may impair immune responses in the lung. These inhibitory effects of benzene metabolites are primarily mediated by interference with early transduction signals such as PI3 kinase. Together, currently available studies indicate that benzene metabolites interfere by multiple mechanisms with the role of basophils and mast cells in innate immunity and in chronic inflammation in the lung.
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PMID:Modulation of mast cell and basophil functions by benzene metabolites. 2210 54


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