Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhalation of aerosols of ovalbumin in sensitized guinea pigs produced a marked, bronchoalveolar eosinophilia 24 hr after challenge. The lung eosinophilia was not prevented by the cyclooxygenase inhibitors, indomethacin or PAF antagonists (WEB-2086 and L-652731) but was inhibited by methylprednisolone, the 5-LO inhibitor, U-66858 and a series of structural analogs of LTB4, U-75302, U-77692, U-75485 and U-78489. The effectiveness of LTB4 antagonists but not PAF antagonists in vivo was consistent with in vitro studies in which LTB4 was shown to be far more chemotactic than PAF for guinea pig eosinophils. LTB4 elicited maximal directional migration of guinea pig eosinophils at concentrations from 10(-7) M to 10(-9) M while PAF showed no effect over the same concentration range. The structural analogs of LTB4 were shown to inhibit LTB4 induced chemotaxis of guinea pig eosinophils and produced a dose-related inhibition of binding of LTB4 to guinea pig eosinophil membranes. To add further proof to the hypothesis that LTB4 contributed to the antigen-induced lung eosinophilia we attempted to measure LTB4 release into BAL fluid immediately after and at various time points up to 24 hr after antigen inhalation. However, using a sensitive radioimmunoassay (detection limit 10 pg/ml) very low levels of LTB4 (24.9-67.9 pg/ml) or its metabolite, 20-OH LTB4 (24.9-98.2 pg/ml) were detected in BAL fluid and these levels did not increase significantly following antigen provocation. Inhalation of LTB4 aerosols in unsensitized Brown-Norway rats or inhalation of aerosols of ovalbumin in sensitized Brown-Norway rats also produced a marked "late-phase" eosinophil-rich influx of inflammatory cells into the lungs. The lung eosinophilia in the rat was prevented by two structurally unrelated leukotriene B4 (LTB4) antagonists, U-75302 and Ly255283. These data implicate LTB4 as a mediator of allergen-induced bronchopulmonary eosinophilia. Leukotriene B4 antagonists may provide leads for the development of compounds which inhibit the chronic airway inflammation associated with asthma in man.
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PMID:Contribution of leukotriene B4 to airway inflammation and the effect of antagonists. 165 82

Exposure of normal guinea pigs to an aerosol of PAF induced an increase in airway responsiveness to i.v. histamine, 24 h and 48 h post challenge compared to animals that received BSA alone. There was no significant alteration in airway responsiveness 1 h, 4 h or 72 h after PAF challenge. Exposure of actively sensitised guinea pigs to an aerosol of ovalbumin induced airway hyperresponsiveness to i.v. histamine, 24 h post challenge. PAF induced a selective increase in the percentage of eosinophils in bronchoalveolar lavage fluid 24 h after challenge, that persisted for at least 72 h post challenge. No significant increase in eosinophils was noted 1-4 h after PAF exposure. Antigen challenge of actively sensitised guinea pigs induced a significant increase in the percentage of eosinophils recovered in BAL fluid 24 h post challenge. Pretreatment of both normal and sensitised guinea pigs with the selective PAF antagonist WEB 2170 significantly inhibited both airway hyperresponsiveness and airway eosinophilia 24 h post challenge with aerosol PAF or allergen. These results further support the suggestion that PAF may play a central role in allergen induced eosinophil infiltration and airway hyperresponsiveness in the guinea pig.
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PMID:The effect of the selective PAF antagonist WEB 2170 on PAF and antigen induced airway hyperresponsiveness and eosinophil infiltration. 189 85

The authors studied the inflammation's factors of the lung in six asthmatic children in BAL liquid. Were monitored either the cells either the inflammation's mediators as PCF--albumin--PGE2--PG1 alpha--Tx beta 2--PAF--LT beta 4 and the interleukines IL1 alpha--IL-1 beta--IL-6--IL-8. In the BAL liquid was observed the macrophagic non epiteliomorphic and lymphocytic preminence. The mediators of inflammation were all increased in particular IL-1 beta--IL-6--IL-8. The cultural exams were negatives in 80% of children.
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PMID:[The correlations between chemical mediators and interleukins in the bronchoalveolar lavage fluid in 6 asthmatic children]. 832 21

Cysteinyl leukotrienes are important mediators of asthma, and inhibition of their effects may represent a potential breakthrough in the therapy of allergic rhinitis and asthma. Strategies for inhibition of cysteinyl leukotriene receptors and inhibition of 5-lipoxygenase activity. The leukotrienes antagonists, with particular reference to asthma and allergic rhinitis, is reviewed in this paper. In studies in asthmatic patients, these compounds can inhibit bronchoconstriction in response to exercise, aspirin and allergen. Results from clinical studies using receptor antagonists, such as LY-171883, SK&F-104353, ICI-204219, ONO-1078, MK-751, MK-0679, demonstrate beneficial effects, with improvement in symptoms and forced expiratory volume in one second (FEV1), and a reduction in the use of beta 2-adrenergic relief medication. NZ-107 was studied for its effect on airway inflammation caused by intratracheal injection of LTB4 or IL-5, or by inhalation of PAF, and by cell activation. Analysis of the BAL fluid revealed that both induced eosinophilia and neutrophilia were suppressed. Surprisingly, although PAF and superoxide generation were inhibited in macrophages and eosinophils, NZ-107 had no effect on neutrophil activation. U-75302 was studied in guinea pigs and inhibited LTB4 induced chemotaxis of eosinophils in vitro and antigen-induced lung eosinophilia in vivo. Further studies are needed to clarify the exact mechanism by which these compounds provide beneficial effects.
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PMID:Leukotrienes and their antagonists in allergic disorders. 915 Aug 42

The lipid mediator PAF plays an important role in the phagocytosis of particles, including bacteria, and consequent production of pro-inflammatory cytokines, such as TNF-alpha and IL-8. Using a PAF receptor antagonist (UK-74,505) and PAF receptor knock-out mice, we have investigated the relevance of PAF for the inflammatory changes and lethality after pulmonary infection with the gram-negative bacteria Klebsiella pneumoniae in mice. At an inoculum of 3 x 10(6) bacteria, there was marked pulmonary (bronchoalveolar lavage and lung) neutrophilia that started early (2.5 h after infection) and peaked at 48 h. All animals were dead by day 4 of infection. The chemokine KC and the pro-inflammatory cytokine TNF-alpha increased rapidly and persisted for 48 h in the lungs. Pretreatment with UK-74,505 (30 mg kg(-1) per day, p.o.) had no significant effects on the number of infiltrating neutrophils in BAL fluid or lung tissue, as assessed by histology and measuring myeloperoxidase, or on the concentrations of KC. In contrast, concentrations of TNF-alpha and the number of bacteria inside neutrophils were significantly diminished. In order to support a role for the PAF during K. pneumoniae infection, experiments were also carried out in PAFR-deficient mice. In the latter animals, lethality occurred earlier than in wild-type controls. This was associated with greater number of bacteria in lung tissue and diminished percentage of neutrophils containing bacteria in their cytoplasm. Our results suggest that PAF, acting on its receptor, plays a protective role during infection with K. pneumoniae in mice.
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PMID:Role of the platelet-activating factor (PAF) receptor during pulmonary infection with gram negative bacteria. 1238 75

Eosinophil degranulation has been implicated in inflammatory processes associated with allergic asthma. Rab27a, a Rab-related GTPase, is a regulatory intracellular signaling molecule expressed in human eosinophils. We postulated that Rab27a regulates eosinophil degranulation. We investigated the role of Rab27a in eosinophil degranulation within the context of airway inflammation. Rab27a expression and localization in eosinophils were investigated by using subcellular fractionation combined with Western blot analysis, and the results were confirmed by immunofluorescence analysis of Rab27a and the granule membrane marker CD63. To determine the function of eosinophil Rab27a, we used Ashen mice, a strain of Rab27a-deficient animals. Ashen eosinophils were tested for degranulation in response to PAF and calcium ionophore by measuring released EPX activity. Airway EPX release was also determined by intratracheal injection of eosinophils into mice lacking EPX. Rab27a immunoreactivity colocalized with eosinophil crystalloid granules, as determined by subcellular fractionation and immunofluorescence analysis. PAF induced eosinophil degranulation in correlation with redistribution of Rab27a(+) structures, some of which colocalized with CD63(+) crystalloid granules at the cell membrane. Eosinophils from mice had significantly reduced EPX release compared with normal WT eosinophils, both in vitro and in vivo. In mouse models, Ashen mice demonstrated reduced EPX release in BAL fluid. These findings suggest that Rab27a has a key role in eosinophil degranulation. Furthermore, these findings have implications for Rab27a-dependent eosinophil degranulation in airway inflammation.
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PMID:An essential role for Rab27a GTPase in eosinophil exocytosis. 2398 49