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Despite high bacterial colonization and frequent allergen contact, acute inflammatory and allergic reactions are rarely seen in the oral mucosa. Therefore we assert that immune tolerance predominates at this site and antigen presenting cells, such as dendritic cells and different T cell subtypes, serve as key players in oral mucosal tolerance induction. In this article we describe the mechanisms that lead to tolerance induced in the oral mucosa and how they differ from tolerance induced in the lower gastrointestinal tract. Furthermore we discuss ways in which novel nonparenteral approaches for immune intervention, such as allergen-specific immunotherapy applied by way of the sublingual route, might be improved to target the tolerogenic properties of the sophisticated oral mucosal immune network. 相似文献
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When the differential fluorescence emission at 515 nm of receptor-rich membrane fragments from Torpedo marmorata labelled with quinacrine is followed by energy transfer, addition of a high concentration of an agonist such as 0.4 mm-carbamylcholine or 0.4 mm-phenyltrimethylammonium causes a fast (unresolved) increase of fluorescence intensity followed by a slow (minute range) decrease, which leads to a final stable level. On the other hand, a stepwise addition of agonist at low concentrations gives only a slow fluorescence increase. Antagonists, such as flaxedil and d-tubocurarine, at all the concentrations tested, bring about exclusively slow fluorescence increases. Decamethonium at 0.4 mm gives no slow reaction but only a fast (unresolved) increase without transient overshoot.Addition of a local anaesthetic reduces the amplitude of the fluorescence response to carbamylcholine. The α-toxin from Naja nigricollis does not cause any change of fluorescence intensity but blocks the effect of the cholinergic agonists and antagonists.Dissolution of the membrane fragments by a non-ionic detergent abolishes the fast transient reaction triggered by the agonists but preserves the slow ones observed in the presence of agonists or antagonists. The data are interpreted in terms of a three-state model, a revised version of the model of Katz & Thesleff (1957): the fast transient reaction brought about by the agonists being assigned to the “activation” of the receptor-ionophore complex and the slow one to its “desensitization”. 相似文献
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Rachel Nadif Margaret Mintz Anne Jedlicka Jean-Pierre Bertrand Steven R. Kleeberger Francine Kauffmann 《Free radical research》2013,47(12):1345-1350
We tested the hypotheses that catalase activity is modified by CAT single nucleotide polymorphisms (SNPs) (-262;-844), and by their interactions with oxidant exposures (coal dusts, smoking), lymphotoxin alpha (LTA, NcoI) and tumor necrosis factor (TNF, -308) in 196 miners. Erythrocyte catalase, superoxide dismutase, and glutathione peroxidase activities were measured. The CAT -262 SNP was related to lower catalase activity (104, 87 and 72 k/g hemoglobin for CC, CT and TT, respectively, p < 0.0001). Regardless of CAT SNPs, the LTA NcoI but not the TNF-308 SNP was associated with catalase activity (p = 0.04 and p = 0.8). CAT -262 T carriers were less frequent in highly exposed miners (OR = 0.39 [0.20–0.78], p = 0.007). In CAT -262 T carriers only, catalase activity decreased with high dust exposure (p = 0.01). Haplotype analyses (combined CAT SNPs) confirm these results. Results show that CAT -262 and LTA NcoI SNPs, and interaction with coal dust exposure, influenced catalase activity. 相似文献
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Jeremie Boyer Vania Bernardes-Genisson Vincent Farines Jean-Pierre Souchard Francoise Nepveu 《Free radical research》2013,47(5):459-471
A series of 2-alkyl and 2-aryl substituted-3H-indol-3-one-1-oxides was prepared and evaluated for its radical trapping properties. Spin trapping and electron paramagnetic resonance experiments demonstrate the ability of these indolone-1-oxides to trap hetero- and carbon-centered radicals. The most stable spin adducts (lifetime of several hours) are obtained with 2-alkyl substituted nitrones, the 2-ethyl-5,6-dioxolo-3H-indolone-1-oxide, 5e and the 2-secbutyl-3H-indolone-1-oxide, 5f. These two nitrones are also sensitive to redox reactions in solution. Therefore this indolone-1-oxide series lacking a β-hydrogen atom gives rise to highly stable adducts with free radicals. 相似文献
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Gilles Gosselin Christophe Mathé Marie-Christine Bergogne Anne-Marie Aubertin Andre Kirn Jean-Pierre Sommadossi 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):611-617
Abstract Several L-enantiomers of nucleoside analogues were stereospecifically synthesized by a multi-step reaction from L-xylose and their antiviral properties were examined in vitro. Two of them, namely β-L-2′,3,′-dideoxycytidine (β-L-ddC) and its 5-fluoro derivative (β-L-FddC) were found to have potent anti-human immunodeficiency virus (HIV) and significant anti-hepatitis B virus (HBV) activities in cell cultures. 相似文献
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Patrice Vincent Jean-Pierre Beaucourt Louis Pichat Jan Balzarini Erik De Clercq 《Nucleosides, nucleotides & nucleic acids》2013,32(4):447-462
Abstract (E) 5-Alkenyl 2′-deoxyuridines were synthesized with moderate to high yields by the palladium catalyzed coupling of alkenyl-zirconium reagents with 0–3′, 5′-his (trimethylsilyl) deoxyuridine in T H F. Some of these 5-alkenyl-dUrd analogues, i.e. the 1-decenyl (5g) and 2- (1-hydroxycyclopentyl) ethenyl (5f) derivatives, inhibited murine L1210 cell growth at a concentration of about 4 μg/ml, whereas the 5-chloro-1-pentenyl (5c), 5-cyano-1-pentenyl (5d), 5-hexyn-1-enyl (5e) and 2-(1-hydroxycyclopentyl) ethenyl (5f) were inhibitory towards herpes simplex and vaccinia virus within the concentration range of 2–60 μg/ml. However, none of the newly synthesized 5-alkenyl-dUrd analogues proved selective in its antiviral action. 相似文献