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The intracellular pathway of polymeric immunoglobulin receptor (pIgR) is governed by multiple signals that lead to constitutive transcytosis. In addition, in transfected polarized MDCK cells, polymeric immunoglobulin A (pIgA) binding stimulates rabbit pIgR-transcytosis, owing to phospholipase-C gamma 1 activation and increase of intracellular calcium. Transcytosis of rat pIgR across hepatocytes is similarly accelerated by pIgA injection. In contrast we show here that human Madrin-Darby Canine Kidney (pIgR)-transcytosis, in human Calu-3 and human pIgR-transfected MDCK cells, is not promoted by pIgA, as monitored by a continuous apical release of its secreted ectodomain. However, the incubation of cells expressing human or rabbit pIgR with pIgA induces a comparable IP3 production, and pIgR-transcytosis of either species is accelerated by the protein kinase C (PKC)-activator phorbol myristate acetate. Without pIgA, mimicking phospholipase-C activation by combining low concentrations of phorbol myristate acetate with ionomycin, or high concentrations of ionomycin alone, stimulates the rabbit, but not the human, pIgR transcytosis. These data suggest that the species difference in pIgA-induced pIgR-transcytosis does not stem from the defective production of second messengers, but from a different sensitivity of pIgR to intracellular calcium. Our results outline the danger of extrapolating to humans the abundant data obtained from mucosal vaccination of laboratory animals. 相似文献
2.
Lack of SC/pIgR-mediated epithelial transport of a human polymeric IgA devoid of J chain: in vitro and in vivo studies. 总被引:2,自引:0,他引:2 下载免费PDF全文
Three human polymeric IgA (pIgA) myeloma proteins of tetrameric size were compared for their J-chain content, their in vitro secretory component (SC)-binding ability, and their capacity to be transcytosed by polymeric immunoglobulin receptor (pIgR)-expressing epithelial cells in vitro and rat hepatocytes in vivo. One of the three pIgA preparations, pIgA-L, was shown to lack J chain and was unable to combine with purified free human and rat SC, whereas pIgA-G and pIgA-C contained J chain and combined readily with SC. Furthermore, pIgA-L was not transferred into rat bile after intravenous injection, and was hardly transported apically by polarized Madin-Darbey canine kidney cell monolayers expressing the human pIgR, whereas pIgA-G and pIgA-C were efficiently transported in both test systems. Together with our recent demonstration that antibodies to human J chain block the SC/pIgR-mediated epithelial transport of pIgA, these data unanimously confirm the proposed key role of J chain in the epithelial transport of polymeric immunoglobulins into exocrine secretions. 相似文献
3.
Jean-Pierre Vaerman Agnes E. Langendries Didier A. Giffroy Charlotte S. Kaetzel Carol M. Tamer Fiani Itaru Moro Per Brandtzaeg Kunihiko Kobayashi 《European journal of immunology》1998,28(1):171-182
To emphasize the requirement for a J chain in native polymeric immunoglobulins for their selective transport into exocrine secretions, IgG, purified from two different antisera specific for the human J chain, was shown to: (i) bind in vitro to human polymeric IgA (pIgA) by density gradient ultracentrifugation; (ii) inhibit binding in vitro of rat secretory component to human pIgA; (iii) inhibit hepatic transport of human pIgA into rat bile in vivo; and (iv) inhibit apical transcytosis of pIgA in vitro by polarized human polymeric immunoglobulin receptor (pIgR)-expressing Madin-Darby canine kidney cells. Inhibition of biliary transport increased with the molar ratio of anti-J chain antibodies against pIgA and their incubation time. Anti-J chain F(ab ′ )2 and Fab fragments also inhibited biliary transport, excluding a role for phagocytic clearance or excessive size of the immune complexes. Anti-human-Fcα Fab, bound to human pIgA in complexes of larger size than those with anti-J chain Fab, did not inhibit biliary transport of human pIgA. Propionic acid-denatured human pIgA, although containing J chains, was very poorly transported into rat bile. Altogether, our data strongly support, now also by in vivo experiments, the crucial role of the J chain of native pIgA in its selective pIgR-mediated transport into secretions, as suggested long ago by in vitro data only. Recent data on J chain-knockout mice, with low IgA levels in bile and feces, cannot explain the role of the J chain in contributing to the secretory component/pIgR-binding site of normal pIgA, but otherwise agree with our study. 相似文献
4.
This paper's primary objective is to analyse the physiological (cortisol) and behavioral responses of military working dogs (MWD). Dogs (N=27) were submitted twice to environmental challenges (challenge 1 and 2, 20 days in-between) composed of social (training), visual (mobile toy car) and auditory (air blast) stimuli. Cortisol levels decreased back to the baseline after the second challenge. The behavioral observations showed that these MWD were more active, and presented less stereotypic behaviors (pacing, manipulation of the environment) during both visual challenges, whereas half low posture was observed during the first but not during the second visual challenge. The present study shows that this group of MWD still has an adaptation capacity to an environmental challenge (return to baseline of the cortisol levels, a higher posture during the second than at the first challenge). These results are encouraging and indicate that the dogs might have a diminished welfare (i.e. stereotypic behaviors), but are not chronically stressed. 相似文献
5.
Giffroy D Mazy C Duchêne M 《Pharmeuropa bio / the Biological Standardisation Programme, EDQM》2006,2006(1):7-14
The discontinuation of the Auszyme kit used by vaccine manufacturers and national control laboratories to determine the Hepatitis B surface antigen (HBsAg) content of hepatitis B vaccines has led GlaxoSmithKline (GSK) to develop an alternative inhibition ELISA method. Validation of this ELISA was performed according to The International Conference of Harmonization and reproducibility was assessed in a feasibility study with four Official Medicines Control Laboratories (OMCLs). The dose response curve demonstrated linearity (R2>0.99) in the range of 60-360 ng/ml HBsAg. The repeatability (CV<7%), intermediate precision (CV<10%) and accuracy (91-113% recovery) were similar to the Auszyme method. The commercial antibodies used in the assay were shown to contain antibodies that bind to a protective epitope of HBsAg and the specificity of the method for HBsAg was demonstrated. There was a good concordance with the Auszyme method, although the ELISA yielded higher results (25.3 vs. 24.4 micro.g/ml for Engerix-B (n=64), 28.9 vs. 27.0 micro.g/ml for Twinrix (n= 69) and 25.5 vs. 21.6 micro.g/ml for Infanrix penta (n=62)). The method was successfully transferred to the four OMCLs. It has been demonstrated that the ELISA is suitable for its intended purpose with hepatitis B-containing vaccines from GSK and thus could be used for these vaccines by national control laboratories and authorities. Further validation studies should focus on the use of this ELISA with vaccines from other manufacturers. 相似文献
6.
Lefebvre D Lips D Giffroy JM 《Revue scientifique et technique (International Office of Epizootics)》2007,26(3):619-628
The European Convention for the Protection of Pet Animals was opened for signature in Strasbourg on 13 November 1987 and entered into force on 1 May 1992. This Convention states that: 'Surgical operations for the purpose of modifying the appearance of a pet animal or for other non-curative purposes shall be prohibited and, in particular: the docking of tails'. At present, 15 of the 27 States in the European Union have ratified this Convention (with or without reserving their position on tail docking) and have prohibited cosmetic surgical operations. In addition, four European States have prohibited these operations, even though they did not ratify the Convention. These policy positions agree with both the current knowledge on tail amputations in dogs and the opinions of official veterinary associations in Europe and North America. 相似文献
7.
Xavier Giffroy Nathalie Maes Adelin Albert Pierre Maquet Jean-Michel Crielaard Dominique Dive 《Acta neurologica Belgica》2017,117(1):53-59
The clinical variability and complexity of multiple sclerosis (MS) challenges the individual clinical course prognostication. This study aimed to find out whether multimodal evoked potentials (EP) correlate with the motor components of multiple sclerosis functional composite (MSFCm) and predict clinically relevant motor functional deterioration. One hundred MS patients were assessed at baseline (T 0) and about 7.5 years later (T 1), with visual, somatosensory and motor EP and rated on the Expanded Disability Status Scale (EDSS) and the MSFCm, including the 9 Hole Peg Test and the Timed 25 Foot Walk (T25FW). The Spearman correlation coefficient (r S) was used to evaluate the cross-sectional and longitudinal relationship between EP Z scores and clinical findings. The predictive value of baseline electrophysiological data for clinical worsening (EDSS, 9-HPT, T25FW, MSFCm) during follow-up was assessed by logistic regression analysis. Unlike longitudinal correlations, cross-sectional correlations between EP Z scores and clinical outcomes were all significant and ranged between 0.22 and 0.67 (p < 0.05). The global EP Z score was systematically predictive of EDSS and MSFCm worsening over time (all p < 0.05). EP latency was a better predictor than amplitude, although weaker than latency and amplitude aggregation in the global EP Z score. The study demonstrates that EP numerical scores can be used for motor function monitoring and outcome prediction in patients with MS. 相似文献
8.
In vivo stimulation of polymeric Ig receptor transcytosis by circulating polymeric IgA in rat liver 总被引:3,自引:0,他引:3
Giffroy D; Langendries A; Maurice M; Daniel F; Lardeux B; Courtoy PJ; Vaerman JP 《International immunology》1998,10(3):347-354
Binding of human polymeric IgA ligand to its epithelial cell polymeric Ig
receptor, pIgR, has been shown to stimulate pIgR apical transcytosis in an
in vitro system, based on polarized confluent MDCK cells expressing rabbit
pIgR. The present study aimed at testing whether such a stimulation also
occurs in vivo. Transcytosis of pIgR was monitored by rat liver output of
total secretory component (SC) into bile, measured by radial
immunodiffusion as the sum of free SC and pIgA-bound SC. Whereas in the
perfused rat liver system addition of pIgA to the perfusate showed no
effect, i.v. injection of human and rat pIgA, but not of monomeric IgA nor
PBS, in living rats significantly increased total bile SC output for more
than 1 h. Furthermore, depletion of the normal pIgA level circulating in
the liver before injecting more pIgA was not required to show the
stimulation. Our data thus strongly suggest that stimulation of liver pIgR
transcytosis by pIgA ligand binding is physiologically relevant, helping to
quickly adjust pIgA transport into bile to increase circulating pIgA
levels, without need for increased SC/pIgR synthesis.
相似文献
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