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991.
992.
Richard Pfeiffer, working with Robert Koch in Berlin, intellectually and experimentally conceived the concept of endotoxin as a heat-stable bacterial poison responsible for the pathophysiological consequences of certain infectious diseases. Pfeiffer's definition of endotoxin included the inability to evoke neutralizing antibodies against this bacterial toxin. Alexandre Besredka, Ilya (Elie) Metchnikoff's successor at the Institut Pasteur in Paris, was the first to demonstrate that, in fact, antibodies could be engendered which were capable of suppressing the poisonous effects of endotoxin. Endotoxin and anti-endotoxin antibodies have since then fascinated researchers of many disciplines and continue to do so, particularly in the fields of diagnosis, prevention, and therapy of severe Gram-negative infections. 相似文献
993.
HLA-DR-mediated apoptosis susceptibility discriminates differentiation stages of dendritic/monocytic APC 总被引:3,自引:0,他引:3
Bertho N Drénou B Laupeze B Berre CL Amiot L Grosset JM Fardel O Charron D Mooney N Fauchet R 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(5):2379-2385
Professional APC are characterized by their ability to present peptide via HLA class II in the presence of costimulatory molecules (CD40, CD80, and CD86). The efficiency of Ag presentation can be classed as follows: mature dendritic cells (DC) are most efficient, immature DC and macrophages are intermediate, and monocytes are considered poor APC. There is a large body of evidence demonstrating that HLA-DR transmits signals in the APC. In this study, we have addressed the question of the outcome of HLA-DR signals on APC of the monocyte/DC lineages throughout their differentiation from immature to mature APC. DC were generated from both monocytes and CD34+ cells of the same individual, macrophages were differentiated from monocytes. Immunophenotypical analysis clearly distinguished these populations. HLA-DR-mediated signals led to marked apoptosis in mature DC of either CD34 or monocytic origin. Significantly less apoptosis was observed in immature DC of either origin. Nonetheless, even immature DC were more susceptible to HLA-DR-mediated apoptosis than macrophages, whereas monocytes were resistant to HLA-DR-mediated apoptosis. The mechanism of HLA-DR-mediated apoptosis was independent of caspase activation. Taken together, these data lead to the notion that signals generated via HLA-DR lead to the demise of mature professional APC, thereby providing a means of limiting the immune response. 相似文献
994.
MUC1-specific immune responses in human MUC1 transgenic mice immunized with various human MUC1 vaccines 总被引:12,自引:0,他引:12
Acres B Apostolopoulos V Balloul JM Wreschner D Xing PX Ali-Hadji D Bizouarne N Kieny MP McKenzie IF 《Cancer immunology, immunotherapy : CII》2000,48(10):588-594
Analyses of MUC1-specific cytotoxic T cell precursor (CTLp) frequencies were performed in mice immunized with three different
MUC1 vaccine immunotherapeutic agents. Mice were immunized with either a fusion protein comprising MUC1 and glutathione S-transferase (MUC1-GST), MUC1-GST fusion protein coupled to mannan (MFP) or with a recombinant vaccinia virus expressing both
MUC1 and interleukin-2. Mouse strain variations in immune responsiveness have been observed with these vaccines. We have constructed
mice transgenic for the human MUC1 gene to study MUC1-specific immune responses and the risk of auto-immunity following MUC1 immunization. Transgenic mice immunized
with MUC1 were observed to be partially tolerant in that the MUC1-specific antibody response is lower than that observed in
syngeneic but non-transgenic mice. However, a significant MUC1-specific CTLp response to all three vaccines was observed,
indicating the ability to overcome T cell, but to a lesser extent B cell, tolerance to MUC1 in these mice. Histological analysis
indicates no evidence of auto-immunity to the cells expressing the human MUC1 molecule. These results suggest that it is possible
to generate an immune response to a cancer-related antigen without damage to normal tissues expressing the antigen.
Received: 7 July 1999 / Accepted: 26 August 1999 相似文献
995.
Mouzat K Prod'homme M Volle DH Sion B Déchelotte P Gauthier K Vanacker JM Lobaccaro JM 《The Journal of biological chemistry》2007,282(7):4693-4701
The uterus is an organ where lipid distribution plays a critical role for its function. Here we show that nuclear receptor for oxysterols LXRbeta prevents accumulation of cholesteryl esters in mouse myometrium by controlling expression of genes involved in cholesterol efflux and storage (abca1 and abcg1). Upon treatment with an LXR agonist that mimics activation by oxysterols, expression of these target genes was increased in wild-type mice, whereas under basal conditions, lxralpha;beta(-/-) mice exhibited a marked decrease in abcg1 accumulation. This change resulted in a phenotype of cholesteryl ester accumulation. Besides, a defect of contractile activity induced by oxytocin or PGF2alpha was observed in mice lacking LXRbeta. These results imply that LXRbeta provides a safety valve to limit cholesteryl ester levels as a basal protective mechanism in the uterus against cholesterol accumulation and is necessary for a correct induction of contractions. 相似文献
996.
Tai SL Daran-Lapujade P Luttik MA Walsh MC Diderich JA Krijger GC van Gulik WM Pronk JT Daran JM 《The Journal of biological chemistry》2007,282(14):10243-10251
997.
Simon S Fontaine JM Martin JL Sun X Hoppe AD Welsh MJ Benndorf R Vicart P 《The Journal of biological chemistry》2007,282(47):34276-34287
Three mutations (R120G, Q151X, and 464delCT) in the small heat shock protein alphaB-crystallin cause inherited myofibrillar myopathy. In an effort to elucidate the molecular basis for the associated myopathy, we have determined the following for these mutant alphaB-crystallin proteins: (i) the formation of aggregates in transfected cells; (ii) the partition into different subcellular fractions; (iii) the phosphorylation status; and (iv) the ability to interact with themselves, with wild-typealphaB-crystallin, and with other small heat shock proteins that are abundant in muscles. We found that all three alphaB-crystallin mutants have an increased tendency to form cytoplasmic aggregates in transfected cells and significantly increased levels of phosphorylation when compared with the wild-type protein. Although wild-type alphaB-crystallin partitioned essentially into the cytosol and membranes/organelles fractions, mutant alphaB-crystallin proteins partitioned additionally into the nuclear and cytoskeletal fractions. By using various protein interaction assays, including quantitative fluorescence resonance energy transfer measurements in live cells, we found abnormal interactions of the various alphaB-crystallin mutants with wild-type alphaB-crystallin, with themselves, and with the other small heat shock proteins Hsp20, Hsp22, and possibly with Hsp27. The collected data suggest that eachalphaB-crystallin mutant has a unique pattern of abnormal interaction properties. These distinct properties of the alphaB-crystallin mutants identified are likely to contribute to a better understanding of the gradual manifestation and clinical heterogeneity of the associated myopathy in patients. 相似文献
998.
999.
1000.
Fernández-Montalván A Bouwmeester T Joberty G Mader R Mahnke M Pierrat B Schlaeppi JM Worpenberg S Gerhartz B 《The FEBS journal》2007,274(16):4256-4270
Ubiquitin specific protease 7 (USP7) belongs to the family of deubiquitinating enzymes. Among other functions, USP7 is involved in the regulation of stress response pathways, epigenetic silencing and the progress of infections by DNA viruses. USP7 is a 130-kDa protein with a cysteine peptidase core, N- and C-terminal domains required for protein-protein interactions. In the present study, recombinant USP7 full length, along with several variants corresponding to domain deletions, were expressed in different hosts in order to analyze post-translational modifications, oligomerization state, enzymatic properties and subcellular localization patterns of the enzyme. USP7 is phosphorylated at S18 and S963, and ubiquitinated at K869 in mammalian cells. In in vitro activity assays, N- and C-terminal truncations affected the catalytic efficiency of the enzyme different. Both the protease core alone and in combination with the N-terminal domain are over 100-fold less active than the full length enzyme, whereas a construct including the C-terminal region displays a rather small decrease in catalytic efficiency. Limited proteolysis experiments revealed that USP7 variants containing the C-terminal domain interact more tightly with ubiquitin. Besides playing an important role in substrate recognition and processing, this region might be involved in enzyme dimerization. USP7 constructs lacking the N-terminal domain failed to localize in the cell nucleus, but no nuclear localization signal could be mapped within the enzyme's first 70 amino acids. Instead, the tumor necrosis factor receptor associated factor-like region (amino acids 70-205) was sufficient to achieve the nuclear localization of the enzyme, suggesting that interaction partners might be required for USP7 nuclear import. 相似文献