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911.
Middleton J Americh L Gayon R Julien D Aguilar L Amalric F Girard JP 《Arthritis research & therapy》2004,6(2):60-72
Endothelial cells are active participants in chronic inflammatory diseases. These cells undergo phenotypic changes that can
be characterised as activated, angiogenic, apoptotic and leaky. In the present review, these phenotypes are described in the
context of human rheumatoid arthritis as the disease example. Endothelial cells become activated in rheumatoid arthritis pathophysiology,
expressing adhesion molecules and presenting chemokines, leading to leukocyte migration from the blood into the tissue. Endothelial
cell permeability increases, leading to oedema formation and swelling of the joints. These cells proliferate as part of the
angiogenic response and there is also a net increase in the turnover of endothelial cells since the number of apoptotic endothelial
cells increases. The endothelium expresses various cytokines, cytokine receptors and proteases that are involved in angiogenesis,
proliferation and tissue degradation. Associated with these mechanisms is a change in the spectrum of genes expressed, some
of which are relatively endothelial specific and others are widely expressed by other cells in the synovium. Better knowledge
of molecular and functional changes occurring in endothelial cells during chronic inflammation may lead to the development
of endothelium-targeted therapies for rheumatoid arthritis and other chronic inflammatory diseases. 相似文献
912.
Koopman WJ Verkaart S Visch HJ van der Westhuizen FH Murphy MP van den Heuvel LW Smeitink JA Willems PH 《American journal of physiology. Cell physiology》2005,288(6):C1440-C1450
Recent evidence indicates that oxidative stress is central to the pathogenesis of a wide variety of degenerative diseases, aging, and cancer. Oxidative stress occurs when the delicate balance between production and detoxification of reactive oxygen species is disturbed. Mammalian cells respond to this condition in several ways, among which is a change in mitochondrial morphology. In the present study, we have used rotenone, an inhibitor of complex I of the respiratory chain, which is thought to increase mitochondrial O(2)(-)* production, and mitoquinone (MitoQ), a mitochondria-targeted antioxidant, to investigate the relationship between mitochondrial O(2)(-)* production and morphology in human skin fibroblasts. Video-rate confocal microscopy of cells pulse loaded with the mitochondria-specific cation rhodamine 123, followed by automated analysis of mitochondrial morphology, revealed that chronic rotenone treatment (100 nM, 72 h) significantly increased mitochondrial length and branching without changing the number of mitochondria per cell. In addition, this treatment caused a twofold increase in lipid peroxidation as determined with C11-BODIPY(581/591). Finally, digital imaging microscopy of cells loaded with hydroethidine, which is oxidized by O(2)(-)* to yield fluorescent ethidium, revealed that chronic rotenone treatment caused a twofold increase in the rate of O(2)(-)* production. MitoQ (10 nM, 72 h) did not interfere with rotenone-induced ethidium formation but abolished rotenone-induced outgrowth and lipid peroxidation. These findings show that increased mitochondrial O(2)(-)* production as a consequence of, for instance, complex I inhibition leads to mitochondrial outgrowth and that MitoQ acts downstream of this O(2)(-)* to prevent alterations in mitochondrial morphology. 相似文献
913.
N-methyl-D-glucamine and propidium dyes utilize different permeation pathways at rat P2X(7) receptors 总被引:3,自引:0,他引:3
Jiang LH Rassendren F Mackenzie A Zhang YH Surprenant A North RA 《American journal of physiology. Cell physiology》2005,289(5):C1295-C1302
Activation of membrane P2X7 receptors by extracellular ATP [or its analog 2',3'-O-(4-benzoylbenzoyl)-ATP] results in the opening within several milliseconds of an integral ion channel that is permeable to small cations. If the ATP application is maintained for several seconds, two further sequelae occur: there is a gradual increase in permeability to the larger cation N-methyl-D-glucamine and the cationic propidium dye quinolinium, 4-[(3-methyl-2(3H)-benzoxazolylidene)methyl]-1-[3-(triethylammonio)propyl]diiodide (YO-PRO-1) enters the cell. The similarity in the time course of these two events has led to the widespread view that N-methyl-D-glucamine and YO-PRO-1 enter through a common permeation pathway, the "dilating" P2X7 receptor pore. Here we provide two independent lines of evidence against this view. We studied single human embryonic kidney cells expressing rat P2X7 receptors with patch-clamp recordings of membrane current and with fluorescence measurements of YO-PRO-1 uptake. First, we found that maintained application of the ATP analog did not cause any increase in N-methyl-D-glucamine permeability when the extracellular solution contained its normal sodium concentration, although YO-PRO-1 uptake was readily observed. Second, we deleted a cysteine-rich 18-amino acid segment in the intracellular juxtamembrane region of the P2X7 receptor. This mutated receptor showed normal YO-PRO-1 uptake but had no permeability to N-methyl-D-glucamine. Together, the clear differential effects of extracellular sodium ions or of mutation of the receptor strongly suggest that N-methyl-D-glucamine and YO-PRO-1 do not enter the cell by the same permeation pathway. ATP; cation channel; permeability; quinolinium, 4-[(3-methyl-2(3H)-benzoxazolylidene)methyl]-1-[3-(triethylammonio)propyl]diiodide 相似文献
914.
Interleukin-15 increases effector memory CD8+ t cells and NK Cells in simian immunodeficiency virus-infected macaques 下载免费PDF全文
Mueller YM Petrovas C Bojczuk PM Dimitriou ID Beer B Silvera P Villinger F Cairns JS Gracely EJ Lewis MG Katsikis PD 《Journal of virology》2005,79(8):4877-4885
Interleukin-15 (IL-15) in vitro treatment of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected individuals specifically enhances the function and survival of HIV-specific CD8+ T cells, while in vivo IL-15 treatment of mice preferentially expands memory CD8+ T cells. In this study, we investigated the in vivo effect of IL-15 treatment in 9 SIVmac251-infected cynomolgus macaques (low dose of IL-15, 10 microg/kg of body weight, n = 3; high dose of IL-15, 100 microg/kg, n = 3; control [saline], n = 3; dose administered twice weekly for 4 weeks). IL-15 treatment induced a nearly threefold increase in peripheral blood CD8+CD3- NK cells. Furthermore, CD8+ T-cell numbers increased more than twofold, mainly due to an increase in the CD45RA-CD62L- and CD45RA+CD62L- effector memory CD8+ T cells. Expression of Ki-67 in the CD8+ T cells indicated expansion of CD8+ T cells and not redistribution. IL-15 did not affect CD4+ T-cell, B-cell, and CD14+ macrophage numbers. No statistically significant differences in changes from baseline in the viral load were observed when control-, low-dose-, and high-dose-treated animals were compared. No clinical adverse effects were observed in any of the animals studied. The selective expansion of effector memory CD8+ T cells and NK cells by IL-15 further supports IL-15's possible therapeutic use in viral infections such as HIV infection. 相似文献
915.
Girard M Poupon V Blondeau F McPherson PS 《The Journal of biological chemistry》2005,280(48):40135-40143
Through a proteomic analysis of clathrin-coated vesicles from rat liver we identified the mammalian homolog of receptor-mediated endocytosis 8 (RME-8), a DnaJ domain-containing protein originally identified in a screen for endocytic defects in Caenorhabditis elegans. Mammalian RME-8 has a broad tissue distribution, and affinity selection assays reveal the ubiquitous chaperone Hsc70, which regulates protein conformation at diverse membrane sites as the major binding partner for its DnaJ domain. RME-8 is tightly associated with microsomal membranes and co-localizes with markers of the endosomal system. Small interfering RNA-mediated knock down of RME-8 has no influence on transferrin endocytosis but causes a reduction in epidermal growth factor internalization. Interestingly, and consistent with a localization to endosomes, knock down of RME-8 also leads to alterations in the trafficking of the cation-independent mannose 6-phosphate receptor and improper sorting of the lysosomal hydrolase cathepsin D. Our data demonstrate that RME-8 functions in intracellular trafficking and provides the first evidence of a functional role for a DnaJ domain-bearing co-chaperone on endosomes. 相似文献
916.
917.
Marquette CA Imbert-Laurenceau E Mallet F Chaix C Mandrand B Blum LJ 《Analytical biochemistry》2005,340(1):14-23
A serological chemiluminescent biochip was designed based on screen-printed electrode arrays composed of nine 1-mm(2) electrodes. Arrays were shown to be produced with good batch-to-batch reproducibility (standard deviations of 4.4 and 12.0% for ferricyanide oxidation potential and current, respectively) and very good reproducibility within a particular array (2.0 and 7.5% standard deviations for the same controls). Electrode arrays were used to electroaddress various bioconjugate structures comprising a recombinant HIV-1 P24 capsid protein (RH24K) in polypyrrole film. Entrapment of RH24K preimmobilized onto maleic anhydride-alt-methyl vinyl ether copolymer was shown to be the more efficient immobilization procedure. This addressed sensing layer enabled the detection of anti-P24 antibodies at a concentration of 3.5 ng/ml through peroxidase-labeled anti-human immunoglobulin G reaction. The biochip was used to perform an HIV-1 serological test in human sera. HIV-1 seropositive and seronegative sera were easily discriminated using serum dilutions greater than 1/10,000. 相似文献
918.
Daveau M Benard M Scotte M Schouft MT Hiron M Francois A Salier JP Fontaine M 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(5):3418-3424
Activation of the complement system generates the anaphylatoxin C5a whose activities are mediated through its binding to the widely expressed C5aR. C5aR mRNA and protein expressions are known to be induced in rat hepatocytes under inflammatory conditions. However, little is known about the role of the C5a/C5aR complex in liver and its involvement during a proliferative process. We have evaluated the expression of C5aR in regenerating rat hepatocytes following a partial hepatectomy and in hepatocyte cultures. C5aR induction was observed in hepatocytes from regenerating liver, as well as in normal hepatocytes under a culture-induced stress. The effect of a stimulation by a C5a agonist upon the synthesis of a growth factor/receptor pair (hepatocyte growth factor/c-Met) was also evaluated. Our data demonstrated an up-regulated expression of hepatocyte growth factor and c-Met mRNAs, but we failed to observe a direct mitogenic effect of C5a in culture. However, a significantly increased expression of cyclin E and D1mRNA levels, as well as an increased BrdU incorporation, were observed in rats given an i.v. C5a agonist injection following an 80% partial hepatectomy. These studies demonstrate for the first time that: 1) C5aR is up-regulated during liver regeneration, 2) the binding of C5a to C5aR promotes a growth response, and 3) C5aR is involved in a cell cycle signaling pathway. Taken together, these findings point to a novel role for the hepatic C5aR implicating this complement system in the context of normal or abnormal proliferative pathways. 相似文献
919.
920.
Erythrocyte storage may result in cell damage due to an alteration of membrane integrity, which results in potassium efflux and hemolysis. Lidocaine has been shown to protect erythrocytes from oxidative stress by a possible membrane effect. We conducted this study to examine the effects of lidocaine on human erythrocyte storage. Erythrocytes were kept for seven days at 04 degrees C in the absence or in presence of plasma, and of lidocaine at 36.9 and 221.6 microM. Cell damage was assessed by measuring potassium efflux in the supernatant after seven days, and studying potassium efflux and hemolysis induced by oxidative stress. As expected, erythrocyte storage in the presence of plasma was less deleterious. Lidocaine decreased potassium efflux after 7 days' storage. Resistance toward oxidative stress was greater when the erythrocytes had been kept in the presence of plasma. Considering that lidocaine is widely used in various clinical situations, this data may be of clinical relevance. 相似文献