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61.
62.
Christian Schiller Johanna E. HuberKalliope N. Diakopoulos Elisabeth H. Weiss 《Human immunology》2013
Carefully orchestrated intercellular communication is an essential prerequisite for an effective immune response. In recent years tunneling nanotubes (TNT) have emerged as a novel mechanism of cell–cell communication. These long membrane protrusions can establish cytoplasmic continuity between distant cells and enable the exchange of cellular components. In the present study we addressed the question whether these structures can facilitate the intercellular transfer of MHC class I molecules. We found a transmembrane HLA-A2-EGFP but not a soluble HLA-G1s-EGFP fusion protein to be effectively transferred between HeLa cells. Inhibition of actin polymerization significantly reduced the HLA-A2 transfer rate, indicating that transfer is dependent on tunneling nanotubes, whose de novo formation requires actin polymerization. Furthermore, overexpression of the nanotube-inducing protein LST1 promoted transfer of HLA-A2. Moreover, LST1 protein expression is enhanced in antigen presenting cells. Our results indicate that tunneling nanotubes can mediate transfer of MHC class I molecules between distant cells. 相似文献
63.
Human plasmacytoid dendritic cells (PDC) are blood dendritic cell antigen 2 (BDCA2) and blood dendritic cell antigen 4 (BDCA4) positive leukocytes that do not express common lineage markers. They have been described as proinflammatory innate immune cells and are the major source of αIFN in the human body. PDC-derived secretion of type I IFNs upon triggering of nucleic acid-sensing toll-like receptors (TLR) primes immune cells to rapidly respond to microbial stimuli and promotes a Th1 response. Here, we report that human PDC express CD36 and CD61 (β3 integrin), both involved in uptake of apoptotic cells and in induction of tolerance. Freshly isolated PDC and PDC within human blood leukocytes constitutively express IL-10. Thus, PDC may possess a so far neglected role in propagation of immune tolerance. 相似文献
64.
65.
Isolation and functional analysis of a human 70,000-dalton heat shock protein gene segment. 总被引:21,自引:0,他引:21
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R Voellmy A Ahmed P Schiller P Bromley D Rungger 《Proceedings of the National Academy of Sciences of the United States of America》1985,82(15):4949-4953
A human 70-kDa heat shock protein (hsp70) gene segment has been isolated. The segment contains 3.15 kilobase pairs (kbp) of 5' nontranscribed sequence, an RNA leader of 119 bp, and a protein-coding region of 741 bp. The human protein sequence shows a high degree of homology to hsp70 sequences from other species. Expression experiments in Xenopus oocytes and mammalian cells indicate that a region that includes only 105 bp of 5' nontranscribed sequence contains all elements required for the efficient heat-controlled expression of the human gene. Two adjacent identical sequence elements, which are partly homologous to the Drosophila "heat shock consensus" sequence, are located 57 to 76 bp upstream from the capping site. Interestingly, the capping site itself is flanked by inverted repeat sequences. 相似文献
66.
Hepcidin,a putative mediator of anemia of inflammation,is a type II acute-phase protein 总被引:36,自引:21,他引:36
Hepcidin is a liver-made peptide proposed to be a central regulator of intestinal iron absorption and iron recycling by macrophages. In animal models, hepcidin is induced by inflammation and iron loading, but its regulation in humans has not been studied. We report that urinary excretion of hepcidin was greatly increased in patients with iron overload, infections, or inflammatory diseases. Hepcidin excretion correlated well with serum ferritin levels, which are regulated by similar pathologic stimuli. In vitro iron loading of primary human hepatocytes, however, unexpectedly down-regulated hepcidin mRNA, suggesting that in vivo regulation of hepcidin expression by iron stores involves complex indirect effects. Hepcidin mRNA was dramatically induced by interleukin-6 (IL-6) in vitro, but not by IL-1 or tumor necrosis factor alpha (TNF-alpha), demonstrating that human hepcidin is a type II acute-phase reactant. The linkage of hepcidin induction to inflammation in humans supports its proposed role as a key mediator of anemia of inflammation. 相似文献
67.
69.
Stewart JD Marchan R Lesjak MS Lambert J Hergenroeder R Ellis JK Lau CH Keun HC Schmitz G Schiller J Eibisch M Hedberg C Waldmann H Lausch E Tanner B Sehouli J Sagemueller J Staude H Steiner E Hengstler JG 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(21):8155-8160
Metastasis from primary tumors remains a major problem for tumor therapy. In the search for markers of metastasis and more effective therapies, the tumor metabolome is relevant because of its importance to the malignant phenotype and metastatic capacity of tumor cells. Altered choline metabolism is a hallmark of cancer. More specifically, a decreased glycerophosphocholine (GPC) to phosphocholine (PC) ratio was reported in breast, ovarian, and prostate cancers. Improved strategies to exploit this altered choline metabolism are therefore required. However, the critical enzyme cleaving GPC to produce choline, the initial step in the pathway controlling the GPC/PC ratio, remained unknown. In the present work, we have identified the enzyme, here named EDI3 (endometrial differential 3). Purified recombinant EDI3 protein cleaves GPC to form glycerol-3-phosphate and choline. Silencing EDI3 in MCF-7 cells decreased this enzymatic activity, increased the intracellular GPC/PC ratio, and decreased downstream lipid metabolites. Downregulating EDI3 activity inhibited cell migration via disruption of the PKCα signaling pathway, with stable overexpression of EDI3 showing the opposite effect. EDI3 was originally identified in our screening study comparing mRNA levels in metastasizing and nonmetastasizing endometrial carcinomas. Both Kaplan-Meier and multivariate analyses revealed a negative association between high EDI3 expression and relapse-free survival time in both endometrial (P < 0.001) and ovarian (P = 0.029) cancers. Overall, we have identified EDI3, a key enzyme controlling GPC and choline metabolism. Because inhibition of EDI3 activity corrects the GPC/PC ratio and decreases the migration capacity of tumor cells, it represents a possible target for therapeutic intervention. 相似文献
70.
Jean-Sébastien Pelletier Christopher DeGara Geoff Porter Sunita Ghosh Dan Schiller 《Canadian journal of surgery》2013,56(4):E51-E58