The Experts below are selected from a list of 7875 Experts worldwide ranked by ideXlab platform
Almut Nebel - One of the best experts on this subject based on the ideXlab platform.
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allelic and copy number variations of fcγrs affect Granulocyte Function and susceptibility for autoimmune blistering diseases
Journal of Autoimmunity, 2015Co-Authors: Andreas Recke, Gestur Vidarsson, Ralf Ludwig, Miriam Freitag, Steffen Moller, Reinhard Vonthein, Julia Schellenberger, O Haase, Siegfried Gorg, Almut NebelAbstract:Low-affinity Fcγ receptors (FcγR) bridge innate and adaptive immune responses. In many autoimmune diseases, these receptors act as key mediators of the pathogenic effects of autoantibodies. Genes encoding FcγR exhibit frequent variations in sequence and gene copy number that influence their Functional properties. FcγR variations also affect the susceptibility to systemic autoimmunity, e.g. systemic lupus erythematosus and rheumatoid arthritis. This raises the question whether FcγR variations are also associated with organ-specific autoimmunity, particularly autoantibody-mediated diseases, such as subepidermal autoimmune blistering diseases (AIBD). A multitude of evidence suggests a pathogenic role of neutrophil Granulocyte interaction with autoantibodies via FcγR. In a two-stage study, we analyzed whether the FcγR genotype affects neutrophil Function and mRNA expression, and consequently, bullous pemphigoid (BP) disease risk. We compared this to findings in pemphigus vulgaris/foliaceus (PV/PF), two Fc-independent AIBDs. Our results indicate that both allele and copy number variation of FcγR genes affect FcγR mRNA expression and reactive oxygen species (ROS) release by Granulocytes. Susceptibility of BP was associated with FcγR genotypes that led to a decreased ROS release by neutrophils, indicating an unexpected protective role for these cells. BP and PV/PF differed substantially regarding the FcγR genotype association patterns, pointing towards different disease etiologies.
B Manger - One of the best experts on this subject based on the ideXlab platform.
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in vivo blockade of tnf alpha by intravenous infusion of a chimeric monoclonal tnf alpha antibody in patients with rheumatoid arthritis short term cellular and molecular effects
Journal of Immunology, 1996Co-Authors: Hannsmartin Lorenz, C Antoni, T Valerius, Roland Repp, M Grunke, N Schwerdtner, H Nusslein, James N Woody, Joachim R Kalden, B MangerAbstract:Due to the unknown etiology of RA, specific treatment is not available. Recently, in a double-blinded, placebo-controlled clinical trial, in vivo blockade of TNF-alpha by a single infusion of a chimeric TNF-alpha-blocking mAb, cA2, has proven to be highly effective in the treatment of RA. In parallel to this trial, we tested the consequences of cA2 infusion in ex vivo and in vitro experiments. In this paper, we describe an increase in CD4+ and CD8+ T lymphocyte counts on day 1 and a marked decrease in monocyte counts preferentially on day 7 after cA2 treatment, without major changes in B lymphocyte or NK cell counts. In addition, we found an increased responsiveness of PBMC to CD28 mAb/PMA, but not to CD3 mAb, superantigen staphylococcus enterotoxin B, or PHA on day 1 after infusion. The increase in DNA synthesis of PBMC was paralleled by increased IL-2 mRNA and IL-4 mRNA expression and IL-2 protein secretion in culture supernatants after in vitro stimulation of PBMC with CD28 mAb/PMA. In PBMC, we did not find any significant changes in mRNA or protein expression of CD28 Ag or CD28 ligands, B7-1 and B7-2. Serum concentrations of IL-1 beta, IL-6, and soluble CD14 were significantly diminished after in vivo TNF-alpha blockade. We did not see relevant changes in Granulocyte Function in vitro after cA2 infusion. Finally, we observed a statistically significant decrease in slCAM-1 molecules in the serum of patients treated with verum compared with that in the serum of subjects given placebo. This change in slCAM-1 concentration was evident on days 1 and 7 after the infusion of 10 mg/kg cA2, whereas it occurred only on day 7 in the serum of patients treated with the low dose (1 mg/kg) of cA2.
Andreas Recke - One of the best experts on this subject based on the ideXlab platform.
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allelic and copy number variations of fcγrs affect Granulocyte Function and susceptibility for autoimmune blistering diseases
Journal of Autoimmunity, 2015Co-Authors: Andreas Recke, Gestur Vidarsson, Ralf Ludwig, Miriam Freitag, Steffen Moller, Reinhard Vonthein, Julia Schellenberger, O Haase, Siegfried Gorg, Almut NebelAbstract:Low-affinity Fcγ receptors (FcγR) bridge innate and adaptive immune responses. In many autoimmune diseases, these receptors act as key mediators of the pathogenic effects of autoantibodies. Genes encoding FcγR exhibit frequent variations in sequence and gene copy number that influence their Functional properties. FcγR variations also affect the susceptibility to systemic autoimmunity, e.g. systemic lupus erythematosus and rheumatoid arthritis. This raises the question whether FcγR variations are also associated with organ-specific autoimmunity, particularly autoantibody-mediated diseases, such as subepidermal autoimmune blistering diseases (AIBD). A multitude of evidence suggests a pathogenic role of neutrophil Granulocyte interaction with autoantibodies via FcγR. In a two-stage study, we analyzed whether the FcγR genotype affects neutrophil Function and mRNA expression, and consequently, bullous pemphigoid (BP) disease risk. We compared this to findings in pemphigus vulgaris/foliaceus (PV/PF), two Fc-independent AIBDs. Our results indicate that both allele and copy number variation of FcγR genes affect FcγR mRNA expression and reactive oxygen species (ROS) release by Granulocytes. Susceptibility of BP was associated with FcγR genotypes that led to a decreased ROS release by neutrophils, indicating an unexpected protective role for these cells. BP and PV/PF differed substantially regarding the FcγR genotype association patterns, pointing towards different disease etiologies.
Fernando D Camargo - One of the best experts on this subject based on the ideXlab platform.
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regulation of progenitor cell proliferation and Granulocyte Function by microrna 223
Nature, 2008Co-Authors: Jonathan B Johnnidis, Marian H Harris, Robert T Wheeler, Sandra Stehlingsun, Michael H Lam, Oktay Kirak, Thijn R Brummelkamp, Mark D Fleming, Fernando D CamargoAbstract:MicroRNAs are abundant in animal genomes and have been predicted to have important roles in a broad range of gene expression programmes1,2. Despite this prominence, there is a dearth of Functional knowledge regarding individual mammalian microRNAs. Using a loss-of-Function allele in mice, we report here that the myeloid-specific microRNA-223 (miR-223) negatively regulates progenitor proliferation and Granulocyte differentiation and activation. miR-223 (also called Mirn223) mutant mice have an expanded granulocytic compartment resulting from a cell-autonomous increase in the number of Granulocyte progenitors. We show that Mef2c, a transcription factor that promotes myeloid progenitor proliferation, is a target of miR-223, and that genetic ablation of Mef2c suppresses progenitor expansion and corrects the neutrophilic phenotype in miR-223 null mice. In addition, Granulocytes lacking miR-223 are hypermature, hypersensitive to activating stimuli and display increased fungicidal activity. As a consequence of this neutrophil hyperactivity, miR-223 mutant mice spontaneously develop inflammatory lung pathology and exhibit exaggerated tissue destruction after endotoxin challenge. Our data support a model in which miR-223 acts as a fine-tuner of Granulocyte production and the inflammatory response.
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regulation of progenitor cell proliferation and Granulocyte Function by microrna 223
Blood, 2007Co-Authors: Fernando D Camargo, Jonathan B Johnnidis, Marian H Harris, Robert T Wheeler, Sandra Stehlingsun, Oktay Kirak, Michael Lam, Mark D FlemingAbstract:MicroRNAs are abundant in animal genomes and have been predicted to have important roles in a broad range of gene expression programs. Despite this prominence, there is a dearth of Functional knowledge regarding individual mammalian microRNAs. Using a loss-of-Function allele in mice, we report here that the myeloid-specific microRNA-223 (miR-223) negatively regulates progenitor proliferation and Granulocyte differentiation and activation. miR-223 mutant mice have an expanded granulocytic compartment resulting from a specific and cell-autonomous increase in the number of Granulocyte-monocyte progenitors (GMPs). We show that Mef2c, a transcription factor that promotes GMP renewal, is a target of miR-223 and that genetic ablation of Mef2c suppresses progenitor expansion and corrects the neutrophilic phenotype in miR-223 null mice. In addition, Granulocytes lacking miR-223 are hypermature, hypersensitive to activating stimuli and display increased fungicidal activity. Consequent to this neutrophil hyperactivity, miR-223 mutant mice spontaneously develop inflammatory lung pathology and exhibit exaggerated tissue destruction following endotoxin challenge. Our results present a new paradigm in miRNA-mediated gene regulation, in which a microRNA can negatively modulate the proliferation and differentiation program of the lineage to which it is most strongly associated.
William C Zamboni - One of the best experts on this subject based on the ideXlab platform.
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abstract 3697 evaluation of monocyte and Granulocyte Function with and without ex vivo pegylated liposomal doxorubicin pld exposure in blood of healthy volunteers
Cancer Research, 2010Co-Authors: Whitney P Caron, Ninh M Labeck, Alan M Fong, Peng Liu, Suzan K Hanna, Tuongvy L Ngo, Beth A Zamboni, Paola A Gehrig, Teresa K Tarrant, William C ZamboniAbstract:Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Background: PLD is a nanoparticle approved for treatment of refractory ovarian cancer. The reticuloendothelial system (RES), which includes monocytes (MO), may have a key role in clearance (CL) of nanoparticle sized pegylated liposomes such as PLD, though factors affecting the CL of liposomes are unclear. Previously we reported that the CL of liposomes is associated with age and monocyte counts. This study's objective was to characterize the Function of MO and Granulocytes with and without ex vivo PLD exposure in the blood of healthy volunteers. Methods: Blood samples were obtained from six (4 males, 2 females) healthy human volunteers, immediately placed on ice and processed. Blood samples were incubated with PLD 10 mcg/mL or 5% dextrose solution (control) for 1 hour (h) at 37°C with 5% CO2. After incubation, PHAGOTEST® and PHAGOBURST® (Orpegen Pharma) tests were performed to evaluate phagocytic activity and respiratory burst activity. PHAGOBURST® tests were performed after fMLP and PMA stimulation. Samples were analyzed using Dako CyAn Flow Cytometer with Summit software. Comparisons were made between samples with and without PLD exposure, gender, and age >60 and <60 years old (yo) based on previously reported trends. Results: The mean + SD age of healthy volunteers was 45.9 + 14.9 yo. The mean fluorescence per cell, grouped by Functional test and age, gender, and with or without PLD exposure are summarized in Table [1][1]. View this table: Table 1. Mean Fluorescence Conclusions: Differences in phagocytic and respiratory burst activity in Granulocytes and MO of healthy volunteers were observed. There is variability in activity based on the type of assay used. There appears to be both age and gender differences in activity. A 1 h ex vivo exposure to PLD does not seem to significantly alter cell Function. Future studies will characterize MO and Granulocyte Function, PLD uptake, and viability with and without PLD exposure in additional healthy subjects and ovarian and breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3697. [1]: #T1
