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Dive into the research topics where Evelyn Orsó is active.

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Featured researches published by Evelyn Orsó.


Nature Genetics | 1999

The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease.

Marek Bodzioch; Evelyn Orsó; Jochen Klucken; Thomas Langmann; Alfred Böttcher; Wendy Diederich; Wolfgang Drobnik; Stefan Barlage; Christa Büchler; Mustafa Porsch-Özcürümez; Wolfgang E. Kaminski; Harry W. Hahmann; Kurt Oette; Gregor Rothe; Charalampos Aslanidis; Karl J. Lackner; Gerd Schmitz

Tangier disease (TD) is an autosomal recessive disorder of lipid metabolism. It is characterized by absence of plasma high-density lipoprotein (HDL) and deposition of cholesteryl esters in the reticulo-endothelial system with splenomegaly and enlargement of tonsils and lymph nodes. Although low HDL cholesterol is associated with an increased risk for coronary artery disease, this condition is not consistently found in TD pedigrees. Metabolic studies in TD patients have revealed a rapid catabolism of HDL and its precursors. In contrast to normal mononuclear phagocytes (MNP), MNP from TD individuals degrade internalized HDL in unusual lysosomes, indicating a defect in cellular lipid metabolism. HDL-mediated cholesterol efflux and intracellular lipid trafficking and turnover are abnormal in TD fibroblasts, which have a reduced in vitro growth rate. The TD locus has been mapped to chromosome 9q31 (ref. 9). Here we present evidence that TD is caused by mutations in ABC1, encoding a member of the ATP-binding cassette (ABC) transporter family, located on chromosome 9q22–31 (ref. 10). We have analysed five kindreds with TD and identified seven different mutations, including three that are expected to impair the function of the gene product. The identification of ABC1 as the TD locus has implications for the understanding of cellular HDL metabolism and reverse cholesterol transport, and its association with premature cardiovascular disease.


Journal of Leukocyte Biology | 2000

Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro- and antiinflammatory stimuli.

Christa Buechler; Mirko Ritter; Evelyn Orsó; Thomas Langmann; Jochen Klucken; Gerd Schmitz

CD163, also referred to as M130, a member of the scavenger receptor cysteine‐rich family (SRCR) is exclusively expressed on cells of the monocyte lineage. In freshly isolated monocytes the CD14bight CD16+ monocyte subset revealed the highest expression of CD163 among all monocyte subsets. CD163 mRNA and protein expression is up‐regulated during macrophage colony‐stimulating factor (M‐CSF)‐dependent phagocytic differentiation of human blood monocytes. In contrast, monocytic cells treated with GM‐CSF and interleukin‐4 (IL‐4) for dendritic differentiation down‐regulate this antigen. CD163 expression is also suppressed by proinflammatory mediators like lipopolysaccharide (LPS), interferon‐γ (IFN‐γ), and tumor necrosis factor α, whereas IL‐6 and the antiinflammatory cytokine interleukin‐10 (IL‐10) strongly up‐regulate CD163 mRNA in monocytes and macrophages. The effects of the immunosuppressants dexamethasone, cyclosporin A (CA), and cortisol differ in their capacity to influence CD163 mRNA levels. Our results demonstrate that CD163 expression in monocytes/macrophages is regulated by proinflammatory and antiinflammatory mediators. This expression pattern implies a functional role of CD163 in the antiinflammatory response of monocytes. J. Leukoc. Biol. 67: 97–103; 2000.


Nature Genetics | 2000

Transport of lipids from golgi to plasma membrane is defective in tangier disease patients and Abc1-deficient mice.

Evelyn Orsó; Cyril Broccardo; Wolfgang E. Kaminski; Alfred Böttcher; Gerhard Liebisch; Wolfgang Drobnik; Alexandra Götz; Olivier Chambenoit; Wendy Diederich; Thomas Langmann; Thilo Spruss; Marie-Françoise Luciani; Gregor Rothe; Karl J. Lackner; Giovanna Chimini; Gerd Schmitz

Mutations in the gene encoding ATP-binding cassette transporter 1 ( ABC1) have been reported in Tangier disease (TD), an autosomal recessive disorder that is characterized by almost complete absence of plasma high-density lipoprotein (HDL), deposition of cholesteryl esters in the reticulo-endothelial system (RES) and aberrant cellular lipid trafficking. We demonstrate here that mice with a targeted inactivation of Abc1 display morphologic abnormalities and perturbations in their lipoprotein metabolism concordant with TD. ABC1 is expressed on the plasma membrane and the Golgi complex, mediates apo-AI associated export of cholesterol and phospholipids from the cell, and is regulated by cholesterol flux. Structural and functional abnormalities in caveolar processing and the trans-Golgi secretory pathway of cells lacking functional ABC1 indicate that lipid export processes involving vesicular budding between the Golgi and the plasma membrane are severely disturbed.


Proceedings of the National Academy of Sciences of the United States of America | 2002

Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues

Miranda Van Eck; I. Sophie T. Bos; Wolfgang E. Kaminski; Evelyn Orsó; Gregor Rothe; Jaap Twisk; Alfred Böttcher; Edwin S. Van Amersfoort; Trudy A. Christiansen-Weber; Wai-Ping Fung-Leung; Theo J.C. van Berkel; Gerd Schmitz

The ATP-binding cassette transporter 1 (ABCA1) has recently been identified as a key regulator of high-density lipoprotein (HDL) metabolism, which is defective in familial HDL-deficiency syndromes such as Tangier disease. ABCA1 functions as a facilitator of cellular cholesterol and phospholipid efflux, and its expression is induced during cholesterol uptake in macrophages. To assess the role of macrophage ABCA1 in atherosclerosis, we generated low-density lipoprotein (LDL) receptor knockout (LDLr−/−) mice that are selectively deficient in leukocyte ABCA1 (ABCA1−/−) by using bone marrow transfer (ABCA1−/− → LDLr−/−). Here we demonstrate that ABCA1−/− → LDLr−/− chimeras develop significantly larger and more advanced atherosclerotic lesions compared with chimeric LDLr−/− mice with functional ABCA1 in hematopoietic cells. Targeted disruption of leukocyte ABCA1 function did not affect plasma HDL cholesterol levels. The amount of macrophages in liver and spleen and peripheral blood leukocyte counts is increased in the ABCA1−/− → LDLr−/− chimeras. Our results provide evidence that leukocyte ABCA1 plays a critical role in the protection against atherosclerosis, and we identify ABCA1 as a leukocyte factor that controls the recruitment of inflammatory cells.


European Journal of Immunology | 2001

Lipopolysaccharide and ceramide docking to CD14 provokes ligand‐specific receptor clustering in rafts

Alexandra Pfeiffer; Alfred Böttcher; Evelyn Orsó; Michael Kapinsky; Péter Nagy; Andrea Bodnár; Ingo Spreitzer; Gerhard Liebisch; Wolfgang Drobnik; Klaus Gempel; Markus Horn; Stefan Holmer; Thomas Hartung; Gabriele Multhoff; Gerhard J. Schütz; Hansgeorg Schindler; Artur J. Ulmer; Holger Heine; Felix Stelter; Christine Schütt; Gregor Rothe; János Szöllosi; Sándor Damjanovich; Gerd Schmitz

The glycosylphosphatidylinositol‐anchored receptor CD14 plays a major role in the inflammatory response of monocytes to lipopolysaccharide. Here, we describe that ceramide, a constituent of atherogenic lipoproteins, binds to CD14 and induces clustering of CD14 to co‐receptors in rafts. In resting cells, CD14 was associated with CD55, the Fcγ‐receptors CD32 and CD64 and the pentaspan CD47. Ceramide further recruited the complement receptor 3 (CD11b/CD18) and CD36 into proximity of CD14. Lipopolysaccharide, in addition, induced co‐clustering with Toll‐like receptor 4, Fcγ‐RIIIa (CD16a) and the tetraspanin CD81 while CD47 was dissociated. The different receptor complexes may be linked to ligand‐specific cellular responses initiated by CD14.


Current Opinion in Lipidology | 2000

ABC transporters in cellular lipid trafficking.

Gerd Schmitz; Wolfgang E. Kaminski; Evelyn Orsó

ATP-binding cassette (ABC) transporters constitute a group of evolutionary highly conserved cellular transmembrane transport proteins. Recent work has implicated ABC transporters in cellular transmembrane lipid transport and hereditary diseases have been causatively linked to defective ABC transporters translocating lipid compounds. The emerging concept that a defined subset of ABC transporters is intimately involved in cellular lipid trafficking has recently been substantiated convincingly by the finding that ABCA1 plays a central role in the regulation of HDL metabolism and macrophage targeting to the RES or the vascular wall. Differentiation dependent expression of a large number of ABC transporters in monocytes/macrophages and their regulation by sterol flux render these transporter molecules potentially critical players in atherogenesis and other chronic inflammatory diseases.


Journal of Biological Chemistry | 2005

Aminopeptidase N (CD13) is a molecular target of the cholesterol absorption inhibitor ezetimibe in the enterocyte brush border membrane

Werner Prof. Dr. Kramer; Frank Girbig; Daniel Corsiero; Anja Pfenninger; Wendelin Frick; Gerhard Jähne; Matthias Rhein; Wolfgang Wendler; Friedrich Lottspeich; Elisabeth O. Hochleitner; Evelyn Orsó; Gerd Schmitz

Intestinal cholesterol absorption is an important regulator of serum cholesterol levels. Ezetimibe is a specific inhibitor of intestinal cholesterol absorption recently introduced into medical practice; its mechanism of action, however, is still unknown. Ezetimibe neither influences the release of cholesterol from mixed micelles in the gut lumen nor the transfer of cholesterol to the enterocyte brush border membrane. With membrane-impermeable Ezetimibe analogues we could demonstrate that binding of cholesterol absorption inhibitors to the brush border membrane of small intestinal enterocytes from the gut lumen is sufficient for inhibition of cholesterol absorption. A 145-kDa integral membrane protein was identified as the molecular target for cholesterol absorption inhibitors in the enterocyte brush border membrane by photoaffinity labeling with photoreactive Ezetimibe analogues (Kramer, W., Glombik, H., Petry, S., Heuer, H., Schäfer, H. L., Wendler, W., Corsiero, D., Girbig, F., and Weyland, C. (2000) FEBS Lett. 487, 293–297). The 145-kDa Ezetimibe-binding protein was purified by three different methods and sequencing revealed its identity with the membrane-bound ectoenzyme aminopeptidase N ((alanyl)aminopeptidase; EC 3.4.11.2; APN; leukemia antigen CD13). The enzymatic activity of APN was not influenced by Ezetimibe (analogues). The uptake of cholesterol delivered by mixed micelles by confluent CaCo-2 cells was partially inhibited by Ezetimibe and nonabsorbable Ezetimibe analogues. Preincubation of confluent CaCo-2 cells with Ezetimibe led to a strong decrease of fluorescent APN staining with a monoclonal antibody in the plasma membrane. Independent on its enzymatic activity, aminopeptidase N is involved in endocytotic processes like the uptake of viruses. Our findings suggest that binding of Ezetimibe to APN from the lumen of the small intestine blocks endocytosis of cholesterol-rich membrane microdomains, thereby limiting intestinal cholesterol absorption.


Current Opinion in Lipidology | 2002

CD14 signalling in lipid rafts: new ligands and co-receptors.

Gerd Schmitz; Evelyn Orsó

Purpose of review Lipid rafts on monocytes/macrophages provide a dynamic microenvironment for an integrated lipopolysaccharide receptor (CD14)-dependent clustering of a set of receptors involved in innate immunity and clearance of atherogenic lipoproteins. The purpose of this review is to summarize the recent advances in our understanding of CD14-dependent receptor clustering and its relevance in atherogenesis. Recent findings Upon binding of various ligands, CD14 as a multiligand pattern recognition receptor induces specific coassembly of additional receptors present on circulating monocytes. Summary The composition of the receptor cluster and thus the associated signalling pathways defines a ligand specific cellular response, linking endogenous and exogenous host defense to a common recognition platform in rafts.


Biochimica et Biophysica Acta | 2001

Adipophilin is a sensitive marker for lipid loading in human blood monocytes

Christa Buechler; Mirko Ritter; Chinh Quoc Duong; Evelyn Orsó; Michael Kapinsky; Gerd Schmitz

Adipophilin, a marker of lipid accumulation initially described in adipocytes, was recently shown to be induced in macrophage foam cells. We found that even freshly isolated blood monocytes express adipophilin and that the amount of adipophilin protein is variable in monocytes from different healthy individuals. However, the physiological expression of adipophilin does not correlate with the levels of free fatty acids, cholesterylesters or free cholesterol. Enzymatically modified low-density lipoprotein (E-LDL) induces rapid foam cell formation in monocytes and upregulates adipophilin mRNA and protein within 2 h of incubation. This rapid induction of adipophilin is accompanied by a significant increase of free fatty acids in monocytes incubated with E-LDL. Adipophilin facilitates the uptake of free fatty acids, and here we demonstrate that free fatty acids increase is related to the early upregulation of adipophilin expression in blood monocytes. Fatty acids are ligands for peroxisome proliferator-activated receptor-gamma (PPARgamma), and the upregulation of adipophilin mRNA by PPARgamma agonists like 15d-PGJ(2) and ciglitazone indicates that PPARgamma may mediate the induction of adipophilin expression in human blood monocytes.


Cytotherapy | 2009

Harvesting human adipose tissue-derived adult stem cells: resection versus liposuction

Stephan Schreml; Philipp Babilas; Sabine Fruth; Evelyn Orsó; Gerd Schmitz; Michael B. Mueller; Michael Nerlich; Lukas Prantl

BACKGROUND Adipose tissue is an abundant source of mesenchymal stem cells (MSC), which can be used for tissue-engineering purposes. The aim of our study was to determine the more suitable procedure, surgical resection or liposuction, for harvesting human adipose tissue-derived stem cells (hASC) with regard to viability, cell count and differentiation potential. METHODS After harvesting hASC, trypan blue staining and cell counting were carried out. Subsequently, hASC were cultured, analyzed by fluorescence-activated cell sorting (FACS) and differentiated under adipogenic, osteogenic and chondrogenic conditions. Histologic and functional analyzes were performed at the end of the differentiation period. RESULTS No significant difference was found with regard to the cell counts of hASC from liposuction and surgically resected material (P=0.086). The percentage of viable cells was significantly higher for liposuction aspirates than for resection material (P=0.002). No significant difference was found in the adipogenic differentiation potential (P=0.179). A significantly lower number of cultures obtained from liposuction material than from resection material could be differentiated into osteocytes (P=0.049) and chondrocytes (P=0.012). DISCUSSION Even though some lineages from lipoaspirated hASC can not be differentiated as frequently as those from surgically resected material, liposuction may be superior for some tissue-engineering purposes, particularly because of the less invasive harvesting procedure, the higher percentage of viable cells and the fact that there is no significant difference between lipoaspirated and resected hASC with regard to adipogenic differentiation potential.

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Gerd Schmitz

University of Regensburg

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Gregor Rothe

University of Regensburg

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Jochen Klucken

University of Erlangen-Nuremberg

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Margot Grandl

University of Regensburg

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