A5046920761- Sphingolipid Metabolism and Signaling
- Lipid Membrane Structure and Behavior
- Erythrocyte Function and Pathophysiology
- Inflammasome and immune disorders
- Lysosomal Storage Disorders Research
- Immune Cell Function and Interaction
- Cellular transport and secretion
- Sepsis Diagnosis and Treatment
- Autophagy in Disease and Therapy
- Pancreatitis Pathology and Treatment
- Cholesterol and Lipid Metabolism
- Platelet Disorders and Treatments
- Receptor Mechanisms and Signaling
- Drug Transport and Resistance Mechanisms
- Biomedical Research and Pathophysiology
- Alzheimer's disease research and treatments
- Lipid metabolism and biosynthesis
- Ion Transport and Channel Regulation
- Phagocytosis and Immune Regulation
- Pancreatic function and diabetes
- Immune cells in cancer
- Antifungal resistance and susceptibility
- Endoplasmic Reticulum Stress and Disease
- Carbohydrate Chemistry and Synthesis
- Caveolin-1 and cellular processes
Jena University Hospital
2016-2025
Friedrich Schiller University Jena
2024-2025
Universitätsmedizin Greifswald
2018
Charité - Universitätsmedizin Berlin
2010-2014
MSB Medical School Berlin
2012-2014
Max Delbrück Center
1998-2011
Medizinische Hochschule Hannover
2005-2011
Institute of Immunology
2007
University of California, San Francisco
2004
University of California San Francisco Medical Center
2002-2004
FTY720 is an immunosuppressant that reduces circulating levels of naïve lymphocytes by increasing their localization and sequestration in secondary lymphoid organs. It considered to be agonist for sphingosine 1-phosphate (S1P) G protein-coupled receptors (GPCRs) after phosphorylation at micromolar concentrations. We now describe its nonagonist noncompetitive inhibitory activity low nanomolar concentrations types 1 5 S1P-GPCRs moderate potency type 2 S1P-GPCRs. blocks S1P signaling through...
The blood constituent sphingosine 1-phosphate (S1P) is a specific ligand for five G-protein-coupled receptors designated S1P(1-5). Expression of the S1P1 receptor on lymphocytes required their exit from secondary lymphoid organs, suggesting that S1P serves as stimulus maintaining lymphocyte circulation in blood. Despite its potential role immune surveillance, regulatory system controls levels not well understood. This report reveals erythrocytes constitute buffer They efficiently...
The role of sphingosine-1-phosphate (S1P) and its receptors in the pathogenesis atherosclerosis has not been investigated.We hypothesized that S1P receptor 3 (S1P(3)) plays a causal atherosclerosis.We examined atherosclerotic lesion development mice deficient for S1P(3) apolipoprotein (Apo)E. Although deficiency did affect size after 25 or 45 weeks normal chow diet, it resulted dramatic reduction monocyte/macrophage content lesions S1P(3)(-/-)/ApoE(-/-) double knockout mice. To search...
Abstract Sphingosine 1‐phosphate (S1P) in blood is phosphorylated, stored, and transported by red cells (RBC). Release of S1P from RBC into plasma a regulated process that does not occur plasma‐ or serum‐free media. Plasma fractionation incubations with isolated recombinant proteins identified high density lipoprotein (HDL) serum albumin (SA) as non‐redundant endogenous triggers for release RBC. bound to SA HDL was able stimulate the 1 receptor calcium flux experiments. The binding...
Abstract Acute lung injury (ALI) is a severe inflammatory disease for which no specific treatment exists. As glucocorticoids have potent immunosuppressive effects, their application in ALI currently being tested clinical trials. However, the benefits of this type regimen remain unclear. Here we identify mechanism glucocorticoid action that challenges long-standing dogma cytokine repression by receptor. Contrarily, synergistic gene induction sphingosine kinase 1 ( SphK1 ) and pro-inflammatory...
Macroautophagy/autophagy defects have been identified as critical factors underlying the pathogenesis of neurodegenerative diseases. The roles bioactive signaling lipid sphingosine-1-phosphate (S1P) and its catabolic enzyme SGPL1/SPL (sphingosine phosphate lyase 1) in autophagy are increasingly recognized. Here we provide vitro vivo evidence for a previously unidentified route through which SGPL1 modulates neurons. cleaves S1P into ethanolamine phosphate, is directed toward synthesis...
Abstract Sphingosine-1-phosphate (S1P) participates in inflammation; however, its role leukocyte rolling is still unclear. Here we use intravital microscopy inflamed mouse cremaster muscle venules and human endothelial cells to show that S1P contributes P-selectin-dependent through receptor 3 (S1P ) Gα q , PLCβ Ca 2+ . Intra-arterial administration increases rolling, while deficiency or inhibition dramatically reduces it. Mast involved triggering also release mobilizes P-selectin Histamine...
Although predominantly expressed on lymphocytic and hematopoietic cells, the role of sphin-gosine-1-phospate receptor 4 (S1P4) in immune homeostasis is still poorly understood. In this report, we used a S1P4-deficient murine model to characterize biological S1P4-mediated S1P signaling system. S1p4-/- animals showed normal peripheral lymphocyte numbers regular architecture secondary lymphoid organs. Interestingly, S1P4 only marginally affects T-cell function vivo. contrast, dendritic cell...
Background: We have recently demonstrated a reduction in HDL-bound sphingosine 1-phosphate (S1P) patients with stable coronary artery disease (CAD). In the current study, we tested whether HDL-associated S1P is predictive for degree of stenosis, restenosis and overall CAD severity on follow up undergoing elective percutaneous intervention (PCI). Methods: Coronary angiography (n=59) PCI presenting after 6 months (n=48) was graded defined clinically as 1- or multi-vessel disease. Target lesion...
Abstract Microglia mediated responses to neuronal damage in the form of neuroinflammation is a common thread propagating neuropathology. In this study, we investigated microglial alterations occurring as result sphingosine 1‐phosphate (S1P) accumulation neural cells. We evidenced increased activation brains S1P‐lyase (SGPL1) ablated mice (SGPL1 fl/fl/Nes ) shown by an activated and deramified morphology markers on microglia. addition, increase pro‐inflammatory cytokines sorted primary...
Lipid rafts form signaling platforms on biological membranes with incompletely characterized role in immune response to infection. Here we report that lipid-raft microdomains are essential components of phagolysosomal macrophages and depend flotillins. Genetic deletion flotillins demonstrates the assembly both major defense complexes vATPase NADPH oxidase requires membrane microdomains. Furthermore, describe a virulence mechanism leading dysregulation by melanized wild-type conidia important...
Abstract Insulin resistance (IR) during obesity is linked to adipose tissue macrophage (ATM)-driven inflammation of tissue. Whether anti-inflammatory glucocorticoids (GCs) at physiological levels modulate IR unclear. Here, we report that deletion the GC receptor (GR) in myeloid cells, including macrophages mice, aggravates obesity-related by enhancing due decreased ATM leading exaggerated lipolysis and severe hepatic steatosis. In contrast, GR Kupffer cells alone does not alter IR....
Sepsis is characterized as life-threatening organ dysfunction caused by a dysregulated host response to an infection. Despite numerous clinical trials that addressed this syndrome, there still no causative treatment available dampen its severity. Curtailing the infection at early stage with anti-infectives only effective regime besides intensive care. In search for additional options, we recently discovered inhibition of sphingosine 1-phosphate (S1P) lyase and subsequent activation S1P...
Sphingosine 1-phosphate (S1P) receptors represent a novel subfamily of G-protein-coupled binding S1P specifically and with high affinity. Although their in vivo functions remain largely unknown, vitro extracellular application induces distinct receptor-dependent cellular responses including proliferation, differentiation, migration. We have analyzed signaling pathways engaged by S1P(4), which is highly expressed the lymphoid system. Here we show that S1P(4) couples directly to Galpha(i) even...
Megakaryocytes, which mature from hematopoietic progenitors in the bone marrow, further differentiate by reorganizing their cytoplasm into long proplatelet extensions that release platelets circulation. The molecular mechanisms underlying this highly dynamic cytoplasmic and cytoskeletal remodeling process are only poorly understood. Here we report sphingosine 1-phosphate receptor 4 (S1P(4)) is specifically up-regulated during development of human megakaryocytes progenitor cells expressed...
Sphingosine kinases (SKs) 1 and 2 produce high concentrations of sphingosine 1-phosphate (S1P) in blood lymph. In contrast, S1P lymphoid tissues are kept low by the S1P-degrading activity S1P-lyase. These differences drive lymphocyte circulation. Inhibition S1P-lyase prevents egress causes lymphopenia because increased levels tissues. this study, we investigated source accumulating using SK2-deficient (SK2(-/-)) mice. contrast to wild-type mice, SK2(-/-) mice exhibited attenuated after...