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Liang Gao, Gülce Sila Gülcüler, Lieke Golbach, Helena Block, Alexander Zarbock, Ana Martin-Villalba
Integrin activation is crucial for regulation of leukocyte rolling, adhesion and trans-vessel migration during inflammation and occurs by engagement of myeloid cells through factors presented by inflamed vessels. However, endothelial-dependent mechanisms of myeloid cell recruitment are not fully understood. Here we show using an autoperfused flow chamber assay of whole blood neutrophils and intravital microscopy of the inflamed cremaster muscle that CD95 mediates leukocyte slow rolling, adhesion and transmigration upon binding of CD95-ligand (CD95L) that is presented by endothelial cells...
October 20, 2016: ELife
Joanna Collison
No abstract text is available yet for this article.
September 2016: Nature Reviews. Rheumatology
Amanda Poissonnier, Doriane Sanséau, Matthieu Le Gallo, Marine Malleter, Nicolas Levoin, Roselyne Viel, Lucie Morere, Aubin Penna, Patrick Blanco, Alain Dupuy, Florence Poizeau, Alain Fautrel, Julien Seneschal, Florence Jouan, Jerome Ritz, Edouard Forcade, Nathalie Rioux, Cécile Contin-Bordes, Thomas Ducret, Anne-Marie Vacher, Paul A Barrow, Robin J Flynn, Pierre Vacher, Patrick Legembre
CD95 ligand (CD95L) is expressed by immune cells and triggers apoptotic death. Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but does not trigger apoptotic signaling. Hence, the pathophysiological role of cl-CD95L remains unclear. We observed that skin-derived endothelial cells from systemic lupus erythematosus (SLE) patients expressed CD95L and that after cleavage, cl-CD95L promoted T helper 17 (Th17) lymphocyte transmigration across the endothelial barrier at the expense of T regulatory cells...
July 19, 2016: Immunity
A Fouqué, E Lepvrier, L Debure, Y Gouriou, M Malleter, V Delcroix, M Ovize, T Ducret, C Li, M Hammadi, P Vacher, P Legembre
Metalloprotease-processed CD95L (cl-CD95L) is a soluble cytokine that implements a PI3K/Ca(2+) signaling pathway in triple-negative breast cancer (TNBC) cells. Accordingly, high levels of cl-CD95L in TNBC women correlate with poor prognosis, and administration of this ligand in an orthotopic xenograft mouse model accelerates the metastatic dissemination of TNBC cells. The molecular mechanism underlying CD95-mediated cell migration remains unknown. Here, we present genetic and pharmacologic evidence that the anti-apoptotic molecules BclxL and Bcl-2 and the pro-apoptotic factors BAD and BID cooperate to promote migration of TNBC cells stimulated with cl-CD95L...
October 2016: Cell Death and Differentiation
Ha-Yeun Chung, Daniel C Hupe, Gordon P Otto, Marcel Sprenger, Alexander C Bunck, Michael J Dorer, Clemens L Bockmeyer, Hans-Peter Deigner, Markus H Gräler, Ralf A Claus
The pathophysiology of sepsis involves activation of acid sphingomyelinase (SMPD1) with subsequent generation of the bioactive mediator ceramide. We herein evaluated the hypothesis that the enzyme exerts biological effects in endothelial stress response. Plasma-secreted sphingomyelinase activity, ceramide generation and lipid raft formation were measured in human microcirculatory endothelial cells (HMEC-1) stimulated with serum obtained from sepsis patients. Clustering of receptors relevant for signal transduction was studied by immuno staining...
June 15, 2016: Molecular Medicine
Michael Monet, Mallorie Poët, Sébastien Tauzin, Amélie Fouqué, Auréa Cophignon, Dominique Lagadic-Gossmann, Pierre Vacher, Patrick Legembre, Laurent Counillon
Transmembrane CD95L (Fas ligand) can be cleaved to release a promigratory soluble ligand, cl-CD95L, which can contribute to chronic inflammation and cancer cell dissemination. The motility signaling pathway elicited by cl-CD95L remains poorly defined. Here, we show that in the presence of cl-CD95L, CD95 activates the Akt and RhoA signaling pathways, which together orchestrate an allosteric activation of the Na(+)/H(+) exchanger NHE1. Pharmacologic inhibition of Akt or ROCK1 independently blocks the cl-CD95L-induced migration...
2016: Scientific Reports
C M Lin, R J Plenter, M Coulombe, R G Gill
Natural killer (NK) cells are key components of the innate immune system. In murine cardiac transplant models, donor-specific antibodies (DSA), in concert with NK cells, are sufficient to inflict chronic allograft vasculopathy independently of T and B cells. In this study, we aimed to determine the effector mechanism(s) required by NK cells to trigger chronic allograft vasculopathy during antibody-mediated rejection. Specifically, we tested the relative contribution of the proinflammatory cytokine interferon gamma (IFN-γ) versus the contact-dependent cytotoxic mediators of perforin and the CD95/CD95L (Fas/Fas ligand [FasL]) pathway for triggering these lesions...
May 10, 2016: American Journal of Transplantation
A Moghaddam, A Sperl, R Heller, H J Gerner, B Biglari
STUDY DESIGN: A prospective observational study reporting correlation between sCD95L (serum cluster of differentiation 95 ligand) serum levels and remission after traumatic spinal cord injury (SCI). OBJECTIVES: To describe the correlation between sCD95L serum levels and remission after traumatic SCI in a human protocol compared with animal studies. SETTING: Rhineland-Palatinate (Rheinland-Pfalz), Germany. METHODS: We included 45 patients with traumatic SCI...
April 19, 2016: Spinal Cord
Jaime F Modiano, Donald Bellgrau
Fas ligand (FasL, CD95L) is a 40-kDa type II transmembrane protein that binds to Fas (CD95) receptors and promotes programmed cell death. Fas receptors are expressed at higher levels in many tumors than in normal cells; however, systemic administration of FasL or agonistic anti-Fas antibodies to mice with tumors caused lethal hepatitis. Somewhat paradoxically, elimination of Fas or FasL from tumors also leads to death induced by CD95 receptor/ligand elimination (DICE). At face value, this suggests that Fas signaling not only kills normal cells, but that it also is essential for tumor cell survival...
February 2016: Discovery Medicine
Anna Raimbault, Cecile Pierre-Eugene, Alexandra Rouquette, Celine Deudon, Lise Willems, Nicolas Chapuis, Stephanie Mathis, Claudia Kunz, Harald Fricke, Olivier Kosmider, Valerie Bardet, Michaela Fontenay
CD95, a member of the death receptor family initiates a caspase-dependent apoptosis, when activated by its ligand CD95L, thought to negatively regulate erythrocyte production in the bone marrow. We have previously shown that CD95 is overexpressed in two thirds of patients with a lower risk myelodysplastic syndrome (MDS) and that resistance to erythropoiesis-stimulating agents (ESA) is linked to poor residual erythropoiesis. In the present study, we show that CD95 overexpression and previous transfusion are independent predictive factors of ESA resistance...
March 22, 2016: Oncotarget
Kari Trumpi, Ernst J A Steller, Wendy W de Leng, Daniëlle A Raats, Isaäc J Nijman, Folkert H M Morsink, Inne H M Borel Rinkes, Onno Kranenburg
Homeostasis of the continuously self-renewing intestinal tract involves cell proliferation, migration, differentiation along the crypt-villus-axis and shedding of cells into the gut lumen. CD95-ligand (FAS-ligand, CD95L) is a cytokine that is known for its capacity to induce apoptosis by binding its cognate receptor, CD95 (Fas). More recently, it was discovered that CD95L can also induce other cellular responses, such as proliferation, differentiation and cell migration. CD95L is highly expressed in Paneth cells of the small intestine which are in close contact with intestinal stem cells...
June 2016: Medical Molecular Morphology
Clarissa Liesche, Kristin S Grussmayer, Michael Ludwig, Stefan Wörz, Karl Rohr, Dirk-Peter Herten, Joël Beaudouin, Roland Eils
The number of fluorophores within a molecule complex can be revealed by single-molecule photobleaching imaging. A widely applied strategy to analyze intensity traces over time is the quantification of photobleaching step counts. However, several factors can limit and bias the detection of photobleaching steps, including noise, high numbers of fluorophores, and the possibility that several photobleaching events occur almost simultaneously. In this study, we propose a new approach, to our knowledge, to determine the fluorophore number that correlates the intensity decay of a population of molecule complexes with the decay of the number of visible complexes...
December 1, 2015: Biophysical Journal
Xiuwen Yi, Yirong Cai, Wenxian Li
Background. Isoflurane disrupts brain development of neonatal mice, but its mechanism is unclear. We explored whether isoflurane damaged developing hippocampi through FASL-FAS signaling pathway, which is a well-known pathway of apoptosis. Method. Wild type and FAS- or FASL-gene-knockout mice aged 7 days were exposed to either isoflurane or pure oxygen. We used western blotting to study expressions of caspase-3, FAS (CD95), and FAS ligand (FASL or CD95L) proteins, TUNEL staining to count apoptotic cells in hippocampus, and Morris water maze (MWM) to evaluate learning and memory...
2015: BioMed Research International
Sabine Pietkiewicz, Roland Eils, Peter H Krammer, Natalia Giese, Inna N Lavrik
Combination therapy of cancer is based on the cumulative effects mediated by several drugs. Although molecular mechanisms of action of each particular drug are partially elucidated, understanding of the dynamic cross-talk between different cell death pathways at the quantitative level induced by combination therapy is still missing. Here, we exemplified this question for the death receptor (DR) networks in pancreatic cancer cells. We demonstrate that the combined action of CD95L and gemcitabine in pancreatic cancer cells leads to the simultaneous induction of caspase-dependent and caspase-independent cell death...
November 15, 2015: Experimental Cell Research
Piotr Bartnicki, Ewa Majewska, Mariusz Kowalczyk, Zbigniew Baj, Maciej Banach, Jacek Rysz
BACKGROUND: Some data in literature indicate increased apoptosis of polymorphonuclear cells (PMNs) in chronic kidney disease (CKD), what seems to be connected with anemia. Erythropoiesis-stimulating agents, used in anemia treatment in CKD may affect cells apoptosis. Aim of this study was to investigate impact of anemia treatment with methoxy polyethylene glycol-epoetin beta (CERA) on PMNs apoptosis in predialysis patients with CKD. METHODS: Percentage of early and late apoptotic PMNs was measured by flow cytometry based on annexin V and propidium iodide binding...
October 2015: Pharmacological Reports: PR
Caroline E Broos, Menno van Nimwegen, Alex Kleinjan, Bregje ten Berge, Femke Muskens, Johannes C C M in 't Veen, Jouke T Annema, Bart N Lambrecht, Henk C Hoogsteden, Rudi W Hendriks, Mirjam Kool, Bernt van den Blink
BACKGROUND: Impaired regulatory T cell (Treg) function is thought to contribute to ongoing inflammatory responses in sarcoidosis, but underlying mechanisms remain unclear. Moreover, it is not known if increased apoptotic susceptibility of Tregs may contribute to an impaired immunosuppressive function in sarcoidosis. Therefore, the aim of this study is to analyze proportions, phenotype, survival, and apoptotic susceptibility of Tregs in sarcoidosis. METHODS: Patients with pulmonary sarcoidosis (n = 58) were included at time of diagnosis...
2015: Respiratory Research
P Geserick, J Wang, R Schilling, S Horn, P A Harris, J Bertin, P J Gough, M Feoktistova, M Leverkus
Acquired or intrinsic resistance to apoptotic and necroptotic stimuli is considered a major hindrance of therapeutic success in malignant melanoma. Inhibitor of apoptosis proteins (IAPs) are important regulators of apoptotic and necroptotic cell death mediated by numerous cell death signalling platforms. In this report we investigated the impact of IAPs for cell death regulation in malignant melanoma. Suppression of IAPs strongly sensitized a panel of melanoma cells to death ligand-induced cell death, which, surprisingly, was largely mediated by apoptosis, as it was completely rescued by addition of caspase inhibitors...
2015: Cell Death & Disease
F Bernassola, C Scheuerpflug, I Herr, P H Krammer, K-M Debatin, G Melino
No abstract text is available yet for this article.
September 2015: Cell Death and Differentiation
Á J De la Rosa, Á Rodríguez-Hernández, R González, S Romero-Brufau, E Navarro-Villarán, L Barrera-Pulido, S Pereira, L M Marín, F López-Bernal, J M Álamo, M A Gómez-Bravo, F J Padillo, J Muntané
Hepatocellular carcinoma develops in cirrhotic liver. The nitric oxide (NO) synthase type III (NOS-3) overexpression induces cell death in hepatoblastoma cells. The study developed gene therapy designed to specifically overexpress NOS-3 in cultured hepatoma cells, and in tumors derived from orthotopically implanted tumor cells in fibrotic livers. Liver fibrosis was induced by CCl4 administration in mice. The first-generation adenoviruses were designed to overexpress NOS-3 or green fluorescent protein, and luciferase complementary DNA under the regulation of murine alpha-fetoprotein (AFP) and Rous Sarcoma Virus (RSV) promoters, respectively...
January 2016: Gene Therapy
Sarika Daripally, Sateesh Reddy Nallapalle, Saritha Katta, Vidudala V T S Prasad
We investigated risk association of oral cancers (tongue and buccal mucosa cancers) with FAS (-1377G > A and FAS -670 A > G) and FASL (-844 T > C) SNPs, in males and females. A case-control study of 535 oral cancer and 525 control subjects was performed. SNPs were detected in the genomic DNA isolated from peripheral blood using PCR-RFLP. We report FASL -844 T > C SNPs increased risk for buccal mucosa cancer in females but not in males. On the other hand, FAS genotypes did not alter the risk of the cancers in both females and males...
September 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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