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Orna Gera, Efrat Shavit-Stein, Doron Bushi, Sagi Harnof, Marina Ben Shimon, Ronen Weiss, Valery Golderman, Amir Dori, Nicola Maggio, Kate Finegold, Joab Chapman
Thrombin and activated protein C (aPC) bound to the endothelial protein C receptor (EPCR) both activate protease-activated receptor 1 (PAR1) generating either harmful or protective signaling respectively. In the present study we examined the localization of PAR-1 and EPCR and thrombin activity in Schwann glial cells of normal and crushed peripheral nerve and in Schwannoma cell lines. In the sciatic crush model nerves were excised 1 hour, 1, 4, and 7 days after the injury. Schwannoma cell lines produced high levels of prothrombin which is converted to active thrombin and expressed both EPCR and PAR-1 which co-localized...
October 19, 2016: Neuroscience
Selorme Adukpo, Ben A Gyan, Michael F Ofori, Daniel Dodoo, Thirumalaisamy P Velavan, Christian G Meyer
BACKGROUND: Malaria elicits inflammatory responses, which, if not well regulated, may exert detrimental effects. When activated, triggering receptor expressed on myeloid cells (TREM)-1 enhances inflammatory responses by increasing secretion of IL-8 and other Th1 cytokines. In contrast, TREM-like transcript 1 (TREML-1) promotes anti-inflammatory responses by binding to TREM-1 ligands and competing with TREM-1, thus antagonizing TREM-1 activation to reduce inflammation. Endothelial protein C receptor (EPCR) also mediates anti-inflammatory responses by activating endothelial protein C (PC)...
September 27, 2016: Tropical Medicine & International Health: TM & IH
J M Zhu, M He, L Huang, Y L Su, L Li, M Li
Objective: To investigate the expression of endothelial protein C receptor(EPCR)and its roles in plasma and placenta of patients with early onset severe preeclampsia. Methods: Sixty cases of severe preeclampsia women who delivered in Xuzhou Maternity and Child Health Care Hospital from March 2014 to February 2016, were recruited, which included 30 cases with early onset severe preeclampsia(early onset group, gestational week <34 weeks)and 30 patients with late onset severe preeclampsia(late onset group, gestational week ≥34 weeks)...
September 25, 2016: Zhonghua Fu Chan Ke za Zhi
H Gock, K F E Lee, L Murray-Segal, T B Mysore, A J F d'Apice, E J Salvaris, P J Cowan
Islet transplantation can potentially cure type 1 diabetes mellitus, but it is limited by a shortage of human donors as well as by islet graft destruction by inflammatory and thrombotic mechanisms. A possible solution to these problems is to use genetically modified pig islets. Endothelial protein C receptor (EPCR) enhances protein C activation and regulates coagulation, inflammation, and apoptosis. We hypothesized that human EPCR (hEPCR) expression on donor islets would improve graft survival and function...
July 2016: Transplantation Proceedings
Ram Vinod Roy, Abdolreza Ardeshirylajimi, Peyman Dinarvand, Likui Yang, Alireza R Rezaie
Activation of PAR1 by activated protein C (APC) and thrombin elicits paradoxical cytoprotective and cytotoxic signaling responses in vascular endothelial cells through cleavage of the receptor at Arg-46 and Arg-41 protease recognition sites, respectively. It has been reported that unlike a disruptive G-protein mediated PAR1 signaling by thrombin, APC induces a protective β-arrestin-2 biased PAR1 signaling by unknown mechanisms. We hypothesize that the occupancy of endothelial protein C receptor (EPCR) by the Gla-domain of protein C/APC is responsible for the β-arrestin-2 biased PAR1 signaling independent of the protease cleavage site...
August 25, 2016: Blood
David G Kent, Brad J Dykstra, Connie J Eaves
Hematopoietic stem cells with long-term repopulating activity can now be routinely obtained at purities of 40% to 50% from suspensions of adult mouse bone marrow. Here we describe robust protocols for both their isolation as CD45(+) EPCR(+) CD150(+) CD48(-) (ESLAM) cells using multiparameter cell sorting and for tracking their clonal growth and differentiation activity in irradiated mice transplanted with single ESLAM cells. The simplicity of these procedures makes them attractive for characterizing the molecular and biological properties of individual hematopoietic stem cells with unprecedented power and precision...
2016: Current Protocols in Stem Cell Biology
Richard K D Ephraim, Kwame O Darkwah, Samuel A Sakyi, Mabel Ephraim, Enoch O Antoh, Prince Adoba
BACKGROUND: Acute kidney injury (AKI) affects 3-7 % of patients admitted to the hospital and approximately 25-30 % of patients in the intensive care unit. RIFLE, a newly developed international consensus classification for AKI, defines three grades of severity-class R (risk), I (injury) and F (failure). The aim of this study was to evaluate whether the RIFLE system of classification can detect the incidence of AKI using retrospective data of in-patients at the Effia-Nkwanta Regional Hospital...
2016: BMC Nephrology
Marion Avril, Maria Bernabeu, Maxwell Benjamin, Andrew Jay Brazier, Joseph D Smith
UNLABELLED: Intercellular adhesion molecule 1 (ICAM-1) and the endothelial protein C receptor (EPCR) are candidate receptors for the deadly complication cerebral malaria. However, it remains unclear if Plasmodium falciparum parasites with dual binding specificity are involved in cytoadhesion or different parasite subpopulations bind in brain microvessels. Here, we investigated this issue by studying different subtypes of ICAM-1-binding parasite lines. We show that two parasite lines expressing domain cassette 13 (DC13) of the P...
2016: MBio
Jakob S Jespersen, Christian W Wang, Sixbert I Mkumbaye, Daniel Tr Minja, Bent Petersen, Louise Turner, Jens Ev Petersen, John Pa Lusingu, Thor G Theander, Thomas Lavstsen
Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding human endothelial protein C receptor (EPCR) through the CIDRα1 domain of certain PfEMP1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR-binding CIDRα1 domains epitomize PfEMP1 expressed in severe malaria...
2016: EMBO Molecular Medicine
Estela Shabani, Robert O Opoka, Paul Bangirana, Gregory S Park, Gregory M Vercellotti, Weihua Guan, James S Hodges, Thomas Lavstsen, Chandy C John
The endothelial protein C receptor (EPCR) appears to play an important role in Plasmodium falciparum endothelial cell binding in severe malaria (SM). Despite consistent findings of elevated soluble EPCR (sEPCR) in other infectious diseases, field studies to date have provided conflicting data about the role of EPCR in SM. To better define this role, we performed genotyping for the rs867186-G variant, associated with increased sEPCR levels, and measured sEPCR levels in two prospective studies of Ugandan children designed to understand immunologic and genetic factors associated with neurocognitive deficits in SM including 551 SM children, 71 uncomplicated malaria (UM) and 172 healthy community children (CC)...
2016: Scientific Reports
Caroline Pehrson, Line Mathiesen, Kristine K Heno, Ali Salanti, Mafalda Resende, Ron Dzikowski, Peter Damm, Stefan R Hansson, Christopher L King, Henning Schneider, Christian W Wang, Thomas Lavstsen, Thor G Theander, Lisbeth E Knudsen, Morten A Nielsen
BACKGROUND: Placental malaria occurs when Plasmodium falciparum infected erythrocytes sequester in the placenta. Placental parasite isolates bind to chondroitin sulphate A (CSA) by expression of VAR2CSA on the surface of infected erythrocytes, but may sequester by other VAR2CSA mediated mechanisms, such as binding to immunoglobulins. Furthermore, other parasite antigens have been associated with placental malaria. These findings have important implications for placental malaria vaccine design...
2016: Malaria Journal
Hyejin Kang, Taeho Lee, Jong-Sup Bae
Beyond its role in the activation of protein C, the endothelial cell protein C receptor (EPCR) plays an important role in the cytoprotective pathway. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-[Formula: see text] converting enzyme (TACE). Pelargonidin is a well-known red pigment found in plants, and has been reported to have important biological activities that are potentially beneficial to human health. However, little is known about the effects of pelargonidin on EPCR shedding...
2016: American Journal of Chinese Medicine
Laurent O Mosnier, Thomas Lavstsen
Of the five Plasmodium species that infect humans, infection with P. falciparum is the most lethal, causing severe malaria syndromes, that result in over half a million annual deaths. With parasites becoming increasingly resistant to artemisinin there is an urgent need for new preventative and therapeutic options, for which understanding of the mechanisms that cause death and disability in malaria is essential. The recent discoveries that certain variants of P. falciparum erythrocyte membrane protein 1 (PfEMP1) expressed on infected erythrocytes are intimately linked to the precipitation of severe malaria syndromes and that these PfEMP1 variants contain EPCR binding domains provides new opportunities to improve our understanding of the molecular mechanisms responsible for the pathogenesis of severe malaria...
May 2016: Thrombosis Research
Maria Bernabeu, Samuel A Danziger, Marion Avril, Marina Vaz, Prasad H Babar, Andrew J Brazier, Thurston Herricks, Jennifer N Maki, Ligia Pereira, Anjali Mascarenhas, Edwin Gomes, Laura Chery, John D Aitchison, Pradipsinh K Rathod, Joseph D Smith
The interplay between cellular and molecular determinants that lead to severe malaria in adults is unexplored. Here, we analyzed parasite virulence factors in an infected adult population in India and investigated whether severe malaria isolates impair endothelial protein C receptor (EPCR), a protein involved in coagulation and endothelial barrier permeability. Severe malaria isolates overexpressed specific members of the Plasmodium falciparum var gene/PfEMP1 (P. falciparum erythrocyte membrane protein 1) family that bind EPCR, including DC8 var genes that have previously been linked to severe pediatric malaria...
June 7, 2016: Proceedings of the National Academy of Sciences of the United States of America
S Besbes, R Attal, S Mirshahi, J Chidiac, I Mahé, M Pocard, J Soria, M Mirshahi
INTRODUCTION: The microparticles (MPs) are sized vesicles of less than 1 μm, from different cell types upon activation or subsequent to apoptosis. They are involved in the thrombotic process, particularly in cancer. The role of MPs in ovarian cancer and their involvement in thrombosis being poorly understood. AIM: The aim of this study was to identify in vitro the generation of MPs by an human ovarian adenocarcinoma cell line (OVCAR-3). MATERIALS AND METHODS: OVCAR-3 cells were cultured in three conditions [without stimulation, with protein C (PC), and with activated protein C (APC)]...
April 2016: Thrombosis Research
M Zarfati, T Katz, I Avivi, B Brenner, A Aharon
INTRODUCTION: Multiple myeloma (MM) is an incurable, genetically heterogeneous malignancy of plasma cells that secrete non-functioning immunoglobulins and present high proteasome activity. MM is characterized by bone marrow infiltration leading to multiple lytic bone lesions, cytopenia and increased rate of thrombotic events. Microvesicles (MVs) include exosomes (30-100 nm) and microparticles (0.1-1 micron) shed from various cells and expressing antigens reflecting their cellular origin...
April 2016: Thrombosis Research
F Martin, J C Long, S A O'Toole, J J O'Leary, F Abu Saadeh, N Gleeson, L A Norris
INTRODUCTION: The close relationship between coagulation, thrombosis and cancer has long been established. Gynaecological cancers, in particular ovarian cancers, carry a high risk of thrombosis but coagulation activation is also thought to play a role in tumorigenesis and metastasis. In experimental animal models of metastasis, mice with a genetic procoagulant phenotype are prone to develop metastasis and anticoagulant therapy dramatically reduces pulmonary metastasis in these models...
April 2016: Thrombosis Research
Shiri Gur-Cohen, Tomer Itkin, Sagarika Chakrabarty, Claudine Graf, Orit Kollet, Aya Ludin, Karin Golan, Alexander Kalinkovich, Guy Ledergor, Eitan Wong, Elisabeth Niemeyer, Ziv Porat, Ayelet Erez, Irit Sagi, Charles T Esmon, Wolfram Ruf, Tsvee Lapidot
No abstract text is available yet for this article.
April 2016: Nature Medicine
Wonhwa Lee, Sae-Kwang Ku, Hyukjae Choi, Jong-Sup Bae
Diketopiperazine is a natural products found from bacteria, fungi, marine sponges, gorgonian and red algae. They are cyclic dipeptides possessing relatively simple and rigid structures with chiral nature and various side chains. The compounds in this structure class have been known to possess diverse bioactivities including antibiotic activity, anti-cancer activity, neuroprotective activity, and anti-inflammatory activity. The endothelial cell protein C receptor (EPCR) plays an important role in the cytoprotective pathway and in the activation of protein C...
April 2016: Fitoterapia
S Guillou, S Tamareille, S Giraud, G Poitevin, D Prunier-Mirebeau, P Nguyen, F Prunier, L Macchi
INTRODUCTION: Fondaparinux (FDX) was demonstrated to be cardioprotective in a rat model of myocardial ischemia reperfusion. In this model, FDX reduced infarct size after 2h of reperfusion, involving the activation of the survivor activating factor enhancement (SAFE) pathway as early as 30min post-reperfusion. Our aim was to study if this cardioprotection could be explained by anti-inflammatory mechanisms and a protective effect on vessels. METHODS: Wistar male rats were subjected to 40minutes (min) of myocardial ischemia, followed by 30min or 2h of reperfusion...
May 2016: Thrombosis Research
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