bluuebunny/crossref_metadata_2025_split huggingface dataset:
iC3b‐opsonized apoptotic cells mediate a distinct anti‐inflammatory response and transcriptional NF‐κB‐dependent blockade
Authors: Amarilyo Gil , Verbovetski Inna , Atallah Mizhir , Grau Amir , Wiser Giora , Gil Oranit , Ben‐Neriah Ynon , Mevorach Dror 
Published: December 2009

AbstractIn recent years, it has become apparent that the removal of apoptotic cells by macrophages and DC is not only noninflammatory, but also immune‐inhibitory, in most although not all circumstances. Complement may be involved in the uptake of apoptotic cells via direct binding of bridging factors in some physiological circumstances, by opsonization and engagement of the complement receptors. In the current study, we use a complement‐dependent system of apoptotic cell clearance by human‐derived macrophages and DC. Using a luciferase reporter gene and measuring immune response to non‐opsonic zymosan, we show that iC3b‐apoptotic cells induce NF‐κB inhibition in response to zymosan and LPS at the nuclear translocation, transcriptional and post‐transcriptional levels, leading to profound inhibition of proinflammatory cytokines. In addition, interaction with iC3b‐opsonized apoptotic cells is characterized by macrophage secretion of IL‐10 and lack of TGF‐β secretion. In conclusion, in cells with iC3b receptors, opsonized apoptotic cells mediate a distinct anti‐inflammatory response and transcriptional NF‐κB‐dependent blockage.
Functional analysis of the CD300e receptor in human monocytes and myeloid dendritic cells
Authors: Brckalo Tamara , Calzetti Federica , Pérez‐Cabezas Begoña , Borràs Francesc E. , Cassatella Marco A. , López‐Botet Miguel 
Published: December 2009

AbstractThe CD300e surface molecule, originally termed immune receptor expressed by myeloid cells (IREM)‐2, was reported to associate with the DNAX‐activating protein (DAP) 12 adaptor in co‐transfected cells, and is capable of signaling. In the present report, we investigated in detail the function of CD300e in monocytes and myeloid DC (mDC) freshly isolated from peripheral blood of normal blood donors. Upon engagement by an agonistic mAb, CD300e triggered an intracellular calcium mobilization and superoxide anion O production in monocytes. Activation via CD300e provided survival signals that prevented monocyte and mDC apoptosis, triggered the production of pro‐inflammatory cytokines and upregulated the expression of cell surface co‐stimulatory molecules in both cell types. Moreover, CD300e activation of mDC enhanced the alloreactive response of naive T cells. Overall, our data formally support the notion that CD300e functions as an activating receptor capable of regulating the innate immune response in myeloid cells.
In vivo depletion of CD4+FOXP3+ Treg cells by the PC61 anti‐CD25 monoclonal antibody is mediated by FcγRIII+ phagocytes
Authors: Setiady Yulius Y. , Coccia Jennifer A. , Park Peter U. 
Published: December 2009

AbstractDepletion of CD4+CD25+FoxP3+ Treg using PC61 mAb (anti‐murine CD25 rat IgG1) is widely used to characterize Treg function in vivo. However, the mechanism of Treg depletion remains largely unknown. Herein, we report the PC61 mAb's mechanism of action. In peripheral blood, a single injection of PC61 mAb eliminated ∼70% of CD4+FoxP3+ cells with the remaining Treg expressing low or no CD25. Functional blockade of Fcγ receptors with 2.4G2 mAb significantly inhibited PC61 mAb activity. Furthermore, Fcγ receptor (FcγR)III−/− mice were resistant to Treg depletion. FcγRIII is expressed on immune cells including NK cells and macrophages that are the major effector cells for Ab‐dependent‐cellular‐cytotoxicity and Ab‐dependent‐cellular‐phagocytosis, respectively. Depletion of NK cells had no effect, whereas depletion of phagocytes, including macrophages, by clodronate liposome significantly inhibited Treg depletion. Furthermore, in vitro, PC61 mAb can mediate Ab‐dependent‐cellular‐phagocytosis of CD25+ cells by WT or FcγRIIB−/−, but not FcγRIII−/−, macrophages. Altogether these data demonstrate the critical role of FcγRIII+ phagocytes in mediating Treg depletion by PC61 mAb. This finding may be useful in guiding the development of human Treg targeting therapy.
The effect of placental malaria infection on cord blood and maternal immunoregulatory responses at birth
Authors: Flanagan Katie L. , Halliday Alice , Burl Sarah , Landgraf Katja , Jagne Ya Jankey , Noho‐Konteh Fatou , Townend John , Miles David J. C. , van der Sande Marianne , Whittle Hilton , Rowland‐Jones Sarah 
Published: December 2009

AbstractPlacental malaria (PM), a frequent infection of pregnancy, provides an ideal opportunity to investigate the impact on immune development of exposure of the foetal immune system to foreign Ag. We investigated the effect of PM on the regulatory phenotype and function of cord blood cells from healthy Gambian newborns and peripheral blood cells from their mothers, and analyzed for effects on the balance between regulatory and effector responses. Using the gold standard for classifying PM we further distinguished between resolved infection and acute or chronic PM active at the time of delivery. We show that exposure to malarial Ag in utero results in the expansion of malaria‐specific FOXP3+ Treg and more generalized FOXP3+ CD4+ Treg in chronic and resolved PM, alongside increased Th1 pro‐inflammatory responses (IFN‐γ, TNF‐α, IFN‐γ:IL‐10) in resolved PM infection only. These observations demonstrate a clear effect of exposure to malarial Ag in foetal life on the immune environment at birth, with a regulatory response dominating in the newborns with ongoing chronic PM, while those with resolved infection produce both regulatory and inflammatory responses. The findings might explain some of the adverse effects on the health of babies born to women with PM.
Critical role of lipid rafts in CD154‐mediated T cell signaling
Authors: El Fakhry Youssef , Alturaihi Haydar , Diallo Djibril , Merhi Yehye , Mourad Walid 
Published: December 2009

AbstractAlthough signal pathways triggered via the CD40 molecule are well characterized, those induced via CD154 are less known. This study demonstrates that engagement of CD154 in Jurkat D1.1 cells with soluble CD40 leads to PKC α and δ activation, calcium mobilization, and phosphorylation of the Map kinases ERK1/2 and p38. Such response is accompanied by significant recruitment of CD154 into lipid rafts. Disruption of lipid rafts integrity with nystatin or methyl β‐cyclodextrin abrogated PKCα PKCδ and p38 phosphorylation, but had no effect on ERK1/2 phosphorylation. Inhibition of PKC activation completely abolished p38 phosphorylation but had no effect on ERK1/2 phosphorylation, suggesting that localization of CD154 within lipid rafts is an absolute requirement for CD154‐induced PKCα‐ and PKCδ‐dependent p38 phosphorylation. Furthermore, CD154 acts as co‐stimulator for the production of IL‐2 in an APC‐superantigen‐T‐cell activation model. The results obtained demonstrate for the first time, that lipid rafts are of immunological relevance for CD154‐triggered signals, and reinforce the importance of CD154 in T‐cell activation.
In vivo tumor cell rejection induced by NK cell inhibitory receptor blockade: Maintained tolerance to normal cells even in the presence of IL‐2
Authors: Vahlne Gustaf , Lindholm Katja , Meier Anders , Wickström Stina , Lakshmikanth Tadepally , Brennan Frank , Wilken Michael , Nielsen Rikke , Romagné François , Wagtmann Nicolai R. , Kärre Klas , Johansson Maria H. 
Published: December 2009

AbstractMissing‐self‐reactivity can be mimicked by blocking self‐specific inhibitory receptors on NK cells, leading to increased rejection of syngeneic tumor cells. Using a mouse model, we investigated whether Ab‐mediated blocking of inhibitory receptors, to a degree where NK cells rejected syngeneic tumor cells, would still allow self‐tolerance toward normal syngeneic cells. Ly49C/I inhibitory receptors on C57BL/6 (H‐2b) NK cells were blocked with F(ab')2 fragments of the mAb 5E6. Inhibitory receptor blockade in vivo caused rejection of i.v. inoculated fluorescence‐labeled syngeneic lymphoma line cells but not of syngeneic spleen cells, BM cells or lymphoblasts. The selective rejection of tumor cells was NK cell‐dependent and specifically induced by Ly49C/I blockade. Moreover, selective tumor rejection was maintained after treatment with 5E6 F(ab')2 for 9 wk, arguing against the induction of NK cell anergy or autoreactivity during this time. Combination therapy using 5E6 F(ab')2 together with high dose IL‐2 treatment further increased lymphoma cell rejection. In addition, combination therapy reduced growth of melanoma cell line tumors established by s.c. inoculation 3 days before start of treatment. Our results demonstrate that inhibitory receptor blockade does not result in attack on normal cells, despite potent reactivity against MHC class I‐expressing tumors.
DNA vaccination with T‐cell epitopes encoded within Ab molecules induces high‐avidity anti‐tumor CD8+ T cells
Authors: Pudney Victoria A. , Metheringham Rachael L. , Gunn Barbara , Spendlove Ian , Ramage Judith M. , Durrant Lindy G. 
Published: December 2009

AbstractStimulation of high‐avidity CTL responses is essential for effective anti‐tumor and anti‐viral vaccines. In this study we have demonstrated that a DNA vaccine incorporating CTL epitopes within an Ab molecule results in high‐avidity T‐cell responses to both foreign and self epitopes. The avidity and frequency was superior to peptide, peptide‐pulsed DC vaccines or a DNA vaccine incorporating the epitope within the native Ag. The DNA Ab vaccine was superior to an identical protein vaccine that can only cross‐present, indicating a role for direct presentation by the DNA vaccine. However, the avidity of CTL responses was significantly reduced in Fc receptor γ knockout mice or if the Fc region was removed suggesting that cross presentation of Ag via Fc receptor was also important in the induction of high‐avidity CTL. These results suggest that generation of high‐avidity CTL responses by the DNA vaccine is related to its ability to both directly present and cross‐present the epitope. High‐avidity responses were capable of efficient anti‐tumor activity in vitro and in vivo. This study demonstrates a vaccine strategy to generate high‐avidity CTL responses that can be used in anti‐tumor and anti‐viral vaccine settings.
S1P3 confers differential S1P‐induced migration by autoreactive and non‐autoreactive immature B cells and is required for normal B‐cell development
Authors: Donovan Erin E. , Pelanda Roberta , Torres Raul M. 
Published: December 2009

AbstractDuring B‐cell development, immature B‐cell fate is determined by whether the BCR is engaged in the bone marrow. Immature B cells that are non‐autoreactive continue maturation and emigrate from the marrow, whereas autoreactive immature B cells remain and are tolerized. However, the microenvironment where these events occur and the chemoattractants responsible for immature B‐cell trafficking within and out of the bone marrow remain largely undefined. Sphingosine 1‐phosphate (S1P) is a chemoattractant that directs lymphocyte trafficking and thymocyte egress and in this study we investigated whether S1P contributes to B‐cell development, egress and positioning within the bone marrow. Our findings show that immature B cells are chemotactic toward S1P but that this response is dependent on Ag receptor specificity: non‐autoreactive, but not autoreactive, immature B cells migrate toward S1P and are shown to require S1P3 receptor for this response. Despite this response, S1P3 is shown not to facilitate immature B‐cell egress but is required for normal B‐cell development including the positioning of transitional B cells within bone marrow sinusoids. These data indicate that S1P3 signaling directs immature B cells to a bone marrow microenvironment important for both tolerance induction and maturation.
Differential regulation of iron homeostasis during human macrophage polarized activation
Authors: Recalcati Stefania , Locati Massimo , Marini Agnese , Santambrogio Paolo , Zaninotto Federica , De Pizzol Maria , Zammataro Luca , Girelli Domenico , Cairo Gaetano 
Published: December 2009

AbstractIron metabolism in inflammation has been mostly characterized in macrophages exposed to pathogens or inflammatory conditions, mimicked by the combined action of LPS and IFN‐γ (M1 polarization). However, macrophages can undergo an alternative type of activation stimulated by Th2 cytokines, and acquire a role in cell growth and tissue repair control (M2 polarization). We characterized the expression of genes related to iron homeostasis in fully differentiated unpolarized (M0), M1 and M2 human macrophages. The molecular signature of the M1 macrophages showed changes in gene expression (ferroportin repression and H ferritin induction) that favour iron sequestration in the reticuloendothelial system, a hallmark of inflammatory disorders, whereas the M2 macrophages had an expression profile (ferroportin upregulation and the downregulation of H ferritin and heme oxygenase) that enhanced iron release. The conditioned media from M2 macrophages promoted cell proliferation more efficiently than those of M1 cells and the effect was blunted by iron chelation. The role of ferroportin‐mediated iron release was demonstrated by the absence of differences from the media of macrophages of a patient with loss of function ferroportin mutation. The distinct regulation of iron homeostasis in M2 macrophages provides insights into their role under pathophysiological conditions.
The A2aR adenosine receptor controls cytokine production in iNKT cells
Authors: Nowak Michael , Lynch Lydia , Yue Simon , Ohta Akio , Sitkovsky Michail , Balk Steven P. , Exley Mark. A. 
Published: December 2009

AbstractThe purine nucleoside adenosine is an important anti‐inflammatory molecule, inhibiting a variety of immune cells by adenosine receptor‐mediated mechanisms. Invariant NKT (iNKT) cells recognize glycolipids presented on CD1d molecules and produce vigorous amounts of cytokines upon activation, hence regulating immune reactions. The mechanisms polarizing their cytokine pattern are elusive. Previous studies demonstrated that adenosine can suppress IFN‐γ production by iNKT cells. We describe the expression of all four known adenosine receptors A1R, A2aR, A2bR and A3R on mouse iNKT cells. We show that IL‐4 production in primary mouse iNKT cells and a human iNKT line is efficiently inhibited by A2aR blockade with an inverse relation to IL‐4. These data are supported by A2aR‐deficient mice, which exhibit largely decreased levels of IL‐4, IL‐10 and TGF‐β concomitantly with an increase of IFN‐γ upon α‐galactosylceramide administration in vivo. While A2aR inhibits other lymphocyte populations, A2aR is required for the secretion of IL‐4 and IL‐10 by iNKT cells. These data suggest adenosine:A2aR‐mediated mechanisms can control the cytokine secretion pattern of iNKT cells.
Does TLR2 regulate intestinal inflammation?
Authors: Mowat Allan McI 
Published: December 2009

AbstractThere is almost no aspect of the immune response that is not regulated by TLR. Initially described as drivers of the innate immune response to pathogens, it is now clear that the TLR family can also influence most aspects of adaptive immunity, as well as determine how tissue cells interact with microbes in their environment. In particular, the intestine and its immune system must co‐exist with an enormous community of commensal bacteria and are also on constant alert against invading pathogens. Unsurprisingly, there is therefore great interest in how TLR might regulate physiological and pathological reactions in the gut. An article in this issue of the European Journal of Immunology addresses this question with some elegant experiments that indicate that TLR2 is not essential for the pathogenesis or T‐cell‐mediated regulation of different models of inflammatory bowel disease in mice.
Growing trend of CE at the omics level: The frontier of systems biology
Authors: Oh Eulsik , Hasan Md. Nabiul , Jamshed Muhammad , Park Soo Hyun , Hong Hye‐Min , Song Eun Joo , Yoo Young Sook 
Published: December 2009

AbstractIn a novel attempt to comprehend the complexity of life, systems biology has recently emerged as a state‐of‐the‐art approach for biological research in contrast to the reductionist approaches that have been used in molecular cell biology since the 1950s. Because a massive amount of information is required in many systems biology studies of life processes, we have increasingly come to depend on techniques that provide high‐throughput omics data. CE and CE coupled to MS have served as powerful analytical tools for providing qualitative and quantitative omics data. Recent systems biology studies have focused strongly on the diagnosis and treatment of diseases. The increasing number of clinical research papers on drug discovery and disease therapies reflects this growing interest among scientists. Since such clinical research reflects one of the ultimate purposes of bioscience, these trends will be sustained for a long time. Thus, this review mainly focuses on the application of CE and CE‐MS in diagnosis as well as on the latest CE methods developed. Furthermore, we outline the new challenges that arose in 2008 and later in elucidating the system‐level functions of the bioconstituents of living organisms.
Recent approaches for enhancing sensitivity in enantioseparations by CE
Authors: Sánchez‐Hernández Laura , García‐Ruiz Carmen , Luisa Marina María , Luis Crego Antonio 
Published: December 2009

AbstractThis article reviews the latest methodological and instrumental improvements for enhancing sensitivity in chiral analysis by CE. The review covers literature from March 2007 until May 2009, that is, the works published after the appearance of the latest review article on the same topic by Sánchez‐Hernández et al. [Electrophoresis 2008, 29, 237–251]. Off‐line and on‐line sample treatment techniques, on‐line sample preconcentration strategies based on electrophoretic and chromatographic principles, and alternative detection systems to the widely employed UV/Vis detection in CE are the most relevant approaches discussed for improving sensitivity. Microchip technologies are also included since they can open up great possibilities to achieve sensitive and fast enantiomeric separations.
Capillary and microchip electrophoresis in microdialysis: Recent applications
Authors: Guihen Elizabeth , O'Connor William T. 
Published: December 2009

AbstractThe theme of this review is to highlight the importance of microscale electrophoretic‐based separation systems in microdialysis (μD). The ability of CE and MCE to yield very rapid and highly efficient separations using just nanolitre volumes of microdialysate samples will also be discussed. Recent advances in this area will be highlighted, by illustration of some exciting new applications while the need for further innovation will be covered. The first section briefly introduces the concept of μD sampling coupled with electrophoresis‐based separation and the inherent advantages of this approach. The following section highlights some specific applications of CE separations in the detection of important biomarkers such as low‐molecular‐weight neurotransmitters, amino acids, and other molecules that are frequently encountered in μD. Various detection modes in CE are outlined and some of the advantages and drawbacks thereof are discussed. The last section introduces the concepts of micro‐total analysis systems and the coupling of MCE and μD. Some of the latest innovations will be illustrated. The concluding section reflects on the future of this important chemical alliance between μD and CE/MCE.
Recent developments in PDMS surface modification for microfluidic devices
Authors: Zhou Jinwen , Ellis Amanda Vera , Voelcker Nicolas Hans 
Published: December 2009

AbstractPDMS is enjoying continued and ever increasing popularity as the material of choice for microfluidic devices due to its low cost, ease of fabrication, oxygen permeability and optical transparency. However, PDMS's hydrophobicity and fast hydrophobic recovery after surface hydrophilization, attributed to its low glass transition temperature of less than −120°C, negatively impacts on the performance of PDMS‐based microfluidic device components. This issue has spawned a flurry of research to devise longer lasting surface modifications of PDMS, with particular emphasis on microfluidic applications. This review will present recent research on surface modifications of PDMS using techniques ranging from metal layer coatings and layer‐by‐layer depositions to dynamic surfactant treatments and the adsorption of amphipathic proteins. We will also discuss significant advances that have been made with a broad palette of gas‐phase processing methods including plasma processing, sol–gel coatings and chemical vapor deposition. Finally, we will present examples of applications and future prospects of modified PDMS surfaces in microfluidics, in areas such as molecular separations, cell culture in microchannels and biomolecular detection via immunoassays.
Electrophoretic and electrochromatographic separation of proteins in capillaries: An update covering 2007–2009
Authors: El Rassi Ziad 
Published: December 2009

AbstractThis review article covers 3‐year period from 2007 to 2009 and is a continuation of the review article by V. Dolnik, [Electrophoresis 2008, 29, 143–156]. This article with 125 references describes recent developments in CE and CEC of proteins in capillary format and does not cover the developments of CE and CEC in microchip format, since Tran et al. review the microchip subject in this special issue. The present review article has four major topics including (i) the separation media, (ii) multidimensional separations, (iii) detection, and (iv) applications.
Residual‐based variational multiscale methods for laminar, transitional and turbulent variable‐density flow at low Mach number
Authors: Gravemeier Volker , Wall Wolfgang A. 
Published: December 2009

AbstractIn the present study, residual‐based variational multiscale methods are developed for and applied to variable‐density flow at low Mach number. In particular, two different formulations are considered in this study: a standard stabilized formulation featuring SUPG/PSG/grad‐div terms and a complete residual‐based variational multiscale formulation additionally containing cross‐ and Reynolds‐stress terms as well as subgrid‐scale velocity terms in the energy‐conservation equation. The proposed methods are tested for various laminar flow test cases as well as a test case at laminar via transitional to turbulent flow stages. Stable and accurate results are obtained for all numerical examples. Substantial differences in the results between the two approaches do not become notable until a high temperature gradient is applied and the flow reaches a turbulent flow stage. The more pronounced influence of adding subgrid‐scale velocity terms to the energy‐conservation equation on the results than adding analogous terms to the momentum‐conservation equation in this situation appears particularly noteworthy. Copyright © 2009 John Wiley & Sons, Ltd.