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https://www.readbyqxmd.com/read/28819186/cd24-induces-changes-to-the-surface-receptors-of-b-cell-microvesicles-with-variable-effects-on-their-rna-and-protein-cargo
#1
D Craig Ayre, Ian C Chute, Andrew P Joy, David A Barnett, Andrew M Hogan, Marc P Grüll, Lourdes Peña-Castillo, Andrew S Lang, Stephen M Lewis, Sherri L Christian
The CD24 cell surface receptor promotes apoptosis in developing B cells, and we recently found that it induces B cells to release plasma membrane-derived, CD24-bearing microvesicles (MVs). Here we have performed a systematic characterization of B cell MVs released from WEHI-231 B lymphoma cells in response to CD24 stimulation. We found that B cells constitutively release MVs of approximately 120 nm, and that CD24 induces an increase in phosphatidylserine-positive MV release. RNA cargo is predominantly comprised of 5S rRNA, regardless of stimulation; however, CD24 causes a decrease in the incorporation of protein coding transcripts...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28815218/capturing-the-systemic-immune-signature-of-a-norovirus-infection-an-n-of-1-case-study-within-a-clinical-trial
#2
Antony J Cutler, Joao Oliveira, Ricardo C Ferreira, Ben Challis, Neil M Walker, Sarah Caddy, Jia Lu, Helen E Stevens, Deborah J Smyth, Marcin L Pekalski, Jane Kennet, Kara M D Hunter, Ian Goodfellow, Linda S Wicker, John A Todd, Frank Waldron-Lynch
BACKGROUND:  The infection of a participant with norovirus during the adaptive study of interleukin-2 dose on regulatory T cells in type 1 diabetes (DILT1D) allowed a detailed insight into the cellular and cytokine immune responses to this prevalent gastrointestinal pathogen. METHODS:  Serial blood, serum and peripheral blood mononuclear cell (PBMC) samples were collected pre-, and post-development of the infection. To differentiate between the immune response to norovirus and to control for the administration of a single dose of aldesleukin (recombinant interleukin-2, rIL-2) alone, samples from five non-infected participants administered similar doses were analysed in parallel...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28810810/reduced-expression-of-siglec-7-nkg2a-and-cd57-on-terminally-differentiated-cd56-cd16-nk-cell-subset-is-associated-with-nk-cell-dysfunction-in-chronic-hiv-1-clade-c-infection
#3
Michael Zulu, Kewreshini Naidoo, Zenele Mncube, Manjeetha Jaggernath, Philip Jr Goulder, Thumbi Ndung'u, Marcus Altfeld, Christina Fanesa Thobakgale
BACKGROUND: HIV-1 viremia has been shown to induce several phenotypic and functional abnormalities in natural killer (NK) cells. To assess immune defects associated with HIV viremia, we examined NK cell function, differentiation status and phenotypic alterations based on expression of inhibitory and activating receptors on NK cells in HIV-1 subtype C chronically infected participants from Durban, South Africa. METHODS: NK cell phenotypic profiles were characterized by assessing Siglec-7, NKG2A and NKG2C markers on frozen peripheral blood mononuclear cells (PBMCs) from viremic, antiretroviral therapy (ART)-naïve HIV-1 chronically infected participants (n=23), HIV-1 chronically infected participants who have been on combination antiretroviral therapy (cART) for at least 12 months (n=23) compared to healthy donors (n=23)...
August 16, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28791015/influence-of-irradiated-peripheral-blood-mononuclear-cells-on-both-ex-vivo-proliferation-of-human-natural-killer-cells-and-change-in-cellular-property
#4
María Delso-Vallejo, Jutta Kollet, Ulrike Koehl, Volker Huppert
Clinical studies with adoptive immunotherapy using allogeneic natural killer (NK) cells showed feasibility, but also limitation regarding the transfused absolute cell numbers. First promising results with peripheral blood mononuclear cells (PBMCs) as feeder cells to improve the final cell number need further optimization and investigation of the unknown controlling mechanism in the cross-talk to NK cells. We investigated the influence of irradiated autologous PBMCs to boost NK cell proliferation in the presence of OKT3 and IL-2...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28757612/the-cd24-siglec-g-axis-protects-mice-against-cuprizone-induced-oligodendrocyte-loss-targeting-danger-signal-for-neuroprotection
#5
Ning Li, Pan Zheng, Yang Liu
No abstract text is available yet for this article.
July 31, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28755952/are-humans-prone-to-autoimmunity-implications-from-evolutionary-changes-in-hominin-sialic-acid-biology
#6
REVIEW
Ajit Varki
Given varied intrinsic and extrinsic challenges to the immune system, it is unsurprising that each evolutionary lineage evolves distinctive features of immunoreactivity, and that tolerance mechanisms fail, allowing autoimmunity. Humans appear prone to many autoimmune diseases, with mechanisms both genetic and environmental. Another rapidly evolving biological system involves sialic acids, a family of monosaccharides that are terminal caps on cell surface and secreted molecules of vertebrates, and play multifarious roles in immunity...
July 26, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28751214/glycan-profiling-analysis-using-evanescent-field-fluorescence-assisted-lectin-array-importance-of-sugar-recognition-for-cellular-uptake-of-exosomes-from-mesenchymal-stem-cells
#7
Asako Shimoda, Yoshiro Tahara, Shin-Ichi Sawada, Yoshihiro Sasaki, Kazunari Akiyoshi
Studies involving the functional analysis of exosomal contents including proteins, DNA, and RNA have been reported. Most membrane proteins and lipids are glycosylated, which controls their physical properties and functions, but little is known about glycans on exosomes owing to the difficulty of analysing them. To shed light on these issues, we collected exosomes from mesenchymal stem cells (MSCs) derived from human adipose tissue for glycan profiling using evanescent-field fluorescence-assisted lectin array as well as analysis of their uptake in vivo...
July 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28747436/the-alzheimer-s-disease-protective-cd33-splice-variant-mediates-adaptive-loss-of-function-via-diversion-to-an-intracellular-pool
#8
Shoib S Siddiqui, Stevan A Springer, Andrea Verhagen, Venkatasubramaniam Sundaramurthy, Frederico Alisson-Silva, Weiping Jiang, Pradipta Ghosh, Ajit Varki
The immunomodulatory receptor Siglec-3/CD33 influences risk for late-onset Alzheimers disease (LOAD), an apparently human-specific post-reproductive disease. CD33 generates two splice variants: a full-length CD33M transcript produced primarily by the LOAD-risk allele and a shorter CD33m isoform lacking the sialic acid-binding domain, produced primarily from the LOAD-protective allele. A SNP that modulates CD33 splicing to favor CD33m is associated with enhanced microglial activity. Individuals expressing more protective isoform accumulate less brain Beta-amyloid and have a lower LOAD risk...
July 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28742001/molecular-cloning-of-porcine-siglec-3-siglec-5-and-siglec-10-and-identification-of-siglec-10-as-an-alternative-receptor-for-porcine-reproductive-and-respiratory-syndrome-virus-prrsv
#9
Jiexiong Xie, Isaura Christiaens, Bo Yang, Wander Van Breedam, Tingting Cui, Hans J Nauwynck
In recent years, several entry mediators have been characterized for porcine reproductive and respiratory syndrome virus (PRRSV). Porcine sialoadhesin [pSn, also known as sialic acid-binding immunoglobulin-type lectin (Siglec-1)] and porcine CD163 (pCD163) have been identified as the most important host entry mediators that can fully coordinate PRRSV infection into macrophages. However, recent isolates have not only shown a tropism for sialoadhesin-positive cells, but also for sialoadhesin-negative cells. This observation might be partly explained by the existence of additional receptors that can support PRRSV binding and entry...
July 26, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28734845/leveraging-siglec-8-endocytic-mechanisms-to-kill-human-eosinophils-and-malignant-mast-cells
#10
Jeremy A O'Sullivan, Daniela J Carroll, Yun Cao, Adriano N Salicru, Bruce S Bochner
BACKGROUND: Sialic acid-binding immunoglobulin-like lectin (Siglec)-8 is a cell-surface protein expressed selectively on human eosinophils, mast cells, and basophils, making it an ideal target for the treatment of diseases involving these cell types. However, the effective delivery of therapeutic agents to these cells requires an understanding of the dynamics of Siglec-8 surface expression. OBJECTIVES: We sought to determine whether Siglec-8 is endocytosed in human eosinophils and malignant mast cells, identify mechanisms underlying its endocytosis, and demonstrate whether a toxin can be targeted to Siglec-8-bearing cells to kill these cells...
July 20, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28724800/siglec-g-represses-damp-mediated-effects-on-t-cells
#11
Tomomi Toubai, Corinne Rossi, Katherine Oravecz-Wilson, Cynthia Zajac, Chen Liu, Thomas Braun, Hideaki Fujiwara, Julia Wu, Yaping Sun, Stuart Brabbs, Hiroya Tamaki, John Magenau, Pang Zheng, Yang Liu, Pavan Reddy
The role of negative regulators or suppressors of the damage-associated molecular pattern-mediated (DAMP-mediated) stimulation of innate immune responses is being increasingly appreciated. However, the presence and function of suppressors of DAMP-mediated effects on T cells, and whether they can be targeted to mitigate T cell-dependent immunopathology remain unknown. Sialic acid-binding immunoglobulin-like lectin G (Siglec-G) is a negative regulator of DAMP-mediated responses in innate immune cells, but its T cell-autonomous role is unknown...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28680750/il-33-restricts-tumor-growth-and-inhibits-pulmonary-metastasis-in-melanoma-bearing-mice-through-eosinophils
#12
Valeria Lucarini, Giovanna Ziccheddu, Iole Macchia, Valentina La Sorsa, Francesca Peschiaroli, Carla Buccione, Antonella Sistigu, Massimo Sanchez, Sara Andreone, Maria Teresa D'Urso, Massimo Spada, Daniele Macchia, Claudia Afferni, Fabrizio Mattei, Giovanna Schiavoni
The alarmin IL-33 is an IL-1 family member that stimulates pleiotropic immune reactions depending on the target tissue and microenvironmental factors. In this study, we have investigated the role of IL-33/ST2 axis in antitumor response to melanoma. Injection of IL-33 in mice-bearing subcutaneous B16.F10 melanoma resulted in significant tumor growth delay. This effect was associated with intratumoral accumulation of CD8(+) T cells and eosinophils, decrease of immunosuppressive myeloid cells, and a mixed Th1/Th2 cytokine expression pattern with local and systemic activation of CD8(+) T and NK cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28672935/next-generation-sequencing-reveals-lymph-node-metastasis-associated-genetic-markers-in-colorectal-cancer
#13
Ni Xie, Yujiang Yao, Lili Wan, Ting Zhu, Litao Liu, Jianhui Yuan
Colorectal cancer is the third most prevalent type of cancer in the United States. Early diagnosis of lymph node metastases is essential to improve the prognosis for patients with colorectal cancer. Therefore, the present study aimed to screen genetic markers, including single nucleotide polymorphisms (SNPs), copy number variations (CNVs) and mRNA expression, associated with lymph node metastases in patients with colorectal cancer to enable an early diagnosis. Targeted next-generation sequencing was applied to capture SNPs and CNVs in tumor-related candidate genes within tumor tissues from 39 colorectal cancer patients; reverse transcription-quantitative polymerase chain reaction was used to detect the specific mRNA level of tumor-related candidate genes, including vascular endothelial growth factor C, cyclin-A2, Interleukin-2, ATP-binding cassette sub-family G member 2, epidermal growth factor (EGF) and nuclear factor kappa B subunit 1 (NFKB1) on chromosome 4...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28671693/transcriptomic-analysis-of-purified-human-cortical-microglia-reveals-age-associated-changes
#14
Thais F Galatro, Inge R Holtman, Antonio M Lerario, Ilia D Vainchtein, Nieske Brouwer, Paula R Sola, Mariana M Veras, Tulio F Pereira, Renata E P Leite, Thomas Möller, Paul D Wes, Mari C Sogayar, Jon D Laman, Wilfred den Dunnen, Carlos A Pasqualucci, Sueli M Oba-Shinjo, Erik W G M Boddeke, Suely K N Marie, Bart J L Eggen
Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes CX3CR1, P2RY12 and ITGAM (CD11B). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including TLR, Fcγ and SIGLEC receptors, as well as TAL1 and IFI16, regulators of proliferation and cell cycle...
August 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28619634/enhancement-of-siglec-8-expression-predicts-adverse-prognosis-in-patients-with-clear-cell-renal-cell-carcinoma
#15
Chenzhang Ou, Li Liu, Jiajun Wang, Siyuan Dai, Yang Qu, Ying Xiong, Wei Xi, Jiejie Xu, Jianming Guo
PURPOSE: Sialic acid-binding immunoglobulin-like lectins (siglecs) family has important functions in tumor progression. The purpose of our study is to figure out the correlation between the expression level of Siglec-8 and prognosis of patients with clear cell renal cell carcinoma (ccRCC), and then to predict the overall survival (OS) via a novel nomogram. MATERIALS AND METHODS: A group of patients (n = 267) histologically diagnosed with ccRCC from Zhongshan Hospital were included into our study...
June 12, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28608355/-neuronal-glycolipids-regulate-glial-cell-division-negatively-during-development-and-following-a-lesion
#16
REVIEW
M Nieto-Sampedro, V C Muneton-Gomez
Glial cells in the central nervous system of adult mammals outnumber neurons 10-fold. Their number remains stationary throughout adulthood, controlled by the concomitant presence of mitogens and mitogen inhibitors. The most abundant inhibitor, neurostatin, is ganglioside GD1b O-acetylated on hydroxyl 9 of its outermost sialic acid. Neurostatin inhibited the proliferation of primary microglia and astroblasts in culture (cytostatic) as well as both rodent and human glioma cells (cytotoxic) at nanomolar concentrations...
June 16, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28556976/exploring-the-radiosynthesis-and-in-vitro-characteristics-of-68-ga-ga-dota-siglec-9
#17
Svend B Jensen, Meeri Käkelä, Lars Jødal, Olli Moisio, Aage K O Alstrup, Sirpa Jalkanen, Anne Roivainen
Vascular adhesion protein 1 is a leukocyte homing-associated glycoprotein, which upon inflammation rapidly translocates from intracellular sources to the endothelial cell surface. It has been discovered that the cyclic peptide residues 283-297 of sialic acid-binding IgG-like lectin 9 (Siglec-9) "CARLSLSWRGLTLCPSK" bind to vascular adhesion protein 1 and hence makes the radioactive analogues of this compound ([(68) Ga]Ga-DOTA-Siglec-9) interesting as a noninvasive visualizing marker of inflammation. Three different approaches to the radiosynthesis of [(68) Ga]Ga-DOTA-Siglec-9 are presented and compared with previously published methods...
May 30, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28465620/ivig-regulates-the-survival-of-human-but-not-mouse-neutrophils
#18
Christoph Schneider, Simone Wicki, Stefanie Graeter, Tankica M Timcheva, Christian W Keller, Isaak Quast, Danila Leontyev, Iglika K Djoumerska-Alexieva, Fabian Käsermann, Stephan M Jakob, Petya A Dimitrova, Donald R Branch, Richard D Cummings, Jan D Lünemann, Thomas Kaufmann, Hans-Uwe Simon, Stephan von Gunten
Intravenous immunoglobulin (IVIG) are purified IgG preparations made from the pooled plasma from thousands of healthy donors and are being tested in preclinical mouse models. Inherent challenges, however, are the pluripotency of IVIG and its xenogeneicity in animals. IVIG can alter the viability of human neutrophils via agonistic antibodies to Fas and Siglec-9. In this study, we compared the effects of IVIG on human and mouse neutrophils using different death assays. Different commercial IVIG preparations similarly induced cytokine-dependent death in human neutrophils, whereas they had no effects on the survival of either peripheral blood or bone marrow neutrophils from C57BL/6 or BALB/c mice...
May 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28454648/the-siglec14-null-allele-is-associated-with-mycobacterium-tuberculosis-and-bcg-induced-clinical-and-immunologic-outcomes
#19
Andrew D Graustein, David J Horne, Jerry J Fong, Flavio Schwarz, Heather C Mefford, Glenna J Peterson, Richard D Wells, Munyaradzi Musvosvi, Muki Shey, Willem A Hanekom, Mark Hatherill, Thomas J Scriba, Nguyen Thuy Thuong Thuong, Nguyen Thi Hoang Mai, Maxine Caws, Nguyen Duc Bang, Sarah J Dunstan, Guy E Thwaites, Ajit Varki, Takashi Angata, Thomas R Hawn
Humans exposed to Mycobacterium tuberculosis (Mtb) have variable susceptibility to tuberculosis (TB) and its outcomes. Siglec-5 and Siglec-14 are members of the sialic-acid binding lectin family that regulate immune responses to pathogens through inhibitory (Siglec-5) and activating (Siglec-14) domains. The SIGLEC14 coding sequence is deleted in a high proportion of individuals, placing a SIGLEC5-like gene under the expression of the SIGLEC14 promoter (the SIGLEC14 null allele) and causing expression of a Siglec-5 like protein in monocytes and macrophages...
May 2017: Tuberculosis
https://www.readbyqxmd.com/read/28416510/erythrocyte-sialoglycoproteins-engage-siglec-9-on-neutrophils-to-suppress-activation
#20
Anel Lizcano, Ismael Secundino, Simon Döhrmann, Ross Corriden, Cristina Rohena, Sandra Diaz, Pradipta Ghosh, Lingquan Deng, Victor Nizet, Ajit Varki
Healthy blood neutrophils are functionally quiescent in the bloodstream, have a short lifespan, and exit the circulation to carry out innate immune functions, or undergo rapid apoptosis and macrophage-mediated clearance to mitigate host tissue damage. Limitation of unnecessary intravascular neutrophil activation is also important to prevent serious inflammatory pathologies. Because neutrophils become easily activated after purification, we carried out ex vivo comparisons with neutrophils maintained in whole blood...
June 8, 2017: Blood
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