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Yu Huang, Zhiying Chen, Joon Hee Jang, Mirza S Baig, Grant Bertolet, Casey Schroeder, Shengjian Huang, Qian Hu, Yong Zhao, Dorothy E Lewis, Lidong Qin, Michael Xi Zhu, Dongfang Liu
BACKGROUND: Inhibitory receptor programmed cell death protein-1 (PD-1) is upregulated on a variety of immune cells, including natural killer (NK) cells, during chronic virus infection and tumorigenesis. Blockade of PD-1 or its ligands produces durable clinical responses with tolerable side effects in patients with a broad spectrum of cancers. However, the underlying molecular mechanisms of how PD-1 regulates NK cell function remain poorly characterized. OBJECTIVE: We sought to determine what effect PD-1 signaling has on NK cells...
April 18, 2018: Journal of Allergy and Clinical Immunology
Li Zhu, Mostafa Aly, Haihao Wang, Hristos Karakizlis, Rolf Weimer, Christian Morath, Ruben Jeremias Kuon, Bettina Toth, Naruemol Ekpoom, Gerhard Opelz, Volker Daniel
BACKGROUND: Patients with recurrent miscarriage (RM) show up-regulated cytotoxic NK cells that are suspected to play a causal role in abortion. In the present study, we investigated counter-regulating inhibitory mechanisms and compared the results in RM patients with those of healthy controls (HC), patients with end stage renal disease (ESRD) and kidney transplant recipients late post-transplant (TX). METHODS: NK, NKT and T cell subsets were analyzed in the peripheral blood of 31 RM, 14 female ESRD and 9 female TX patients as well as 21 female HC using eight-color fluorescence flow cytometry...
April 21, 2018: Clinical and Experimental Immunology
Christine Happle, Lena Meyer-Decking, Anika Dreier, Martin Wetzke, Stephanie Gläsener, Ruth Grychtol, Peter Braubach, Alexandra Jablonka, Sibylle Haid, Adan Chari Jirmo, Anika Habener, Jelena Skuljec, Gesine Hansen
PURPOSE: To study and isolate lung cells by flow cytometry, enzymatic digestion and generation of single cell suspensions is required. This significantly influences expression of cellular epitopes and protocols need to be adapted for the best isolation and subsequent analysis of specific cellular subsets. MATERIALS AND METHODS: We optimized protocols for the simultaneous isolation and characterization of specific human and murine lung cell types. For alveolar epithelial cells (AEC), a primarily dispase based digestion method and for leukocytes, a primarily collagenase based technique was adapted...
April 20, 2018: Experimental Lung Research
Christian Loftus, Mezida Saeed, Daniel M Davis, Iain E Dunlop
An emerging new paradigm is that immune cell activation is controlled by transient interactions between supramolecular assemblies of receptors and ligands. Current immunotherapy biologic pharmaceuticals that activate or desensitize NK cells are, however, individual molecules that do not replicate this nanoscale organization of proteins. Here, we use nanoscale graphene oxide (NGO) as a template to generate soluble nanoscale clusters of Natural Killer cell-activating antibodies. We control nanocluster size and molecular number to mimic reported values for cell surface proteins...
April 20, 2018: Nano Letters
Nadijane Valeria Ferreira da Mota, Milena Karina Colo Brunialti, Sidneia Sousa Santos, Flavia Ribeiro Machado, Murillo Assunçao, Luciano Cesar Pontes de Azevedo, Reinaldo Salomao
Monocytes and macrophages are pivotal in the host response to sepsis, recognizing the infecting microorganism and triggering an inflammatory response. These functions are, at least in part, modulated by the expression of cell surface receptors. We aimed to characterize the monocyte phenotype from septic patients during an ongoing sepsis process and its association with clinical outcomes. Sixty-one septic patients and 31 healthy volunteers (HVs) were enrolled in the study. Samples were obtained from patients at baseline (D0, N = 61), and after 7 (D7, N = 36) and 14 days of therapy (D14, N = 22)...
December 5, 2017: Shock
Qiao-Chu Wang, Liang Zhen
OBJECTIVE: To establish a novel method for ex vivo expansion of natural killer cells from human umbilical blood, so as to provide the basis for NK cell therapy. METHODS: Mononucleated cells from human umbilical blood were harvested and suspended in a serum-free medium containing 5% autologous plasma, recombinant human IL-15 (50 ng/ml) and hydrocortisone sodium succinate (5×10-8 mol/L) at a concentration of 1.5×106 /ml, then the cells were seeded into flasks pre-coated with heparin sodium (100 U/cm2 ) or/and anti-human CD16 antibody (1 µg/cm2 )...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Shi-Jian Huang, Hong-Min Yan, Zi-Kuan Guo
OBJECTIVE: To develop an easy method to amplify natural killer (NK) cells by using mononuclear cells in vitro, so as to lay the basis for NK cell therapy. METHODS: Umbilical cord blood from 3 healthy full-term pregnant women was collected, and the peripheral blood mononuclear cells (PBMNC) were harvested by density gradient centrifugation. Each sample of PBMNC was divided into 3 groups: CD16mAb, CD3 mAb and CD16mAb+CD3mAb- groups. The culture flasks were pre-coated with CD16, CD3 or CD3 plus CD16 mAb...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Junnan Xu, Lei Jiang, Hui Cao, Yufeng Jia, Shuo Wu, Cui Jiang, Tao Sun
Recombinant human thrombopoietin (rhTPO) is a key determinant of therapy for chemotherapy-induced thrombocytopenia (CIT) in patients with breast cancer. To assess the predictive value of preoperative inflammatory cells for response to rhTPO in breast cancer patients, a total of 198 female patients with breast cancer were enrolled between June 2011 and December 2016 in Liaoning Cancer Hospital. Peripheral blood samples before rhTPO therapy were obtained, the ratios of helper T cell (CD4+ ), cytotoxic T cell (CD8+ ), NK cell (CD16+ /CD56+ ), and B cell (CD19+ ) were analyzed, and CD4/CD8 ratios were calculated...
April 17, 2018: Journal of Interferon & Cytokine Research
Maria C Millan-Linares, Beatriz Bermudez, Maria E Martin, Ernesto Muñoz, Rocio Abia, Francisco Millan, Francisco J G Muriana, Sergio Montserrat-de la Paz
Grape (Vitis vinifera L.) seed has well-known potential for production of oil as a byproduct of winemaking and is a rich source of bioactive compounds. Herein, we report that the unsaponifiable fraction (UF) isolated from grape seed oil (GSO) possesses anti-oxidative and anti-inflammatory properties towards human primary monocytes. The UF isolated from GSO was phytochemically characterized by GC-MS and HPLC. Freshly obtained human monocytes were used to analyse the effects of GSOUF (10-100 μg mL-1) on oxidative and inflammatory responses using FACS analysis, RT-qPCR, and ELISA procedures...
April 17, 2018: Food & Function
Agnieszka Przemska-Kosicka, Caroline E Childs, Catherine Maidens, Honglin Dong, Susan Todd, Margot A Gosney, Kieran Michael Tuohy, Parveen Yaqoob
Natural killer (NK) cells are an important component of the immune response to influenza infection, but are subject to alteration during aging, which may play a role in impaired response to infection and vaccination in older people. Enhancement of NK cell activity could, therefore, present a means to improve the immune response to vaccination in older subjects, and pre- and probiotics offer an opportunity to modulate antiviral defenses via alteration of the gut microbiota. This study investigated the effect of a novel probiotic, Bifidobacterium longum bv...
2018: Frontiers in Immunology
Liqiang Liu, Xiangrong Liu, Rongliang Wang, Feng Yan, Yumin Luo, Ankush Chandra, Yuchuan Ding, Xunming Ji
Objectives The protective effects of hypothermia on acute stroke have been demonstrated in many studies. However, its underlying mechanisms have not been thoroughly elucidated. Following an ischemic stroke event, microglia undertakes an early 'healthy' M2 phenotype and gradually transform into a 'sick' M1 phenotype over time. This transformation of polarity of microglia has influence on the degree of damage following a stroke. This study investigated the effects of mild focal hypothermia on microglia polarization following ischemic stroke...
April 5, 2018: Neurological Research
Mari Asakura, Toshiyuki Tanaka, Kensuke Shoji, Shuhei Karakawa, Akira Ishiguro, Isao Miyairi
BACKGROUND: Suppurative cervical lymphadenitis is rare in children with limited information about the frequency of neutropenia in any series. METHODS: We conducted a retrospective review of pediatric patients in whom suppurative cervical lymphadenitis was diagnosed between April 2011 and March 2016 at a tertiary children's hospital in Tokyo, Japan. Microbiologically confirmed cases of cervical lymphadenitis with abscess formation were included in the analysis. RESULTS: Twenty-five patients (median age: 1 year old, 64% female) with abscess formation due to Staphylococcus aureus were identified...
April 2, 2018: Pediatric Infectious Disease Journal
Ayane Hori, Takashi Fujimura, Seiji Kawamoto
An intravenous injection of plasma-derived immunoglobulins is used for the treatment of severe infectious and autoimmune disorders. Despite of its clinical efficacy, precise mechanisms by which intravenous immunoglobulin (IVIg) suppresses proinflammatory immune response are still enigmatic. Here, we provide in vitro evidence that IVIg inhibits homeostatic proliferation of B cells accompanied by induction of their cell aggregation. The IVIg-driven suppression of B cell proliferation and induction of cell aggregation are both unaffected by treatment with a neutralizing antibody against low-affinity Fc receptors for IgG (CD16/FcγRIII and CD32/FcγRII), known cell surface ligands for IVIg...
April 2, 2018: Cytotechnology
Sunao Sugita, Kenichi Makabe, Yuko Iwasaki, Shota Fujii, Masayo Takahashi
Purpose: To determine whether human induced pluripotent stem (iPS) cell-derived retinal pigment epithelial (RPE) cells (iPS-RPE) can suppress natural killer (NK) cell activation. Methods: iPS-RPE cells were cocultured with peripheral blood mononuclear cells (PBMCs) or purified NK cells from healthy donors after stimulation with cytokines. To confirm expression of NK cell-specific markers, flow cytometry and quantitative RT-PCR (qRT-PCR) were performed. NK cells (or PBMCs) cocultured with iPS-RPE cells were assessed for proliferation by Ki-67 expression with flow cytometry, and NK suppression by RPE cells was assessed for granzyme B production with ELISA...
April 1, 2018: Investigative Ophthalmology & Visual Science
Andrea Cignarella, Serena Tedesco, Roberta Cappellari, Gian Paolo Fadini
The monocyte-macrophage cell lineage represents a major player in innate immunity, and is involved in many physiologic and pathologic conditions. Particularly, monocyte-macrophages play a very important role in atherosclerosis and cardiovascular disease. Monocyte heterogeneity is well recognized but the biologic and clinical meaning of the various monocyte subtypes is not entirely understood. Traditionally, monocytes can be divided in classical, intermediate, and nonclassical based on expression of the surface antigens CD14 and CD16...
March 30, 2018: Journal of Leukocyte Biology
Joshua A Welsh, Eleonora Scorletti, Geraldine F Clough, Nicola A Englyst, Christopher D Byrne
The enhanced liver fibrosis (LFS) score and the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) are algorithmic-derived scores for diagnosing severe (F3/F4) liver fibrosis. In a pilot, substudy of the Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy (WELCOME) trial, we tested whether measurements of plasma platelet-, endothelial-, and leukocyte-derived extracellular vesicles (EVs) counts are (a) associated with, and predict, F3/F4 fibrosis and (b) able to improve risk prediction of F3/F4 fibrosis in NAFLD, building upon LFS or NFS algorithms...
March 30, 2018: Journal of Leukocyte Biology
Lucas Ferrari de Andrade, Rong En Tay, Deng Pan, Adrienne M Luoma, Yoshinaga Ito, Soumya Badrinath, Daphne Tsoucas, Bettina Franz, Kenneth F May, Christopher J Harvey, Sebastian Kobold, Jason W Pyrdol, Charles Yoon, Guo-Cheng Yuan, F Stephen Hodi, Glenn Dranoff, Kai W Wucherpfennig
MICA and MICB are expressed by many human cancers as a result of cellular stress, and can tag cells for elimination by cytotoxic lymphocytes through natural killer group 2D (NKG2D) receptor activation. However, tumors evade this immune recognition pathway through proteolytic shedding of MICA and MICB proteins. We rationally designed antibodies targeting the MICA α3 domain, the site of proteolytic shedding, and found that these antibodies prevented loss of cell surface MICA and MICB by human cancer cells. These antibodies inhibited tumor growth in multiple fully immunocompetent mouse models and reduced human melanoma metastases in a humanized mouse model...
March 30, 2018: Science
Zhuoran Yin, Divya D Raj, Wandert Schaafsma, Roel A van der Heijden, Susanne M Kooistra, Aaffien C Reijne, Xiaoming Zhang, Jill Moser, Nieske Brouwer, Peter Heeringa, Chun-Xia Yi, Gertjan van Dijk, Jon D Laman, Erik W G M Boddeke, Bart J L Eggen
Rodent models of both aging and obesity are characterized by inflammation in specific brain regions, notably the corpus callosum, fornix, and hypothalamus. Microglia, the resident macrophages of the central nervous system, are important for brain development, neural support, and homeostasis. However, the effects of diet and lifestyle on microglia during aging are only partly understood. Here, we report alterations in microglia phenotype and functions in different brain regions of mice on a high-fat diet (HFD) or low-fat diet (LFD) during aging and in response to voluntary running wheel exercise...
2018: Frontiers in Molecular Neuroscience
Saori Maruo, Katsuhito Mori, Koka Motoyama, Miyuki Nakamura, Reina Kawarabayashi, Yoshinori Kakutani, Yuko Yamazaki, Tomoaki Morioka, Tetsuo Shoji, Masaaki Inaba, Masanori Emoto
BACKGROUND: Fetuin-A is a multifunctional circulating glycoprotein that can induce insulin resistance. Lately, adipose tissue has gained prominence as an effector site of fetuin-A. Although fetuin-A-induced proinflammatory polarization and migration of macrophages plays a crucial role, it remains obscure whether monocyte subsets in circulation could simulate characteristics of macrophages in adipose tissues. This study aims to investigate the correlation between monocyte subsets with fetuin-A and its relevant insulin resistance...
March 27, 2018: Clinical and Translational Medicine
Samira Hosseini, Fazel Shokri, Soheila Ansari Pour, Jalal Khoshnoodi, Mahmood Jeddi-Tehrani, Amir-Hassan Zarnani
Systemic monitoring of immune system may not precisely outline the local immune status in the uterus. This survey is a continuation of our previous studies on potential usefulness of menstrual blood (MB) immunophenotyping as a tool for investigation of immunological disturbances in pregnancy-related disorders. Peripheral blood (PB) and MB from healthy fertile (n = 15), unexplained recurrent spontaneous abortion (URSA; n = 15), and unexplained infertile women (n = 8) were collected simultaneously in the second day of their menstrual cycle and frequency of natural killer T (NKT)-like cell subpopulations were assessed by flow cytometry...
January 1, 2018: Reproductive Sciences
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