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Shan Yu, Aaron D Pearson, Reyna K V Lim, David T Rodgers, Sijia Li, Holly B Parker, Meredith Weglarz, Eric N Hampton, Michael J Bollong, Jiayin Shen, Claudio Zambaldo, Danling Wang, Ashley K Woods, Timothy M Wright, Peter G Schultz, Stephanie A Kazane, Travis S Young, Matthew S Tremblay
Phosphodiesterase 4 (PDE4) inhibitors are approved for the treatment of some moderate to severe inflammatory conditions. However, dose-limiting side effects in the central nervous system and gastrointestinal tract, including nausea, emesis, headache, and diarrhea, have impeded the broader therapeutic application of PDE4 inhibitors. We sought to exploit the wealth of validation surrounding PDE4 inhibition by improving the therapeutic index through generation of an antibody-drug conjugate (ADC) that selectively targets immune cells through the CD11a antigen...
October 12, 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
Guido Wabnitz, Emre Balta, Yvonne Samstag
T-cells need to be tightly regulated during their activation and effector phase to assure an appropriate defence against cancer or pathogens and - vice versa - to avoid autoimmune reactions. Regulatory signals are provided via the immune synapse between T-cells and antigen-presenting cells (APCs) or target cells. The stability and kinetics of immune synapse formation is critical for proper T-cell functions. It requires dynamic rearrangements of the actin cytoskeleton necessary for organized spatio-temporal redistribution of receptors and adhesion molecules...
September 27, 2016: Advances in Biological Regulation
James T Thackeray, Jens P Bankstahl, Yong Wang, Kai C Wollert, Frank M Bengel
Acute tissue inflammation after myocardial infarction influences healing and remodeling and has been identified as a target for novel therapies. Molecular imaging holds promise for guidance of such therapies. The amino acid (11)C-methionine is a clinically approved agent which is thought to accumulate in macrophages, but not in healthy myocytes. We assessed the suitability of positron emission tomography (PET) with (11)C-methionine for imaging post-MI inflammation, from cell to mouse to man. Uptake assays demonstrated 7-fold higher (11)C-methionine uptake by polarized pro-inflammatory M1 macrophages over anti-inflammatory M2 subtypes (p<0...
2016: Theranostics
Anders G Kjaergaard, Anders Dige, Jeppe S Nielsen, Else Tønnesen, Jan Krog
Endothelial activation is pivotal in the development and escalation of sepsis. Central to endothelial activation is the endothelial up-regulation of cellular adhesion molecules (CAMs) including E-selectin, ICAM-1, VCAM-1, and PECAM-1. Shed CAMs are also found in circulating soluble forms (sCAMs). We investigated whether sCAMs can be used as biomarkers for the differentiation between septic and non-septic patients. Furthermore, we investigated lymphocyte and monocyte expression of LFA-1 (CD11a/CD18) and VLA-4 (CD49d/CD29) ligands for ICAM-1 and VCAM-1, respectively...
October 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
Álvaro Cobo-Calvo, Agnes Figueras, Laura Bau, Elisabet Matas, María Alba Mañé Martínez, Isabel León, Carles Majòs, Lucia Romero-Pinel, Sergio Martínez-Yélamos
Cell-adhesion molecules (CAMs) dynamics in Multiple Sclerosis (MS) patients have been widely studied after Natalizumab (NTZ) introduction. However, their temporal dynamics after NTZ withdrawal (NTZ-W) has not been described. We prospectively evaluate changes in the expression levels of CAMs (CD49d, CD29, L-Selectin and CD11a) involved in T cell migration of 22 MS patients after NTZ-W. CD49d, CD29 and CD11a expression experienced a continuous increase expression two months after NTZ-W and Cd49d expression at month six after NTZ-W correlated to NTZ treatment duration, both in CD45(+)CD4(+) and CD45(+)CD8(+)...
October 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Xavier Delabranche, Laure Stiel, François Severac, Anne-Cécile Galoisy, Laurent Mauvieux, Fatiha Zobairi, Thierry Lavigne, Florence Toti, Eduardo Anglès-Cano, Ferhat Meziani, Julie Boisramé-Helms
INTRODUCTION: Neutrophils extracellular traps (NETs) have recently emerged as a new potential link between inflammation, immunity and thrombosis and could play a key role in septic shock-induced disseminated intravascular coagulation (DIC) pathogenesis. The objective of our study was to investigate a potential link between NETosis and septic-shock induced DIC. METHODS: Twenty patients with septic shock (10 without and 10 with DIC according to JAAM 2006 score) were prospectively included in our study...
August 2, 2016: Shock
Maria Raquel Cosate, Gabriela Hase Siqueira, Gisele Oliveira de Souza, Silvio Arruda Vasconcellos, Ana Lucia T O Nascimento
A severe re-emergingzoonosis, leptospirosis, is caused by pathogenic spirochetes of the genus Leptospira. Several studies have identified leptospiral surface proteins with the ability to bind ECM and plasma components, which could mediate adhesion and invasion through the hosts. It has been shown that Mce of pathogenic Leptospira spp. is an RGD (Arg-Gly-Asp)-motif-dependent virulence factor, responsible for infection of cells and animals. In the present article, we decided to further study the repertoire of the Mce activities in leptospiral biological properties...
September 2016: Microbiology and Immunology
Daniela A Moraes, Tatiana T Sibov, Lorena F Pavon, Paula Q Alvim, Raphael S Bonadio, Jaqueline R Da Silva, Aline Pic-Taylor, Orlando A Toledo, Luciana C Marti, Ricardo B Azevedo, Daniela M Oliveira
BACKGROUND: Mesenchymal stromal cells (MSCs) are multipotent progenitor cells used in several cell therapies. MSCs are characterized by the expression of CD73, CD90, and CD105 cell markers, and the absence of CD34, CD45, CD11a, CD19, and HLA-DR cell markers. CD90 is a glycoprotein present in the MSC membranes and also in adult cells and cancer stem cells. The role of CD90 in MSCs remains unknown. Here, we sought to analyse the role that CD90 plays in the characteristic properties of in vitro expanded human MSCs...
2016: Stem Cell Research & Therapy
Xiao Na Ge, Sung Gil Ha, Yana G Greenberg, Amrita Rao, Idil Bastan, Ada G Blidner, Savita P Rao, Gabriel A Rabinovich, P Sriramarao
Galectin-1 (Gal-1), a glycan-binding protein with broad antiinflammatory activities, functions as a proresolving mediator in autoimmune and chronic inflammatory disorders. However, its role in allergic airway inflammation has not yet been elucidated. We evaluated the effects of Gal-1 on eosinophil function and its role in a mouse model of allergic asthma. Allergen exposure resulted in airway recruitment of Gal-1-expressing inflammatory cells, including eosinophils, as well as increased Gal-1 in extracellular spaces in the lungs...
August 16, 2016: Proceedings of the National Academy of Sciences of the United States of America
Christina T Jensen, Stefan Lang, Rajesh Somasundaram, Shamit Soneji, Mikael Sigvardsson
Whereas the characterization of B lymphoid progenitors has been facilitated by the identification of lineage- and stage-specific surface markers, the continued identification of differentially expressed proteins increases our capacity to explore normal and malignant B cell development. To identify novel surface markers with stage-specific expression patterns, we explored the reactivity of CD19(+) B cell progenitor cells to Abs targeted to 176 surface proteins. Markers with stage-specific expression were identified using a transgenic reporter gene system subdividing the B cell progenitors into four surface IgM(-) stages...
September 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Xin Liu, Junling Wang, Huiyun Zhang, Mengmeng Zhan, Hanqiu Chen, Zeman Fang, Chiyan Xu, Huifang Chen, Shaoheng He
Mast cells are primary effector cells of allergy, and recruitment of mast cells in involved tissue is one of the key events in allergic inflammation. Tryptase is the most abundant secretory product of mast cells, but little is known of its influence on mast cell accumulation. Using mouse peritoneal model, cell migration assay, and flow cytometry analysis, we investigated role of tryptase in recruiting mast cells. The results showed that tryptase induced up to 6.7-fold increase in mast cell numbers in mouse peritoneum following injection...
2016: Mediators of Inflammation
Charles P Semba, Thomas R Gadek
Dry eye disease (DED) is a multifactorial disorder of the ocular surface characterized by symptoms of discomfort, decreased tear quality, and chronic inflammation that affects an estimated 20 million patients in the US alone. DED is associated with localized inflammation of the ocular surface and periocular tissues leading to homing and activation of T cells, cytokine release, and development of hyperosmolar tears. This inflammatory milieu results in symptoms of eye dryness and discomfort. Homing of T cells to the ocular surface is influenced by the binding of lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18; αLβ2), a cell surface adhesion protein, to its cognate ligand, intercellular adhesion molecule-1 (ICAM-1; CD54), which is expressed on inflamed ocular/periocular epithelium and vascular endothelium...
2016: Clinical Ophthalmology
Daiki Murata, Atsushi Yamasaki, Shouta Matsuzaki, Takafumi Sunaga, Makoto Fujiki, Satoshi Tokunaga, Kazuhiro Misumi
Dedifferentiated fat (DFAT) cells have been shown to be multipotent, similar to mesenchymal stem cells (MSCs). In this study, we aimed to establish and characterize equine DFAT cells. Equine adipocytes were ceiling cultured, and then dedifferentiated into DFAT cells by the seventh day of culture. The number of DFAT cells was increased to over 10 million by the fourth passage. Flow cytometry of DFAT cells showed that the cells were strongly positive for CD44, CD90, and major histocompatibility complex (MHC) class I; moderately positive for CD11a/18, CD105, and MHC class II; and negative for CD34 and CD45...
2016: Journal of Equine Science
Xavier Delabranche, Jean-Pierre Quenot, Thierry Lavigne, Emmanuelle Mercier, Bruno François, François Severac, Lélia Grunebaum, Madah Mehdi, Fatiha Zobairi, Florence Toti, Ferhat Meziani, Julie Boisramé-Helms
OBJECTIVES: Inadequate stratification of septic shock patients may result in inappropriate treatment allocation in randomized clinical trials, especially regarding anticoagulant. We previously reported that endothelial-derived microparticles are relevant biomarkers of sepsis-induced disseminated intravascular coagulation. In this validation cohort, we assess microparticles as surrogates of cell activation to improve early disseminated intravascular coagulation diagnosis and patient stratification...
October 2016: Critical Care Medicine
Young Joon Park, Mi Jin Park, Sun Park, Eun-So Lee
OBJECTIVES: Single nucleotide polymorphisms of CD11a and CD11c have been suggested as susceptibility loci in Korean patients with Behçet's disease (BD). As immunoregulatory roles of CD11c+CD8+T cells were previously observed in multiple autoimmune and autoinflammatory diseases, we aimed to investigate CD11a and CD11c in CD4+ and CD8+ subpopulation of BD patients. METHODS: Peripheral-blood mononuclear cells were isolated from 21 patients with active BD, 26 patients with inactive BD, 20 patients with recurrent aphthous ulcers (RAU), and 23 healthy controls (HCs)...
June 16, 2016: Clinical and Experimental Rheumatology
Yu Guo, Ming Zhao, Qianjin Lu
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease caused by complex interactions between genes and the environment. The expression level of transcription factor regulatory factor X 1 (RFX1) is reduced in T cells from SLE patients. RFX1 can regulate epigenetic modifications of CD70 and CD11a and plays an important role in the development of SLE. However, the mechanisms that mediate reduction of RFX1 in SLE are unclear. Here, we demonstrate that RFX1 protein expression can be tightly regulated by polyubiquitination-mediated proteosomal degradation via STIP1 homology and U-box containing protein 1 (STUB1)...
August 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Jennifer M Loftis, Jonathan Taylor, Hans-Peter Raué, Mark K Slifka, Elaine Huang
Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans...
October 1, 2016: Behavioural Brain Research
Margaret A Highland, David A Schneider, Stephen N White, Sally A Madsen-Bouterse, Donald P Knowles, William C Davis
Although both domestic sheep (DS) and bighorn sheep (BHS) are affected by similar respiratory bacterial pathogens, experimental and field data indicate BHS are more susceptible to pneumonia. Cross-reactive monoclonal antibodies (mAbs) for use in flow cytometry (FC) are valuable reagents for interspecies comparative immune system analyses. This study describes cross-reactive mAbs that recognize leukocyte differentiation molecules (LDMs) and major histocompatibility complex antigens on DS and BHS leukocytes. Characterization of multichannel eosinophil autofluorescence in this study permitted cell-type specific gating of granulocytes for evaluating LDMs, specifically on neutrophils, by single-label FC...
June 2016: Comparative Immunology, Microbiology and Infectious Diseases
Nonzwakazi Bangani, Justine Nakiwala, Adrian R Martineau, Robert J Wilkinson, Katalin A Wilkinson, David M Lowe
: Using a flow cytometric assay we investigated neutrophil-M.tuberculosis opsonophagocytosis and the impact of HIV-1-infected serum on this process. The mean (±SD) percentage of neutrophils internalising bacilli after 30 minutes incubation was significantly reduced by pre-treatment with anti-CD16 (18.2±8.1%, p<0.001) or anti-CD35 antibody (23.2±10.6%, p<0.05) versus anti-CD4 controls (29.9±8.1%). Blocking CD88 or CD11a did not affect internalisation. Using heat-inactivated serum, maximal internalisation was lower using HIV-1-infected serum versus HIV-1-uninfected...
May 31, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Ko-Jen Li, Cheng-Han Wu, Chieh-Yu Shen, Yu-Min Kuo, Chia-Li Yu, Song-Chou Hsieh
The biological significance of membrane transfer (trogocytosis) between polymorphonuclear neutrophils (PMNs) and mononuclear cells (MNCs) remains unclear. We investigated the biological/immunological effects and molecular basis of trogocytosis among various immune cells in healthy individuals and patients with active systemic lupus erythematosus (SLE). By flow cytometry, we determined that molecules in the immunological synapse, including HLA class-I and-II, CD11b and LFA-1, along with CXCR1, are exchanged among autologous PMNs, CD4+ T cells, and U937 cells (monocytes) after cell-cell contact...
2016: PloS One
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