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leukocyte adhesion

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https://www.readbyqxmd.com/read/28229893/safety-and-efficacy-of-natalizumab-in-patients-with-acute-ischaemic-stroke-action-a-randomised-placebo-controlled-double-blind-phase-2-trial
#1
Jacob Elkins, Roland Veltkamp, Joan Montaner, S Claiborne Johnston, Aneesh B Singhal, Kyra Becker, Maarten G Lansberg, Weihua Tang, Ih Chang, Kumar Muralidharan, Sarah Gheuens, Lahar Mehta, Mitchell S V Elkind
BACKGROUND: In animal models of acute ischaemic stroke, blocking of the leukocyte-endothelium adhesion by antagonism of α4 integrin reduces infarct volumes and improves outcomes. We assessed the effect of one dose of natalizumab, an antibody against the leukocyte adhesion molecule α4 integrin, in patients with acute ischaemic stroke. METHODS: In this double-blind, phase 2 study, patients with acute ischaemic stroke (aged 18-85 years) from 30 US and European clinical sites were randomly assigned (1:1) to 300 mg intravenous natalizumab or placebo with stratification by treatment window and baseline infarct size...
March 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28228072/curcumin-and-endothelial-function-evidence-and-mechanisms-of-protective-effects
#2
Maryam Saberi Karimian, Matteo Pirro, Thomas P Johnston, Muhammed Majeed, Amirhossein Sahebkar
BACKGROUND: The endothelium is a large paracrine organ regulating cell growth, vascular tone and thrombogenicity as well as platelet and leukocyte interactions. Endothelial function can be assessed by non-invasive techniques [e.g. flow-mediated vasodilation, nitroglycerin-mediated dilation and pulse wave velocity] and measuring specific circulating biomarkers [cell adhesion molecules, endothelial microparticles and endothelial progenitor cells]. Impaired endothelial function plays a key role in the development of atherosclerosis, arterial hypertension, heart failure, ischemia-reperfusion injury, Alzheimer's disease and other conditions...
February 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28209527/exploring-deformable-particles-in-vascular-targeted-drug-delivery-softer-is-only-sometimes-better
#3
Margaret B Fish, Catherine A Fromen, Genesis Lopez-Cazares, Alexander W Golinski, Timothy F Scott, Reheman Adili, Michael Holinstat, Omolola Eniola-Adefeso
The ability of vascular-targeted drug carriers (VTCs) to localize and bind to a targeted, diseased endothelium determines their overall clinical utility. Here, we investigate how particle modulus and size determine adhesion of VTCs to the vascular wall under physiological blood flow conditions. In general, deformable microparticles (MPs) outperformed nanoparticles (NPs) in all experimental conditions tested. Our results indicate that MP modulus enhances particle adhesion in a shear-dependent manner. In low shear human blood flow profiles in vitro, low modulus particles showed favorable adhesion, while at high shear, rigid particles showed superior adhesion...
February 4, 2017: Biomaterials
https://www.readbyqxmd.com/read/28209483/a-new-size-based-platform-for-circulating-tumor-cell-detection-in-colorectal-cancer-patients
#4
Bo Young Oh, Jhingook Kim, Woo Yong Lee, Hee Cheol Kim
BACKGROUND: Circulating tumor cells (CTCs) might play a significant role in cancer progression and metastasis. However, the ability to detect CTCs is limited, especially in cells undergoing epithelial-mesenchymal transition. In this study, we evaluated a new size-based CTC detection platform and its clinical efficacy in colorectal cancer. PATIENTS AND METHODS: Blood samples were obtained from 76 patients with colorectal cancer and 20 healthy control subjects for CTC analysis...
January 25, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28205383/association-between-leukocyte-telomere-length-and-angiogenic-cytokines-in-knee-osteoarthritis
#5
Thitiya Poonpet, Natthaphon Saetan, Aree Tanavalee, Vajara Wilairatana, Pongsak Yuktanandana, Sittisak Honsawek
AIM: The aims of this study were to compare leukocyte relative telomere length (RTL) in knee osteoarthritis (OA) patients and healthy controls and to investigate associations between plasma angiogenic cytokine concentrations and leukocyte RTL. METHOD: Eighty knee OA patients and 60 age-matched controls were enrolled. Leukocyte RTL was assessed using real-time quantitative polymerase chain reaction (qPCR). Angiogenic cytokines were measured by a multiplex immunoassay...
February 16, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28198418/circulating-classical-monocytes-are-associated-with-cd11c-macrophages-in-human-visceral-adipose-tissue
#6
Kristiaan Wouters, Katrien Gaens, Mitchell Bijnen, Kenneth Verboven, Johan Jocken, Suzan Wetzels, Erwin Wijnands, Dominique Hansen, Marleen van Greevenbroek, Adriaan Duijvestijn, Erik A L Biessen, Ellen E Blaak, Coen D A Stehouwer, Casper G Schalkwijk
Immune cell accumulation in adipose tissue (AT) is associated with the development of AT inflammation, resulting in metabolic dysfunction. Circulating immune cell patterns may reflect immune cell accumulation in expanding AT. However, data linking human leukocytes in blood and AT is lacking. We investigated whether blood immune cell populations are associated with their counterparts in subcutaneous (scAT) or visceral AT (vAT). Flow cytometry was performed on blood, scAT and vAT from 16 lean and 29 obese men...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196865/s-palmitoylation-of-junctional-adhesion-molecule-c-regulates-its-tight-junction-localization-and-cell-migration
#7
Pornpun Aramsangtienchai, Nicole A Spiegelman, Ji Cao, Hening Lin
Junctional Adhesion Molecule C (JAM-C) is an immunoglobulin superfamily protein expressed in epithelial cells, endothelial cells, and leukocytes. JAM-C has been implicated in leukocyte transendothelial migration, angiogenesis, cell-adhesion, cell polarity, spermatogenesis and metastasis. Here, we show that JAM-C undergoes S-palmitoylation on two juxtamembrane cysteine residues, Cys264 and Cys265. We have identified DHHC7 as a JAM-C palmitoylating enzyme by screening all known palmitoyltransferases (PATs or DHHCs)...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28196858/the-2016-walter-b-cannon-lecture-deconstructing-metabolic-inflammation-using-cellular-systems
#8
Kenny L Chan, Parastoo Boroumand, Marciane Milanski, Nicolas J Pillon, Philip J Bilan, Amira Klip
Over the past years we have embarked in a systematic analysis of the effect of obesity or fatty acids on circulating monocytes, microvascular endothelial cells, macrophages and skeletal muscle cells. Using cell culture strategies, we have deconstructed complex physiological systems, then reconstructed 'partial equations' to better understand cell-to-cell communication. Through these approaches we identified that in high saturated fat environments, cell-autonomous pro-inflammatory pathways are activated in monocytes and endothelial cells, promoting monocyte adhesion and transmigration...
February 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28196850/endothelial-cell-activation-in-central-nervous-system-inflammation
#9
REVIEW
Fengjiao Wu, Lixin Liu, Hong Zhou
Leukocyte migration across the endothelial barrier plays an essential role in CNS inflammation. The migration process requires complex endothelial adhesion molecules concentrated at the junctions of endothelial cells. Recent findings suggest that cerebral endothelial cells play an active role in the pathogenesis of CNS inflammatory diseases. This review describes our current understanding of the effects of various inflammatory mediators of leukocyte migration on cerebral endothelial cells, the mechanisms underlying the leukocyte-endothelial cell interactions, and the crosstalk between endothelial cells and glial cells or platelets...
February 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28192190/%C3%AE-7-integrin-and-madcam-1-play-opposing-roles-during-the-development-of-non-alcoholic-steatohepatitis
#10
Hannah K Drescher, Angela Schippers, Thomas Clahsen, Hacer Sahin, Heidi Noels, Mathias Hornef, Norbert Wagner, Christian Trautwein, Konrad L Streetz, Daniela C Kroy
BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in western countries. It is unclear how infiltrating leukocytes affect NASH-development. Hence our study aims to investigate the role of the homing/receptor-pair mucosal addressin cell adhesion molecule-1 (MAdCAM-1)/β7-Integrin for immune cell recruitment and disease progression in a steatohepatitis model. METHODS: Constitutive β7-Integrin deficient (β7(-/-)) and MAdCAM-1 deficient (MAdCAM-1(-/-)) mice were fed high-fat-diet (HFD) for 26 weeks or methionine-choline-deficient-diet (MCD) for 4 weeks...
February 9, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28186503/a-novel-dlx3-pkc-integrated-signaling-network-drives-keratinocyte-differentiation
#11
Elisabetta Palazzo, Meghan D Kellett, Christophe Cataisson, Paul W Bible, Shreya Bhattacharya, Hong-Wei Sun, Anna C Gormley, Stuart H Yuspa, Maria I Morasso
Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the homeobox transcription factor DLX3 and the tumor suppressor p53 co-regulate cell cycle-related signaling and that this mechanism is functionally involved in cutaneous squamous cell carcinoma development. Here we show that DLX3 expression and its downstream signaling depend on protein kinase C α (PKCα) activity in skin...
February 10, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28183734/skap2-is-required-for-%C3%AE-2-integrin-mediated-neutrophil-recruitment-and-functions
#12
Mark Boras, Stephanie Volmering, Arne Bokemeyer, Jan Rossaint, Helena Block, Bernadette Bardel, Veerle Van Marck, Barbara Heitplatz, Stefanie Kliche, Annegret Reinhold, Clifford Lowell, Alexander Zarbock
Integrin activation is required for neutrophil functions. Impaired integrin activation on neutrophils is the hallmark of leukocyte adhesion deficiency (LAD) syndrome in humans, characterized by impaired leukocyte recruitment and recurrent infections. The Src kinase-associated phosphoprotein 2 (Skap2) is involved in integrin functions in different leukocyte subtypes. However, the role of Skap2 in β2 integrin activation and neutrophil recruitment is unknown. In this study, we demonstrate the crucial role of Skap2 in regulating actin polymerization and binding of talin-1 and kindlin-3 to the β2 integrin cytoplasmic domain, thereby being indispensable for β2 integrin activation and neutrophil recruitment...
February 9, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28178038/p-selectin-glycoprotein-ligand-1-in-t-cells
#13
Michael Abadier, Klaus Ley
PURPOSE OF REVIEW: We review P-selectin glycoprotein ligand-1 (PSGL-1) as a selectin and chemokine-binding adhesion molecule. PSGL-1 is widely studied in neutrophils. Here, we focus on T cells, because PSGL-1 was recently described as a major immunomodulatory molecule during viral infection. PSGL-1 also plays a crucial role in T-cell homeostasis by binding to lymphoid chemokines, and can induce tolerance by enhancing the functions of regulatory T cells. RECENT FINDINGS: PSGL-1 was originally described as a leukocyte ligand for P-selectin, but it is actually a ligand for all selectins (P-, L- and E-selectin), binds chemokines, activates integrins and profoundly affects T-cell biology...
February 7, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28177661/anti-inflammatory-effects-of-dabrafenib-in-vitro-and-in-vivo
#14
In-Chul Lee, Jongdoo Kim, Jong-Sup Bae
The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases (drug repositioning). Drug repositioning refers to the development of existing drugs for new indications. Dabrafenib (DAB) is a B-Raf inhibitor and initially used for the treatment of metastatic melanoma therapy. Here, we tested the possible use of DAB in the treatment of lipopolysaccharide (LPS)-mediated vascular inflammatory responses. The anti-inflammatory activities of DAB were determined by measuring permeability, neutrophils adhesion and migration, and activation of pro-inflammatory proteins in LPS-activated human umbilical vein endothelial cells (HUVECs) and mice...
February 3, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28176248/interleukin-18-induced-cell-adhesion-molecule-expression-is-associated-with-feedback-regulation-by-ppar-%C3%AE-and-nf-%C3%AE%C2%BAb-in-apo-e-mice
#15
Owais Mohammad Bhat, P Uday Kumar, N Harishankar, L Ravichandaran, A Bhatia, Veena Dhawan
Focal recruitment of monocytes and lymphocytes is one of the earliest detectable cellular responses in atherosclerotic lesion formation. Endothelium may regulate leukocyte recruitment by expressing specific adhesion molecules. Interleukin-18 is a proinflammatory cytokine that plays an important role in vascular pathologies. The present study highlights the modulation of adhesion molecules and PPAR-γ by IL-18 and proposes a novel feedback mechanism by which PPAR-γ may regulate IL-18 expression. Three groups of normal chow diet-fed, male Apo E-/- mice, aged 12 weeks (n = 6/group) were employed: Gp I, phosphate-buffered saline (PBS) (2 mo): Gp II, recombinant IL-18 (rIL-18) (1 mo) followed by PBS (1 mo); Gp III, rIL-18 (1 mo) followed by pyrrolidine dithiocarbamate (PDTC) (1 mo)...
February 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28170537/adenosine-deaminase-2-induced-hyperpermeability-in-human-retinal-vascular-endothelial-cells-is-suppressed-by-microrna-146b-3p
#16
Yara A Samra, Heba M Saleh, Khaled A Hussein, Nehal M Elsherbiny, Ahmed S Ibrahim, Khaled Elmasry, Sadanand Fulzele, Mamdouh M El-Shishtawy, Laila A Eissa, Mohamed Al-Shabrawey, Gregory I Liou
Purpose: We recently demonstrated that adenosine deaminase-2 (ADA2) contributes to diabetic retinopathy (DR) via up-regulating the production of inflammatory cytokines in macrophages. Also, microRNA (miR)-146b-3p has the ability to inhibit ADA2. The goal of this study was to investigate the potential role of ADA2 and therapeutic benefit of miR-146b-3p in retinal inflammation and endothelial barrier dysfunction during diabetes. Methods: Adenosine deaminase-2 activity was determined by colorimetric method in diabetic human vitreous...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28167648/natalizumab-for-multiple-sclerosis-a-case-in-point-for-the-impact-of-translational-neuroimmunology
#17
Afsaneh Shirani, Olaf Stüve
Advances in translational neuroimmunology over the last two decades have revolutionized the treatment of relapsing forms of multiple sclerosis. A pathological hallmark of multiple sclerosis is the presence of leukocytes in the areas of disease activity in the CNS. Natalizumab inhibits the trafficking of lymphocytes from the blood into the brain and spinal cord by blocking the adhesion molecule α4-integrin. Representing the enormous success of a molecular targeted approach, natalizumab was the first mAb approved for the treatment of relapsing-remitting multiple sclerosis...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28167274/characterization-of-human-leukocyte-huvec-adhesion-effect-of-cell-preparation-methods
#18
Franca Marino, Laura Schembri, Emanuela Rasini, Monica Pinoli, Angela Scanzano, Alessandra Luini, Terenzio Congiu, Marco Cosentino
OBJECTIVE: Sample manipulation to obtain isolated granulocytes represents a key, and often necessary, step in the in vitro studies. We investigated by the means of flow cytometry and microscopic techniques (both optical microscopy [OM] and scanning electron microscopy [SEM]), the granulocyte-endothelium adhesion and the role of sample manipulation. METHODS: By means of a co-culture method, we have analysed the adhesion of human leukocytes, originated from two different blood samples (fresh venous blood [FB] and buffy coat [BC]), to the human umbilical venous endothelial cell (HUVEC) monolayer...
February 3, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28167044/hypoxia-directs-human-extravillous-trophoblast-differentiation-in-a-hypoxia-inducible-factor-dependent-manner
#19
Anna K Wakeland, Francesca Soncin, Matteo Moretto-Zita, Ching-Wen Chang, Mariko Horii, Don Pizzo, Katharine K Nelson, Louise C Laurent, Mana M Parast
Villous cytotrophoblasts are epithelial stem cells of the early human placenta, able to differentiate either into syncytiotrophoblasts in floating chorionic villi or extravillous trophoblasts (EVTs) at the anchoring villi. The signaling pathways regulating differentiation into these two lineages are incompletely understood. The bulk of placental growth and development in the first trimester occurs under low oxygen tension. One major mechanism by which oxygen regulates cellular function is through the hypoxia-inducible factor (HIF), a transcription factor complex stabilized under low oxygen tension to mediate cellular responses, including cell fate decisions...
February 3, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28166932/hyaluronan-mediates-the-adhesion-of-porcine-peripheral-blood-mononuclear-cells-to-poly-i-c-treated-intestinal-cells-and-modulates-their-cytokine-production
#20
María José Docampo, Jennifer Cabrera, Anna Bassols
Hyaluronan (HA), a major component of the extracellular matrix (ECM), has been increasingly recognized as a regulator of inflammation. Its role is complex since it has pro- and anti-inflammatory actions by modulating the expression of inflammatory genes, the recruitment of inflammatory cells and the production of inflammatory cytokines, but also by attenuating the course of inflammation and providing protection against tissue damage. Certain viruses and other inflammatory stimuli induce organization of HA into cable-like structures, which may be responsible for leukocyte recruitment and, on the other hand, low molecular weight fragments of HA have been shown to activate various inflammatory responses...
February 2017: Veterinary Immunology and Immunopathology
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