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leukocyte adhesion

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https://www.readbyqxmd.com/read/28526034/differential-darc-ackr1-expression-distinguishes-venular-from-non-venular-endothelial-cells-in-murine-tissues
#1
Aude Thiriot, Carolina Perdomo, Guiying Cheng, Igor Novitzky-Basso, Sara McArdle, Jamie K Kishimoto, Olga Barreiro, Irina Mazo, Robinson Triboulet, Klaus Ley, Antal Rot, Ulrich H von Andrian
BACKGROUND: Intravascular leukocyte recruitment in most vertebrate tissues is restricted to postcapillary and collecting venules, whereas capillaries and arterioles usually support little or no leukocyte adhesion. This segmental restriction is thought to be mediated by endothelial, rather than hemodynamic, differences. The underlying mechanisms are largely unknown, in part because effective tools to distinguish, isolate, and analyze venular endothelial cells (V-ECs) and non-venular endothelial cells (NV-ECs) have been unavailable...
May 19, 2017: BMC Biology
https://www.readbyqxmd.com/read/28523588/advances-in-the-development-of-janus-kinase-inhibitors-in-inflammatory-bowel-disease-future-prospects
#2
Mathurin Flamant, Josselin Rigaill, Stephane Paul, Xavier Roblin
Inflammatory bowel disease (IBD) is caused by a dysregulation of the immune system, inducing the production of proinflammatory cytokines and adhesion molecules. A better understanding of the mucosal immune response in IBD has led to the development of new drugs directed at inflammatory cytokines and leukocyte-trafficking molecules. Beyond tumor necrosis factor antagonists and anti-integrin molecules, which act by blocking the interaction between gut-specific lymphocytes and their receptor on vascular endothelium, the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway represents a new target in IBD...
May 18, 2017: Drugs
https://www.readbyqxmd.com/read/28521868/metabolic-syndrome-enhances-endoplasmic-reticulum-oxidative-stress-and-leukocyte-endothelium-interactions-in-pcos
#3
Celia Bañuls, Susana Rovira-Llopis, Aranzazu Martinez de Marañon, Silvia Veses, Ana Jover, Marcelino Gomez, Milagros Rocha, Antonio Hernandez-Mijares, Victor M Victor
OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with insulin resistance, which can lead to metabolic syndrome (MetS). Oxidative stress and leukocyte-endothelium interactions are related to PCOS. Our aim was to evaluate whether the presence of MetS in PCOS patients can influence endoplasmic reticulum (ER) and oxidative stress and leukocyte-endothelium interactions. MATERIAL AND METHODS: This was a prospective controlled study conducted in an academic medical center...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28515901/experimental-identification-and-computational-characterization-of-a-novel-extracellular-metalloproteinase-produced-by-clostridium-sordellii
#4
Michael J Aldape, Aoxiang Tao, Dustin D Heeney, Eric R McIndoo, John M French, Dong Xu
Clostridium sordellii is a lethal pathogen for both animals and humans. Severe capillary leakage, toxic shock syndrome, and an extreme leukemoid reaction (LR), are hallmark features of C. sordellii infections and contribute to its high mortality rate. Here we report the discovery of a previously unknown and uncharacterized metalloproteinase of C. sordellii (referred as Mcs1) that cleaves human vascular cell adhesion molecule (VCAM)-1 in vitro, an adhesion molecule critical to hematopoietic precursor retention and leukocyte diapedesis...
March 2, 2017: RSC Advances
https://www.readbyqxmd.com/read/28515093/circulating-soluble-p-selectin-must-dimerize-to-promote-inflammation-and-coagulation-in-mice
#5
Sumith R Panicker, Padmaja Mehta-D'souza, Nan Zhang, Arkadiusz G Klopocki, Bojing Shao, Rodger P McEver
Leukocyte adhesion to P-selectin on activated platelets and endothelial cells induces shedding of the P-selectin ectodomain into the circulation. Plasma soluble P-selectin (sP-selectin) is elevated 3-4-fold in patients with cardiovascular disease. Circulating sP-selectin is thought to trigger signaling in leukocytes that directly contributes to inflammation and thrombosis. However, sP-selectin likely circulates as a monomer, and in vitro studies suggest that sP-selectin must dimerize to induce signaling in leukocytes...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28511346/potential-therapeutic-action-of-nitrite-in-sickle-cell-disease
#6
Nadeem Wajih, Swati Basu, Anuj Jailwala, Hee Won Kim, David Ostrowski, Andreas Perlegas, Crystal A Bolden, Nancy L Buechler, Mark T Gladwin, David L Caudell, Elaheh Rahbar, Martha A Alexander-Miller, Vidula Vachharajani, Daniel B Kim-Shapiro
Sickle cell disease is caused by a mutant form of hemoglobin that polymerizes under hypoxic conditions, increasing rigidity, fragility, calcium influx-mediated dehydration, and adhesivity of red blood cells. Increased red cell fragility results in hemolysis, which reduces nitric oxide (NO) bioavailability, and induces platelet activation and inflammation leading to adhesion of circulating blood cells. Nitric Oxide inhibits adhesion and platelet activation. Nitrite has emerged as an attractive therapeutic agent that targets delivery of NO activity to areas of hypoxia through bioactivation by deoxygenated red blood cell hemoglobin...
May 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/28509340/prf-based-matrices-to-improve-angiogenesis-in-an-in-vitro-co-culture-model-for-bone-tissue-engineering
#7
Eva Dohle, Karima El Bagdadi, Robert Sader, Joseph Choukroun, C James Kirkpatrick, Shahram Ghanaati
In the context of prevascularization strategies for tissue engineering purposes, co-culture systems consisting of outgrowth endothelial cells (OECs) and primary osteoblasts (pOBs) have been established as a promising in vitro tool to study regeneration mechanisms and to identify factors that might positively influence repair processes like wound healing or angiogenesis. The development of autologous injectable platelet rich fibrin (PRF), which can be generated from peripheral blood in a minimal invasive procedure, fulfils several requirements for clinically applicable cell-based tissue engineering strategies...
May 16, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28509283/in-vivo-molecular-mri-of-icam-1-expression-on-endothelium-and-leukocytes-from-subacute-to-chronic-stages-after-experimental-stroke
#8
Lisette H Deddens, Geralda A F van Tilborg, Kajo van der Marel, Hedi Hunt, Annette van der Toorn, Max A Viergever, Helga E de Vries, Rick M Dijkhuizen
Molecular MRI allows in vivo detection of vascular cell adhesion molecules expressed on inflamed endothelium, which enables detection of specific targets for anti-neuroinflammatory treatment. We explored to what extent MR contrast agent targeted to intercellular adhesion molecule-1 (ICAM-1) could detect endothelial- and leukocyte-associated ICAM-1 expression at different stages after experimental stroke. Furthermore, we assessed potential interfering effects of ICAM-1-targeted contrast agent on post-stroke lesion growth...
May 16, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28503993/dual-inhibition-of-pi3k-and-mtor-by-vs-5584-suppresses-thrombus-formation
#9
Thomas Später, Isabelle Müller, Hermann Eichler, Michael D Menger, Matthias W Laschke, Emmanuel Ampofo
VS-5584 is a highly selective dual kinase inhibitor which suppresses phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) activity. Because these kinases are crucially involved in primary hemostasis, we herein investigated the effect of this compound on thrombus formation in vitro and in vivo. Pretreatment of washed platelets (WP) or platelet-rich plasma (PRP) with VS-5584 inhibited the agonist-induced activation of surface glycoprotein complex (GP)IIb/IIIa and the upregulation of P-selectin...
May 15, 2017: Platelets
https://www.readbyqxmd.com/read/28503576/sirtuin-2-regulates-microvascular-inflammation-during-sepsis
#10
Nancy Buechler, Xianfeng Wang, Barbara K Yoza, Charles E McCall, Vidula Vachharajani
Objective. Sepsis and septic shock, the leading causes of death in noncoronary intensive care units, kill more than 200,000/year in the US alone. Circulating cell-endothelial cell interactions are the rate determining factor in sepsis inflammation. Sirtuin, a seven-member family of proteins (SIRT1-7), epigenetically controls inflammation. We have studied the roles of SIRTs 1, 3, and 6 in sepsis previously. In this project, we studied the role of SIRT2 on sepsis-related inflammation. Methods. Sepsis was induced in C57Bl/6 (WT), SIRT2 knockout (SIRT2KO), and SIRT2 overexpressing (SIRT2KI) mice by cecal ligation and puncture (CLP)...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28500072/the-upregulation-of-integrin-%C3%AE-d%C3%AE-2-cd11d-cd18-on-inflammatory-macrophages-promotes-macrophage-retention-in-vascular-lesions-and-development-of-atherosclerosis
#11
Moammir H Aziz, Kui Cui, Mitali Das, Kathleen E Brown, Christopher L Ardell, Maria Febbraio, Elzbieta Pluskota, Juying Han, Huaizhu Wu, Christie M Ballantyne, Jonathan D Smith, Martha K Cathcart, Valentin P Yakubenko
Macrophage accumulation is a critical step during development of chronic inflammation, initiating progression of many devastating diseases. Leukocyte-specific integrin αDβ2 (CD11d/CD18) is dramatically upregulated on macrophages at inflammatory sites. Previously we found that CD11d overexpression on cell surfaces inhibits in vitro cell migration due to excessive adhesion. In this study, we have investigated how inflammation-mediated CD11d upregulation contributes to macrophage retention at inflammatory sites during atherogenesis...
May 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28497779/l-selectin-mechanochemistry-restricts-neutrophil-priming-in-vivo
#12
Zhenghui Liu, Tadayuki Yago, Nan Zhang, Sumith R Panicker, Ying Wang, Longbiao Yao, Padmaja Mehta-D'souza, Lijun Xia, Cheng Zhu, Rodger P McEver
Circulating neutrophils must avoid premature activation to prevent tissue injury. The leukocyte adhesion receptor L-selectin forms bonds with P-selectin glycoprotein ligand-1 (PSGL-1) on other leukocytes and with peripheral node addressin (PNAd) on high endothelial venules. Mechanical forces can strengthen (catch) or weaken (slip) bonds between biological molecules. How these mechanochemical processes influence function in vivo is unexplored. Here we show that mice expressing an L-selectin mutant (N138G) have altered catch bonds and prolonged bond lifetimes at low forces...
May 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28497397/xuebijing-injection-and-resolvin-d1-synergize-to-regulate-leukocyte-adhesion-and-improve-survival-rate-in-mice-with-sepsis-induced-lung-injury
#13
Shu-Kun Zhang, Yu-Zhen Zhuo, Cai-Xia Li, Lei Yang, Hong-Wei Gao, Xi-Mo Wang
OBJECTIVES: To investigate the effect of combined application of Xuebijing Injection ( , XBJ) and resolvin D1 (RvD1) on survival rate and the underlying mechanisms in mice with sepsisinduced lung injury. METHODS: The cecal ligation and puncture (CLP) method was used to develop a mouse sepsis model. Specifific pathogen free male C57BL/6 mice were randomly divided into 5 groups (n=20 each): sham, CLP, CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1. After surgery, mice in the CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1 groups were given XBJ (25 μL/g body weight), RvD1 (10 ng/g body weight), and their combination (the same dose of XBJ and RvD1), respectively...
May 11, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28489325/reducing-macro-and-microheterogeneity-of-n-glycans-enabled-solving-the-crystal-structure-of-the-lectin-and-egf-like-domains-of-human-l-selectin-at-1-9-%C3%A3-resolution
#14
Stefanie Wedepohl, Jens Dernedde, Ardeschir Vahedi-Faridi, Rudolf Tauber, Wolfram Saenger, Haydar Bulut
L-selectin is a cell adhesion receptor located on the surface of most leukocytes and contains a total of 7 N-glycosylation sites. To obtain the crystal structure of human L-selectin, we expressed a shortened version comprising the C-type lectin and EGF-like domains of L-selectin (termed LE hereafter) and systematically analysed mutations of the three glycosylation sites at Asn22, Asn66, and Asn139 in order to reduce macroheterogeneity. After we further removed microheterogeneity, we obtained crystals which diffracted X-rays up to 1...
May 10, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28487256/lipopolysaccharide-lps-induced-pulmonary-neutrophil-recruitment-and-platelet-activation-is-mediated-via-the-p2y1-and-p2y14-receptors-in-mice
#15
R T Amison, S Arnold, B G O'Shaughnessy, S J Cleary, J Ofoedu, M Idzko, C P Page, S C Pitchford
Platelet activation occurs during host defence and in various inflammatory disorders. In animal models of infection and inflammation, experimental depletion of platelets leads to significantly reduced leukocyte recruitment and impaired clearance of pathogens from the lung. It is now appreciated that purinergic receptor activation is required for leukocyte activation, motility and adhesion, and platelet interactions with leukocytes can be modulated by purinergic stimulation of platelets. Here, we have investigated the role of platelet P2Y1, P2Y12, P2Y14, and P2X1 receptors on leukocyte recruitment and chemotaxis...
May 6, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28486940/binding-of-plasmodium-falciparum-to-cd36-can-be-shielded-by-the-glycocalyx
#16
Casper Hempel, Christian William Wang, Jørgen Anders Lindholm Kurtzhals, Trine Staalsø
BACKGROUND: Plasmodium falciparum-infected erythrocytes sequester in the microcirculation due to interaction between surface-expressed parasite proteins and endothelial receptors. Endothelial cells are covered in a carbohydrate-rich glycocalyx that shields against undesired leukocyte adhesion. It was investigated if the cellular glycocalyx affects the binding of P. falciparum-infected erythrocytes to CD36 in vitro. METHODS: Glycocalyx growth was followed in vitro by using azido sugars and cationized ferritin detecting O-glycoproteins and negatively charged proteoglycans, respectively...
May 10, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28486793/inflammatory-bowel-disease-updates-on-molecular-targets-for-biologics
#17
REVIEW
Konstantinos H Katsanos, Konstantinos A Papadakis
Therapy for inflammatory bowel disease (IBD) has changed, with several new agents being evaluated. The era of anti-tumor necrosis factor (anti-TNF) antibody therapy saw remarkable progress in IBD therapy. Some patients, however, do not respond to anti-TNF treatment, or their response decreases over time. This phenomenon highlights the need to identify new molecular targets for therapy in IBD. The targets of new therapeutic molecules in IBD must aim to restore immune dysregulation by the inhibition of proinflammatory cytokines (TNF-α, interleukin [IL]-6, IL-13, IL-17, IL-18, and IL-21) and augmentation of the effect of anti-inflammatory cytokines (IL-10, IL-11, and transforming growth factor β) and to pursue new anti-inflammatory targets, such as regulatory T-cell therapy, Smad7 antisense, Janus-activated kinase inhibition, Toll-like receptor stimulation, leukocyte adhesion, and blockade of T-cell homing via integrins and mucosal addressin cellular adhesion molecule-1...
May 11, 2017: Gut and Liver
https://www.readbyqxmd.com/read/28484055/endothelial-cd2ap-binds-the-receptor-icam-1-to-control-mechanosignaling-leukocyte-adhesion-and-the-route-of-leukocyte-diapedesis-in-vitro
#18
Antje Schaefer, Trynette J van Duijn, Jisca Majolee, Keith Burridge, Peter L Hordijk
Inflammation is driven by excessive transmigration (diapedesis) of leukocytes from the blood to the tissue across the endothelial cell monolayer that lines blood vessels. Leukocyte adhesion, crawling, and transmigration are regulated by clustering of the endothelial mechanosensitive receptor intercellular adhesion molecule-1 (ICAM-1). Whereas several proteins are known to promote ICAM-1 function, the molecular mechanisms that limit ICAM-1-mediated adhesion to prevent excessive leukocyte transmigration remain unknown...
May 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28483911/cd99-derived-agonist-ligands-inhibit-fibronectin-induced-activation-of-%C3%AE-1-integrin-through-pka-shp2-erk-ptpn12-fak-signaling-pathway
#19
Kyoung-Jin Lee, Yuri Kim, Yeon Ho Yoo, Min-Seo Kim, Sun-Hee Lee, Chang-Gyum Kim, Kyeonghan Park, Dooil Jeoung, Hansoo Lee, In Young Ko, Jang-Hee Hahn
The human CD99 protein is a 32kDa glycosylated transmembrane protein that regulates various cellular responses including cell adhesion and leukocyte extravasation. We previously reported that CD99 activation suppresses β1 integrin activity through dephosphorylation of FAK at Y397. We explored a molecular mechanism underlying the suppression of β1 integrin activity by CD99 agonists and its relevance to tumor growth in vivo CD99-Fc fusion proteins or a series of CD99-derived peptides suppressed β1 integrin activity by specifically interacting with three conserved motifs of the CD99 extracellular domain...
May 8, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28483571/sinigrin-attenuates-the-progression-of-atherosclerosis-in-apoe-mice-fed-a-high-cholesterol-diet-potentially-by-inhibiting-vcam-1-expression
#20
Yeon Jeong Jang, Bongkyun Park, Hee-Weon Lee, Hye Jin Park, Hyun Jung Koo, Byung Oh Kim, Eun-Hwa Sohn, Sung Hee Um, Suhkneung Pyo
Atherosclerosis is a complex inflammatory disease associated with elevated levels of atherogenic molecules for leukocyte recruitment. Sinigrin (2-propenylglucosinolate) is found mainly in broccoli, brussels sprouts, and black mustard seeds. Recently, sinigrin has received attention for its role in disease prevention and health promotion. In this study, we examined the effect of sinigrin on development of atherosclerosis in ApoE(-/-) mice and the expression of adhesion molecules in vascular smooth muscle cells (VSMCs)...
May 5, 2017: Chemico-biological Interactions
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