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https://www.readbyqxmd.com/read/28710286/how-tetraspanins-shape-endothelial-and-leukocyte-nano-architecture-during-inflammation
#1
REVIEW
Jonas Franz, Marco Tarantola, Christoph Riethmüller
Tetraspanins are ubiquitous membrane proteins that induce local membrane curvature and hence co-ordinate cell-to-cell contacts. This review highlights their role in inflammation, which requires control of the nano-architecture of attachment sites between endothelial cells and leukocytes. The active role of endothelial cells in preparing for transmigration of leukocytes and determining the severity of an inflammation is often underscored. A clear hint to endothelial pre-activation is their ability to protrude clustered adhesion proteins upward prior to leukocyte contact...
July 14, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28708595/angptl4-promotes-the-progression-of-cutaneous-melanoma-to-brain-metastasis
#2
Sivan Izraely, Shlomit Ben-Menachem, Orit Sagi-Assif, Tsipi Meshel, Diego M Marzese, Shuichi Ohe, Inna Zubrilov, Metsada Pasmanik-Chor, Dave S B Hoon, Isaac P Witz
In an ongoing effort to identify molecular determinants regulating melanoma brain metastasis, we previously identified Angiopoietin-like 4 (ANGPTL4) as a component of the molecular signature of such metastases.The aim of this study was to determine the functional significance of ANGPTL4 in the shaping of melanoma malignancy phenotype, especially in the establishment of brain metastasis.We confirmed that ANGPTL4 expression is significantly higher in cells metastasizing to the brain than in cells from the cutaneous (local) tumor from the same melanoma in a nude mouse xenograft model, and also in paired clinical specimens of melanoma metastases than in primary melanomas from the same patients...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28701303/endothelial-cell-shp-2-negatively-regulates-neutrophil-adhesion-and-promotes-transmigration-by-enhancing-icam-1-ve-cadherin-interaction
#3
Meiping Yan, Xinhua Zhang, Ao Chen, Wei Gu, Jie Liu, Xiaojiao Ren, Jianping Zhang, Xiaoxiong Wu, Aaron T Place, Richard D Minshall, Guoquan Liu
Intercellular adhesion molecule-1 (ICAM-1) mediates the firm adhesion of leukocytes to endothelial cells and initiates subsequent signaling that promotes their transendothelial migration (TEM). Vascular endothelial (VE)-cadherin plays a critical role in endothelial cell-cell adhesion, thereby controlling endothelial permeability and leukocyte transmigration. This study aimed to determine the molecular signaling events that originate from the ICAM-1-mediated firm adhesion of neutrophils that regulate VE-cadherin's role as a negative regulator of leukocyte transmigration...
July 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28691930/ly6clo-monocytes-drive-immunosuppression-and-confer-resistance-to-anti-vegfr2-cancer-therapy
#4
Keehoon Jung, Takahiro Heishi, Omar F Khan, Piotr S Kowalski, Joao Incio, Nuh N Rahbari, Euiheon Chung, Jeffrey W Clark, Christopher G Willett, Andrew D Luster, Seok Hyun Yun, Robert Langer, Daniel G Anderson, Timothy P Padera, Rakesh K Jain, Dai Fukumura
Current anti-VEGF therapies for colorectal cancer (CRC) provide limited survival benefit, as tumors rapidly develop resistance to these agents. Here, we have uncovered an immunosuppressive role for nonclassical Ly6Clo monocytes that mediates resistance to anti-VEGFR2 treatment. We found that the chemokine CX3CL1 was upregulated in both human and murine tumors following VEGF signaling blockade, resulting in recruitment of CX3CR1+Ly6Clo monocytes into the tumor. We also found that treatment with VEGFA reduced expression of CX3CL1 in endothelial cells in vitro...
July 10, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28688659/indole-3-carbinol-is-a-potent-inhibitor-of-ischemia-reperfusion-induced-inflammation
#5
Emmanuel Ampofo, Nico Lachnitt, Jeannette Rudzitis-Auth, Beate M Schmitt, Michael D Menger, Matthias W Laschke
BACKGROUND: Ischemia-reperfusion (I/R) induces tissue inflammation, which is characterized by an increased leukocyte-endothelial cell interaction and leukocyte transmigration. These processes are mediated by the activation of the nuclear factor (NF)κB signaling pathway, resulting in an elevated expression of specific adhesion molecules. The phytochemical indole-3-carbinol (I3C) has been shown to exert anti-inflammatory effects by interfering with NFκB signal transduction. The aim of the present study was to investigate whether I3C is capable of counteracting the pathogenesis of I/R injury...
July 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28676800/atribacteria-from-the-subseafloor-sedimentary-biosphere-disperse-to-the-hydrosphere-through-submarine-mud-volcanoes
#6
Tatsuhiko Hoshino, Tomohiro Toki, Akira Ijiri, Yuki Morono, Hideaki Machiyama, Juichiro Ashi, Kei Okamura, Fumio Inagaki
Submarine mud volcanoes (SMVs) are formed by muddy sediments and breccias extruded to the seafloor from a source in the deep subseafloor and are characterized by the discharge of methane and other hydrocarbon gasses and deep-sourced fluids into the overlying seawater. Although SMVs act as a natural pipeline connecting the Earth's surface and subsurface biospheres, the dispersal of deep-biosphere microorganisms and their ecological roles remain largely unknown. In this study, we investigated the microbial communities in sediment and overlying seawater at two SMVs located on the Ryukyu Trench off Tanegashima Island, southern Japan...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28663244/frontline-science-c-myc-regulates-p-selectin-glycoprotein-ligand-1-expression-in-monocytes-during-hiv-1-infection
#7
Ryan Connor, Letitia D Jones, Xing Qiu, Juilee Thakar, Sanjay B Maggirwar
Leukocyte extravasation is a crucial feature of the normal immune response to disease and infection and is implicated in various pathologies during chronic inflammatory disease. P-Selectin glycoprotein ligand-1 (PSGL-1) is critical for leukocyte extravasation; however, despite extensive study, it remains unclear how its expression is regulated, which in turn, impedes a more precise understanding of how its expression level affects transmigration. To investigate the regulation of PSGL-1, 60 subjects, with or without HIV infection, were recruited and PSGL-1 expression in monocytes was measured...
June 29, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28656176/a-three-dimensional-cell-culture-system-to-model-rna-virus-infections-at-the-blood-brain-barrier
#8
John C Bramley, Coyne G Drummond, Nicholas J Lennemann, Charles A Good, Kwang Sik Kim, Carolyn B Coyne
The blood-brain barrier (BBB) comprises the foremost protective barrier in the brain and is composed in part of a layer of microvascular endothelial cells that line the capillaries surrounding the brain. Here, we describe a human three-dimensional (3-D) cell-based model of the BBB microvascular endothelium that recapitulates properties of these cells in vivo, including physiologically relevant transcriptional profiles, the capacity to induce potent antimicrobial innate immune signaling, and the ability to resist infection by diverse RNA viruses, including members of the enterovirus (coxsackievirus B, echovirus 11, enterovirus 71, poliovirus) and flavivirus (dengue virus, Zika virus [ZIKV]) families...
May 2017: MSphere
https://www.readbyqxmd.com/read/28655384/altered-basophil-function-in-patients-with-chronic-kidney-disease-on-hemodialysis%C3%A2
#9
Zenib Aljadi, Anna Nopp, Ola Winqvist, Aman Russom, Britta Hylander, Stefan Jacobson, Joachim Lundahl
AIMS: Chronic kidney disease (CKD) leads to impairment of immune cell function. Given the potential role of basophils in the pathogenesis of CKD, we aimed to study the basophil responsiveness towards microbial antigen exposure, judged as adhesion molecule expression and degranulation, in CKD patients on hemodialysis. MATERIALS AND METHODS: We selected markers linked to two crucial biological phases: the transmigration and degranulation processes, respectively. For the transmigration process, we selected the adhesion molecules CD11b, active CD11b epitope, and CD62L and for the degranulation process CD203c (piecemeal degranulation marker), CD63 (degranulation marker), and CD300a (inhibitory marker of degranulation)...
June 28, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28650050/bilayered-nanofibrous-3d-hierarchy-as-skin-rudiment-by-emulsion-electrospinning-for-burn-wound-management
#10
Pallabi Pal, Prabhash Dadhich, Pavan Kumar Srivas, Bodhisatwa Das, Dhrubajyoti Maulik, Santanu Dhara
Mimicking skin extracellular matrix hierarchy, the present work aims to develop a bilayer skin graft comprising a porous cotton-wool-like 3D layer with membranous structure of PCL-chitosan nanofibers. Emulsion electrospinning with differential stirring periods of PCL-chitosan emulsion results in development of a bilayer 3D structure with varied morphology. The electrospun membrane has fiber diameter ∼274 nm and pore size ∼1.16 μm while fluffy 3D layer has fiber diameter ∼1.62 μm and pore size ∼62 μm...
June 26, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28645652/androgen-inhibits-key-atherosclerotic-processes-by-directly-activating-adtrp-transcription
#11
Chunyan Luo, Elisabeth Pook, Bo Tang, Weiyi Zhang, Sisi Li, Kirsten Leineweber, Shing-Hu Cheung, Qiuyun Chen, Martin Bechem, Jing-Shan Hu, Volker Laux, Qing Kenneth Wang
Low androgen levels are associated with an increased risk of coronary artery disease (CAD), thrombosis and myocardial infarction (MI), suggesting that androgen has a protective role. However, little is known about the underlying molecular mechanism. Our genome-wide association study identified the ADTRP gene encoding the androgen-dependent TFPI regulating protein as a susceptibility gene for CAD and MI. The expression level of ADTRP was regulated by androgen, but the molecular mechanism is unknown. In this study, we identified the molecular mechanism by which androgen regulates ADTRP expression and tested the hypothesis that androgen plays a protective role in cardiovascular disease by activating ADTRP expression...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28643773/a-cdc42-rhoa-regulatory-circuit-downstream-of-glycoprotein-ib-guides-transendothelial-platelet-biogenesis
#12
Sebastian Dütting, Frederique Gaits-Iacovoni, David Stegner, Michael Popp, Adrien Antkowiak, Judith M M van Eeuwijk, Paquita Nurden, Simon Stritt, Tobias Heib, Katja Aurbach, Oguzhan Angay, Deya Cherpokova, Niels Heinz, Ayesha A Baig, Maximilian G Gorelashvili, Frank Gerner, Katrin G Heinze, Jerry Ware, Georg Krohne, Zaverio M Ruggeri, Alan T Nurden, Harald Schulze, Ute Modlich, Irina Pleines, Cord Brakebusch, Bernhard Nieswandt
Blood platelets are produced by large bone marrow (BM) precursor cells, megakaryocytes (MKs), which extend cytoplasmic protrusions (proplatelets) into BM sinusoids. The molecular cues that control MK polarization towards sinusoids and limit transendothelial crossing to proplatelets remain unknown. Here, we show that the small GTPases Cdc42 and RhoA act as a regulatory circuit downstream of the MK-specific mechanoreceptor GPIb to coordinate polarized transendothelial platelet biogenesis. Functional deficiency of either GPIb or Cdc42 impairs transendothelial proplatelet formation...
June 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28642092/chemokine-ccl17-is-expressed-by-dendritic-cells-in-the-cns-during-experimental-autoimmune-encephalomyelitis-and-promotes-pathogenesis-of-disease
#13
Christina Ruland, Hannes Renken, Ivan Kuzmanov, Arezoo Fattahi Mehr, Kathrin Schwarte, Manuela Cerina, Alexander Herrmann, David-Marian Otte, Andreas Zimmer, Nicholas Schwab, Sven G Meuth, Volker Arolt, Luisa Klotz, Irmgard Förster, Stefanie Scheu, Judith Alferink
The CC chemokine ligand 17 (CCL17) and its cognate CC chemokine receptor 4 (CCR4) are known to control leukocyte migration, maintenance of TH17 cells, and regulatory T cell (Treg) expansion in vivo. In this study we characterized the expression and functional role of CCL17 in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Using a CCL17/EGFP reporter mouse model, we could show that CCL17 expression in the CNS can be found in a subset of classical dendritic cells (DCs) that immigrate into the CNS during the effector phase of MOG-induced EAE...
June 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28637894/deep-insight-into-neutrophil-trafficking-in-various-organs
#14
REVIEW
Young-Min Hyun, Chang-Won Hong
Neutrophils are professional phagocytes that constitute the first line of defense in humans. The primary function of neutrophils is to eliminate invading pathogens through oxidative and nonoxidative mechanisms. Because neutrophils rapidly migrate into inflammatory foci via diapedesis and chemotaxis, neutrophil recruitment has long been considered a hallmark of inflammation. Recent advances in intravital microscopic technologies using animal model systems have enabled researchers to directly visualize neutrophil trafficking...
June 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28636879/delineating-neuroinflammation-parasite-cns-invasion-and-blood-brain-barrier-dysfunction-in-an-experimental-murine-model-of-human-african-trypanosomiasis
#15
Jean Rodgers, Barbara Bradley, Peter G E Kennedy
Although Trypanosoma brucei spp. was first detected by Aldo Castellani in CSF samples taken from sleeping sickness patients over a century ago there is still a great deal of debate surrounding the timing, route and effects of transmigration of the parasite from the blood to the CNS. In this investigation, we have applied contrast-enhance magnetic resonance imaging (MRI) to study the effects of trypanosome infection on the blood-brain barrier (BBB) in the well-established GVR35 mouse model of sleeping sickness...
June 18, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28626344/increased-transendothelial-transport-of-ccl3-is-insufficient-to-drive-immune-cell-transmigration-through-the-blood-brain-barrier-under-inflammatory-conditions-in-vitro
#16
Maxime De Laere, Carmelita Sousa, Megha Meena, Roeland Buckinx, Jean-Pierre Timmermans, Zwi Berneman, Nathalie Cools
Many neuroinflammatory diseases are characterized by massive immune cell infiltration into the central nervous system. Identifying the underlying mechanisms could aid in the development of therapeutic strategies specifically interfering with inflammatory cell trafficking. To achieve this, we implemented and validated a blood-brain barrier (BBB) model to study chemokine secretion, chemokine transport, and leukocyte trafficking in vitro. In a coculture model consisting of a human cerebral microvascular endothelial cell line and human astrocytes, proinflammatory stimulation downregulated the expression of tight junction proteins, while the expression of adhesion molecules and chemokines was upregulated...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28600306/expression-of-lewis-a-glycans-on-polymorphonuclear-leukocytes-augments-function-by-increasing-transmigration
#17
Jennifer C Brazil, Ronen Sumagin, Sean R Stowell, Goo Lee, Nancy A Louis, Richard D Cummings, Charles A Parkos
PMN-expressed fucosylated glycans from the Lewis glycan family, including Lewis-x (Le(x)) and sialyl Lewis-x (sLe(x)), have previously been implicated in the regulation of important PMN functions, including selectin-mediated trafficking across vascular endothelium. Although glycans, such as Le(x) and sLe(x), which are based on the type 2 sequence (Galβ1-4GlcNAc-R), are abundant on PMNs, the presence of type 1 Galβ1-3GlcNAc-R glycans required for PMN expression of the closely related stereoisomer of Le(x), termed Lewis-A (Le(a)), has not, to our knowledge, been reported...
June 9, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28600292/adam10-interacting-tetraspanins-tspan5-and-tspan17-regulate-ve-cadherin-expression-and-promote-t-lymphocyte-transmigration
#18
Jasmeet S Reyat, Myriam Chimen, Peter J Noy, Justyna Szyroka, G Ed Rainger, Michael G Tomlinson
The recruitment of blood leukocytes across the endothelium to sites of tissue infection is central to inflammation, but also promotes chronic inflammatory diseases. A disintegrin and metalloproteinase 10 (ADAM10) is a ubiquitous transmembrane molecular scissor that is implicated in leukocyte transmigration by proteolytically cleaving its endothelial substrates. These include VE-cadherin, a homotypic adhesion molecule that regulates endothelial barrier function, and transmembrane chemokines CX3CL1 and CXCL16, which have receptors on leukocytes...
July 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28596573/fibroblast-growth-factor-23-weakens-chemotaxis-of-human-blood-neutrophils-in-microfluidic-devices
#19
Ke Yang, Hagit Peretz-Soroka, Jiandong Wu, Ling Zhu, Xueling Cui, Michael Zhang, Claudio Rigatto, Yong Liu, Francis Lin
Neutrophil trafficking in tissues critically regulates the body's immune response. Neutrophil migration can either play a protective role in host defense or cause health problems. Fibroblast growth factor 23 (FGF23) is a known biomarker for chronic kidney disease (CKD) and was recently shown to impair neutrophil arrest on endothelium and transendothelial migration. In the present study, we further examined the effect of FGF23 on human blood neutrophil chemotaxis using two new microfluidic devices. Our results showed that chemotaxis of FGF23 pre-treated neutrophils to a fMLP gradient, in the presence or absence of a uniform FGF23 background, is quantitatively lower compared to the control cells...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28596294/the-metalloproteinase-adam8-promotes-leukocyte-recruitment-in-vitro-and-in-acute-lung-inflammation
#20
Daniela Dreymueller, Jessica Pruessmeyer, Julian Schumacher, Sandra Fellendorf, Franz Martin Hess, Anke Seifert, Aaron Babendreyer, Joerg Walter Bartsch, Andreas Ludwig
Alveolar leukocyte recruitment is a hallmark of acute lung inflammation and involves transmigration of leukocytes through endothelial and epithelial layers. The disintegrin and metalloproteinase (ADAM) 8 is expressed on human isolated leukocytic cells and can be further upregulated on cultured endothelial and epithelial cells by proinflammatory cytokines. By shRNA mediated knockdown we show that leukocytic ADAM8 is required on monocytic THP-1 cells for chemokine-induced chemotaxis as well as transendothelial and transepithelial migration...
June 8, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
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