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https://www.readbyqxmd.com/read/29282280/ligand-specific-binding-forces-of-lfa-1-and-mac-1-in-neutrophil-adhesion-and-crawling
#1
Ning Li, Hao Yang, Manliu Wang, Shouqin Lü, Yan Zhang, Mian Long
Lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1), and their counter-receptors such as intercellular cell adhesion molecule (ICAM)-1 and ICAM-2, junctional adhesion molecule (JAM)-A, JAM-C and receptor for advanced glycation end products (RAGE) are crucial to promote polymorphonuclear leukocyte (neutrophil, PMN) recruitment. The underlying mechanisms of ligand-specific bindings in this cascade remain incompletely known. We compared the dynamic force spectrum for various LFA-1/Mac-1-ligand bonds using single molecule atomic force microscopy (AFM) and tested their functions to mediate PMN recruitment under in vitro shear flow...
December 27, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29273735/the-opposing-forces-of-shear-flow-and-sphingosine-1-phosphate-control-marginal-zone-b-cell-shuttling
#2
Kerry Tedford, Michael Steiner, Stanislav Koshutin, Karin Richter, Laura Tech, Yannik Eggers, Inga Jansing, Kerstin Schilling, Anja Erika Hauser, Mark Korthals, Klaus-Dieter Fischer
Splenic marginal zone B cells (MZB) shuttle between the blood-filled marginal zone for antigen collection and the follicle for antigen delivery. However, it is unclear how MZBs migrate directionally from the marginal zone to the follicle. Here, we show that murine MZBs migrate up shear flow via the LFA-1 (αLβ2) integrin ligand ICAM-1, but adhere or migrate down the flow via the VLA-4 integrin (α4β1) ligand VCAM-1. MZBs lacking Arhgef6 (Pak-interacting exchange factor (αPIX)) or functional LFA-1 are impaired in shuttling due to mislocalization toward the VCAM-1-rich red pulp...
December 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29244882/%C3%AE-ii-spectrin-in-t-cells-is-involved-in-the-regulation-of-cell-cell-contact-leading-to-immunological-synapse-formation
#3
Justyna M Meissner, Aleksander F Sikorski, Tomasz Nawara, Jakub Grzesiak, Krzysztof Marycz, Dżamila M Bogusławska, Izabela Michalczyk, Marie-Christine Lecomte, Beata Machnicka
T-lymphocyte activation after antigen presentation to the T-Cell Receptor (TCR) is a critical step in the development of proper immune responses to infection and inflammation. This dynamic process involves reorganization of the actin cytoskeleton and signaling molecules at the cell membrane, leading to the formation of the Immunological Synapse (IS). The mechanisms regulating the formation of the IS are not completely understood. Nonerythroid spectrin is a membrane skeletal protein involved in the regulation of many cellular processes, including cell adhesion, signaling and actin cytoskeleton remodeling...
2017: PloS One
https://www.readbyqxmd.com/read/29236548/budesonide-instillation-immediately-after-reperfusion-ameliorates-ischemia-reperfusion-induced-injury-in-the-transplanted-lung-of-rat
#4
Wei Gao, Qiu-Ming Meng, Xiao-Guang Cui
PURPOSE: Lung ischemia-reperfusion injury (LIRI) after lung transplantation can lead to primary graft dysfunction. Budesonide can improve endothelial function to reduce lung injury. This study was aimed to examine the effects of budesonide on LIRI and potential mechanisms. METHODS: Wistar rats were randomized and transplanted with syngeneic left lung or received the sham surgery. The recipients were instilled with saline or budesonide immediately after reperfusion...
December 13, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/29233918/rhob-controls-the-rab11-mediated-recycling-and-surface-reappearance-of-lfa-1-in-migrating-t-lymphocytes
#5
Malin Samuelsson, Katarzyna Potrzebowska, Janne Lehtonen, Jason P Beech, Ekatarina Skorova, Heli Uronen-Hansson, Lena Svensson
The regulation of cell adhesion and motility is complex and requires the intracellular trafficking of integrins to and from sites of cell adhesion, especially in fast-moving cells such as leukocytes. The Rab family of guanosine triphosphatases (GTPases) is essential for vesicle transport, and vesicles mediate intracellular integrin trafficking. We showed that RhoB regulates the vesicular transport of the integrin LFA-1 along the microtubule network in migrating T lymphocytes. Impairment in RhoB function resulted in the accumulation of both LFA-1 and the recycling endosomal marker Rab11 at the rear of migrating T lymphocytes and decreased the association between these molecules...
December 12, 2017: Science Signaling
https://www.readbyqxmd.com/read/29229906/direction-of-actin-flow-dictates-integrin-lfa-1-orientation-during-leukocyte-migration
#6
Pontus Nordenfelt, Travis I Moore, Shalin B Mehta, Joseph Mathew Kalappurakkal, Vinay Swaminathan, Nobuyasu Koga, Talley J Lambert, David Baker, Jennifer C Waters, Rudolf Oldenbourg, Tomomi Tani, Satyajit Mayor, Clare M Waterman, Timothy A Springer
Integrin αβ heterodimer cell surface receptors mediate adhesive interactions that provide traction for cell migration. Here, we test whether the integrin, when engaged to an extracellular ligand and the cytoskeleton, adopts a specific orientation dictated by the direction of actin flow on the surface of migrating cells. We insert GFP into the rigid, ligand-binding head of the integrin, model with Rosetta the orientation of GFP and its transition dipole relative to the integrin head, and measure orientation with fluorescence polarization microscopy...
December 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/29207960/decreased-expression-of-the-%C3%AE-2-integrin-on-tumor-cells-is-associated-with-a-reduction-in-liver-metastasis-of-colorectal-cancer-in-mice
#7
Aitor Benedicto, Joana Marquez, Alba Herrero, Elvira Olaso, Elzbieta Kolaczkowska, Beatriz Arteta
BACKGROUND: Lymphocyte Function-Associated Antigen-1 (LFA-1; CD18/CD11a) is one of the main adhesion molecules used by immune cells to infiltrate the liver under inflammatory conditions. Recently, the expression of this integrin has also been reported on several solid tumors, including colorectal cancer. However, its functional role in the metastatic progression to the liver remains unknown. Using in vitro assays and an experimental orthotopic in vivo model of liver metastasis, we aimed to elucidate the role of tumor LFA-1 in the metastatic progression by means of the partial depletion of the β2 subunit of LFA-1, required for integrin activation, firm adhesion and signaling...
December 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29180515/migration-against-the-direction-of-flow-is-lfa-1-dependent-in-human-hematopoietic-stem-and-progenitor-cells
#8
Alexander Buffone, Nicholas R Anderson, Daniel A Hammer
The recruitment of immune cells during inflammation is regulated by a multi-step cascade of cell rolling, activation, adhesion, and transmigration through the endothelial barrier. Similarly, Hematopoietic Stem and Progenitor Cells (HSPCs) use this pathway to migrate and home to the bone marrow. After selectin-mediated braking, HSPCs migrate along the vascular endothelium on adhesion ligands including ICAM-1, VCAM-1 or MAdCAM-1. Here we report that both the KG1a stem cell line and primary bone marrow CD34+ HSPCs can migrate against the direction of fluid flow on surfaces coated with cell adhesion molecules (CAMs), a behavior thus far only reported in T lymphocytes...
November 27, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29150976/salt-bridge-interactions-within-the-%C3%AE-2-integrin-%C3%AE-7-helix-mediate-force-induced-binding-and-shear-resistance-ability
#9
Xiao Zhang, Linda Li, Ning Li, Xinyu Shu, Lüwen Zhou, Shouqin Lü, Shenbao Chen, Debin Mao, Mian Long
The functional performance of αI domain α7 helix in β2 integrin activation depends on the allostery of the α7 helix, which axially slides down; therefore, it is critical to elucidate what factors regulate the allostery. In this study, we determined that there were two conservative salt bridge interaction pairs that constrain both the upper and bottom ends of the α7 helix. Molecular Dynamics (MD) simulations for three β2 integrin members of LFA-1 (αL β2 ), Mac-1 (αM β2 ) and αx β2 indicated that the magnitude of the salt bridge interaction is related to the stability of the αI domain and the strength of the corresponding force-induced allostery...
November 18, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29127148/ubc9-binds-to-adap-and-is-required-for-rap1-membrane-recruitment-rac1-activation-and-integrin-mediated-t-cell-adhesion
#10
Yiwei Xiong, Chengjin Ye, Naiqi Yang, Madanqi Li, Hebin Liu
Although the immune adaptor adhesion and degranulation-promoting adaptor protein (ADAP) acts as a key mediator of integrin inside-out signaling leading to T cell adhesion, the regulation of this adaptor during integrin activation and clustering remains unclear. We now identify Ubc9, the sole small ubiquitin-related modifier E2 conjugase, as an essential regulator of ADAP where it is required for TCR-induced membrane recruitment of the small GTPase Rap1 and its effector protein RapL and for activation of the small GTPase Rac1 in T cell adhesion...
November 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29123958/expression-of-cd94-by-ex-vivo-differentiated-nk-cells-correlates-with-the-in-vitro-and-in-vivo-acquisition-of-cytotoxic-features
#11
Meriem Hasmim, Nadine Khalife, Yanyan Zhang, Manale Doldur, Geralidne Visentin, Stéphane Terry, Julien Giron-Michel, Ruoping Tang, François Delhommeau, Nicolas Dulphy, Jean-Henri Bourhis, Fawzia Louache, Salem Chouaib
The administration of ex vivo-expanded Natural Killer (NK) cells in leukemia therapy is still challenging, in part due to the difficulty to generate in sufficient quantities fully mature and functional NK cells and Identification of surface markers indicative of NK maturation and functionality is therefore needed. Here, based on the analysis of surface receptors of ex vivo-expanded NK cells, we identified CD94 as a surface marker correlating with high lytic potential against leukemic cell lines and immunological synapse formation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29100055/extracellular-isg15-signals-cytokine-secretion-through-the-lfa-1-integrin-receptor
#12
Caleb D Swaim, Ariella F Scott, Larissa A Canadeo, Jon M Huibregtse
ISG15 is a ubiquitin-like protein that functions in innate immunity both as an intracellular protein modifier and as an extracellular signaling molecule that stimulates IFN-γ secretion. The extracellular function, important for resistance to mycobacterial disease, has remained biochemically uncharacterized. We have established an NK-92 cell-based assay for IFN-γ release, identified residues critical for ISG15 signaling, and identified the cell surface receptor as LFA-1 (CD11a/CD18; αLβ2 integrin). LFA-1 inhibition blocked IFN-γ secretion, splenocytes from CD11a(-/-) mice did not respond to ISG15, and ISG15 bound directly to the αI domain of CD11a in vitro...
November 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29099772/role-of-lfa-1-and-icam-1-in-cancer
#13
REVIEW
Manuel Reina, Enric Espel
The lymphocyte function-associated antigen-1 (LFA-1) (also known as CD11a/CD18 and αLβ₂), is just one of many integrins in the human body, but its significance is derived from its exclusive presence in leukocytes. In this review, we summarize the studies relating LFA-1 and its major ligand ICAM-1 (or CD54) with cancer, through the function of lymphocytes and myeloid cells on tumor cells. We consider how LFA-1 mediates the interaction of leukocytes with tumors and the role of ICAM-1 in tumor dynamics, which can be independent of its interaction with LFA-1...
November 3, 2017: Cancers
https://www.readbyqxmd.com/read/29098911/targeted-treatments-for-hidradenitis-suppurativa-a-review-of-the-current-literature-and-ongoing-clinical-trials
#14
Melody Maarouf, Ashley K Clark, Dylan E Lee, Vivian Y Shi
PURPOSE: Targeted, immune-modulating drugs are at the forefront of therapy for HS, and a comprehensive clinical trial registry is needed to facilitate data pooling and clinical efficacy comparison. MATERIALS AND METHODS: A systematic review of the ClinicalTrials.gov database was searched for planned, in-progress, completed, or terminated trials investigating the effect of targeted biologic therapies for hidradenitis suppurativa (HS). When results of RCTs were not available, case reports or series were included...
November 10, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29081775/lfa-1-mediates-cytotoxicity-and-tissue-migration-of-specific-cd8-t-cells-after-heterologous-prime-boost-vaccination-against-trypanosoma-cruzi-infection
#15
Camila Pontes Ferreira, Leonardo Moro Cariste, Fernando Dos Santos Virgílio, Barbara Ferri Moraschi, Caroline Brandão Monteiro, Alexandre M Vieira Machado, Ricardo Tostes Gazzinelli, Oscar Bruna-Romero, Pedro Luiz Menin Ruiz, Daniel Araki Ribeiro, Joseli Lannes-Vieira, Marcela de Freitas Lopes, Mauricio Martins Rodrigues, José Ronnie Carvalho de Vasconcelos
Integrins mediate the lymphocyte migration into an infected tissue, and these cells are essential for controlling the multiplication of many intracellular parasites such as Trypanosoma cruzi, the causative agent of Chagas disease. Here, we explore LFA-1 and VLA-4 roles in the migration of specific CD8+ T cells generated by heterologous prime-boost immunization during experimental infection with T. cruzi. To this end, vaccinated mice were treated with monoclonal anti-LFA-1 and/or anti-VLA-4 to block these molecules...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29075657/impaired-t-cell-migration-to-the-cns-under-fingolimod-and-dimethyl-fumarate
#16
Amandine Mathias, Sylvain Perriot, Mathieu Canales, Claudia Blatti, Coline Gaubicher, Myriam Schluep, Britta Engelhardt, Renaud Du Pasquier
OBJECTIVE: To evaluate the long-term effects of treatments used in MS on the T-cell trafficking profile. METHODS: We enrolled 83 patients with MS under fingolimod (FTY), natalizumab (NTZ), dimethyl fumarate (DMF), or other disease-modifying treatments (DMTs). Blood was drawn before treatment onset and up to 36-48 months. The ex vivo expression of CNS-related integrins (α4β1 and αL subunit of LFA-1) and the gut-related integrin (α4β7) was assessed using flow cytometry on CD4+ and CD8+ T cells...
November 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28972539/cd56bright-nk-cells-exhibit-potent-antitumor-responses-following-il-15-priming
#17
Julia A Wagner, Maximillian Rosario, Rizwan Romee, Melissa M Berrien-Elliott, Stephanie E Schneider, Jeffrey W Leong, Ryan P Sullivan, Brea A Jewell, Michelle Becker-Hapak, Timothy Schappe, Sara Abdel-Latif, Aaron R Ireland, Devika Jaishankar, Justin A King, Ravi Vij, Dennis Clement, Jodie Goodridge, Karl-Johan Malmberg, Hing C Wong, Todd A Fehniger
NK cells, lymphocytes of the innate immune system, are important for defense against infectious pathogens and cancer. Classically, the CD56dim NK cell subset is thought to mediate antitumor responses, whereas the CD56bright subset is involved in immunomodulation. Here, we challenge this paradigm by demonstrating that brief priming with IL-15 markedly enhanced the antitumor response of CD56bright NK cells. Priming improved multiple CD56bright cell functions: degranulation, cytotoxicity, and cytokine production...
November 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28954823/a-novel-intracellular-pool-of-lfa-1-is-critical-for-asymmetric-cd8-t-cell-activation-and-differentiation
#18
Tara Capece, Brandon L Walling, Kihong Lim, Kyun-Do Kim, Seyeon Bae, Hung-Li Chung, David J Topham, Minsoo Kim
The integrin lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) is a key T cell adhesion receptor that mediates stable interactions with antigen-presenting cell (APC), as well as chemokine-mediated migration. Using our newly generated CD11a-mYFP knock-in mice, we discovered that naive CD8(+) T cells reserve a significant intracellular pool of LFA-1 in the uropod during migration. Intracellular LFA-1 quickly translocated to the cell surface with antigenic stimulus. Importantly, the redistribution of intracellular LFA-1 at the contact with APC was maintained during cell division and led to an unequal inheritance of LFA-1 in divided T cells...
November 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28945328/inactivated-sendai-virus-particles-upregulate-cancer-cell-icam-1-expression-with-enhancing-nk-cell-sensitivity-on-cancer-cell
#19
Simin Li, Tomoyuki Nishikawa, Yasufumi Kaneda
We have already reported that the inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) has multiple anti-cancer effects, including induction of cancer-selective cell death and activation of anti-cancer immunity. HVJ-E stimulates dendritic cells (DCs) to produce cytokines and chemokines such as IFN-β, IL-6, CCL5 and CXCL10, which activate both CD8(+) T cells and NK cells and recruit them to the tumor microenvironment. However, the effect of HVJ-E on modulating the sensitivity of cancer cells to immune cell attack has yet to be investigated...
September 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28918491/dynamics-of-allosteric-modulation-of%C3%A2-lymphocyte-function-associated-antigen-1-closure-open-switch-unveiling-the-structural-mechanisms-associated-with-outside-in-signaling-activation
#20
Maryam Abdullahi, Fisayo A Olotu, Mahmoud E Soliman
OBJECTIVES: To provide insight into the dynamics of the shape-shifting mechanistic events associated with the opening (activation) of Lymphocyte Function Associated Antigen-1 upon allosteric modulation by an activator, ICAM Binding Enhancer-667 (IBE-667), using molecular dynamics simulation. RESULTS: Various parameters were used to appropriately describe and understand the sequence of events that characterized its activation across the simulation period such as residual distances, TriCα angles; as well as the dihedral angle...
September 16, 2017: Biotechnology Letters
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