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https://www.readbyqxmd.com/read/29774029/lfa-1-in-t-cell-migration-and-differentiation
#1
REVIEW
Brandon L Walling, Minsoo Kim
Maintenance of homeostatic immune surveillance and development of effective adaptive immune responses require precise regulation of spatial and temporal lymphocyte trafficking throughout the body to ensure pathogen clearance and memory generation. Dysregulation of lymphocyte activation and migration can lead to impaired adaptive immunity, recurrent infections, and an array of autoimmune diseases and chronic inflammation. Central to the recruitment of T cells, integrins are cell surface receptors that regulate adhesion, signal transduction, and migration...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29765373/compartmentalized-cyclic-amp-production-by-the-bordetella-pertussis-and-bacillus-anthracis-adenylate-cyclase-toxins-differentially-affects-the-immune-synapse-in-t-lymphocytes
#2
Vijay B Arumugham, Cristina Ulivieri, Anna Onnis, Francesca Finetti, Fiorella Tonello, Daniel Ladant, Cosima T Baldari
A central feature of the immune synapse (IS) is the tight compartmentalization of membrane receptors and signaling mediators that is functional for its ability to coordinate T cell activation. Second messengers centrally implicated in this process, such as Ca2+ and diacyl glycerol, also undergo compartmentalization at the IS. Current evidence suggests a more complex scenario for cyclic AMP (cAMP), which acts both as positive and as negative regulator of T-cell antigen receptor (TCR) signaling and which, as such, must be subjected to a tight spatiotemporal control to allow for signaling at the IS...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755616/histological-and-immunological-characteristics-of-the-junctional-epithelium
#3
REVIEW
Masanori Nakamura
The continuity of epithelial tissue is collapsed by tooth eruption. The junctional epithelium (JE) is attached to the tooth surface by hemidesmosomes, which constitutes the front-line defense against periodontal bacterial infection. JE constitutively expresses intercellular adhesion molecule-1 (ICAM-1), and neutrophils and lymphocytes penetrate into JE via interaction between ICAM-1 and LFA-1 expressed on the surface of these migrating cells. JE also expresses cytokines and chemokines. These functions of JE are maintained even in germ-free condition...
May 2018: Japanese Dental Science Review
https://www.readbyqxmd.com/read/29742342/receptor-based-peptides-for-inhibition-of-rtx-leukotoxin-ltxa-activity
#4
Eric Krueger, Shannon Hayes, En Hyung Chang, Shailagne Yutuc, Angela C Brown
The Gram-negative bacterium Aggregatibacter actinomycetemcomitans, commonly associated with localized aggressive periodontitis (LAP), secretes an RTX (repeats-in-toxin) protein leukotoxin (LtxA) that targets human white blood cells, an interaction that is driven by its recognition of the lymphocyte function-associated antigen-1 (LFA-1) integrin. In this study, we report on the inhibition of LtxA-LFA-1 binding as an anti-virulence strategy to inhibit LtxA-mediated cytotoxicity. Specifically, we designed and synthesized peptides corresponding to the reported LtxA binding domain on LFA-1 and characterized their capability to inhibit LtxA binding to LFA-1 and subsequent cytotoxic activity in human immune cells...
May 9, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29730712/homing-genes-expression-in-fucosyltransferase-vi-treated-umbilical-cord-blood-cd133-cells-which-expanded-on-protein-coated-nanoscaffolds
#5
Amir Atashi, Maryam Islami, Yousef Mortazavi, Masoud Soleimani
Umbilical cord blood (UCB)-derived hematopoietic stem cells (HSCs) are considered because of their self-renewing, differentiating, proliferating, and readily available properties. Moreover, HSCs' homing to the hematopoietic microenvironment is an important step in their transplantation process. But low content of progenitor cells in one unit of UCB and defect in the bone marrow (BM) homing limit their applications. Hence, we decided to correct this deficiency with ex vivo incubation of CD133+ cells using fucosyltransferase VI and GDP-fucose...
May 5, 2018: Molecular Biotechnology
https://www.readbyqxmd.com/read/29729315/icam3-mediates-tumor-metastasis-via-a-lfa-1-icam3-erm-dependent-manner
#6
Wenzhi Shen, Xiaoyuan Zhang, Renle Du, Yan Fan, Dehong Luo, Yonghua Bao, Wancai Yang, Na Luo, Yunping Luo, Shuangtao Zhao
ICAM3 was reported to promote metastasis in tumors. However, the underlying mechanism remains elusive. Here, we disclosed that the expression of ICAM3 was closely correlated with the TNM stage of human breast and lung cancer, as well as the dominant overexpression in high aggressive tumor cell lines (231 and A549 cells). Moreover, the knockdown of ICAM3 inhibited tumor metastasis whereas the ectopic expression of ICAM3 promoted tumor metastasis both in vitro and in vivo. In addition, exploration of the underlying mechanism demonstrated that ICAM3 not only binds to LFA-1 with its extracellular domain and structure protein ERM but also to lamellipodia with its intracellular domain which causes a tension that pulls cells apart (metastasis)...
May 2, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29712775/the-itim-domain-containing-nk-receptor-ly49q-impacts-pulmonary-infection-by-mediating-neutrophil-functions
#7
Andreas Margraf, Stephanie Volmering, Jennifer Skupski, Veerle Van Marck, Andrew P Makrigiannis, Helena Block, Alexander Zarbock
Pulmonary infection is a frequent pathology associated with excessive neutrophil infiltration. Ly49Q, an ITIM domain-bearing receptor expressed on different leukocytes, has been recently reported to impact neutrophil migration and polarization. Utilizing a murine model of Klebsiella pneumoniae- induced pulmonary infection in combination with additional in vivo and in vitro assays, we show that Ly49Q is critically involved in different steps of the leukocyte adhesion cascade. Ly49Q deficiency is associated with a reduced rolling velocity, impaired crawling capacity, and diminished transmigration...
April 30, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29699851/blockade-of-adhesion-molecule-lymphocyte-function-associated-antigen-1-improves-long-term-heart-allograft-survival-in-mixed-chimeras
#8
Nina Pilat, Philipp Sabler, Christoph Klaus, Benedikt Mahr, Lukas Unger, Karin Hock, Mario Wiletel, Christoph Schwarz, Ivan Kristo, Heinz Regele, Thomas Wekerle
BACKGROUND: The mixed chimerism approach for intentional induction of donor-specific tolerance was shown to be successful in various models from mice to humans. For transplant patients, the approach would obviate the need for long-term immunosuppression and associated side effects; moreover, it would preclude the risk of late graft loss due to chronic rejection. Widespread clinical application is hindered by toxicities related to recipient pre-conditioning. Herein we aimed to investigate a clinically relevant protocol for tolerance induction to cardiac allografts, sparing CD40 blockade or T-cell depletion...
March 30, 2018: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29662864/expression-of-adhesion-molecules-on-cd34-cells-from-steady-state-bone-marrow-before-and-after-mobilization-and-their-association-with-the-yield-of-cd34-cells
#9
Karin Zattar Cecyn, Eliza Y S Kimura, Dulce Marta S M Lima, Miyoko Yamamoto, José Orlando Bordin, José Salvador R de Oliveira
Background: Cell adhesion molecules (CAMs) expressed on hematopoietic progenitor cells (HPCs), endothelial cells, and stromal cells play a pivotal role in the mobilization of CD34+ cells. Herein, we conducted a non-randomized peripheral blood stem cell (PBSC) mobilization study aimed to compare the potential differences in the expressions of several CAMs and chemokines on CD34+ cells obtained from bone marrow aspirate before and after HPC mobilization from patients with hematologic malignancies and healthy donors...
March 2018: Blood Research
https://www.readbyqxmd.com/read/29604893/forced-rupture-of-cell-adhesion-complexes-reveals-abrupt-switch-between-two-brittle-states
#10
Ngo Minh Toan, D Thirumalai
Cell adhesion complexes (CACs), which are activated by ligand binding, play key roles in many cellular functions ranging from cell cycle regulation to mediation of cell extracellular matrix adhesion. Inspired by single molecule pulling experiments using atomic force spectroscopy on leukocyte function-associated antigen-1 (LFA-1), expressed in T-cells, bound to intercellular adhesion molecules (ICAM), we performed constant loading rate (rf ) and constant force (F) simulations using the self-organized polymer model to describe the mechanism of ligand rupture from CACs...
March 28, 2018: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29572116/effect-of-irradiation-induced-intercellular-adhesion-molecule-1-expression-on-natural-killer-cell-mediated-cytotoxicity-toward-human-cancer-cells
#11
Jae-Uk Jeong, Tung Nguyen Thanh Uong, Woong-Ki Chung, Taek-Keun Nam, Sung-Ja Ahn, Ju-Young Song, Sang-Ki Kim, Dong-Jun Shin, Eugene Cho, Kyoung Won Kim, Duck Cho, Mee Sun Yoon
BACKGROUND AIMS: Irradiation enhances the adhesion between natural killer (NK) cells and target cells by up-regulating intercellular adhesion molecule-1 (ICAM-1) on target cells. Therefore, we investigated the effect of irradiation-induced ICAM-1 expression on human cancer cells on NK cell-mediated cytotoxicity. METHODS: Expression levels of ICAM-1 on the target cell surface before and after irradiation of six human cancer cell lines (HL60, SKBR-3, T47D, HCT-116, U937 and U251) were analyzed by flow cytometry...
March 20, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29546034/the-immunological-regulation-roles-of-porcine-%C3%AE-1-4-galactosyltransferase-v-b4galt5-in-prrsv-infection
#12
Lei Zhang, Jie Ren, Peidian Shi, Dong Lu, Chengxue Zhao, Yanxin Su, Lilin Zhang, Jinhai Huang
B4GALT5, also known as β-1, 4 galactosyltransferase V, is one of the members of β-1, 4 galactosyltransferase gene (B4GALT) family, which was concerned with embryonic development, tumor generation, other malignant diseases. In this study, we firstly cloned porcine B4GALT (pB4GALT5) from porcine alveolar macrophages, and predicted the structural domain and function of seven porcine β-1, 4 galactosyltransferase (I-VII) based on transcriptome analysis of PRRSV infected cells. Additionally, the upregulated porcine B4GALT5 expression was detected from PRRSV infected porcine alveolar macrophage (PAM) cells...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29545805/centrosome-and-golgi-localized-protein-kinase-n-associated-protein-serves-as-a-docking-platform-for-protein-kinase-a-signaling-and-microtubule-nucleation-in-migrating-t-cells
#13
Seow Theng Ong, Madhavi Latha Somaraju Chalasani, M H U Turabe Fazil, Praseetha Prasannan, Atish Kizhakeyil, Graham D Wright, Dermot Kelleher, Navin Kumar Verma
Centrosome- and Golgi-localized protein kinase N-associated protein (CG-NAP), also known as AKAP450, is a cytosolic scaffolding protein involved in the targeted positioning of multiple signaling molecules, which are critical for cellular functioning. Here, we show that CG-NAP is predominantly expressed in human primary T-lymphocytes, localizes in close proximity (<0.2 μm) with centrosomal and Golgi structures and serves as a docking platform for Protein Kinase A (PKA). GapmeR-mediated knockdown of CG-NAP inhibits LFA-1-induced T-cell migration and impairs T-cell chemotaxis toward the chemokine SDF-1α...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29536351/imaging-of-atherosclerosis-targeting-lfa-1-on-inflammatory-cells-with-111-in-danbirt
#14
E J Meester, B J Krenning, R H de Blois, J P Norenberg, M de Jong, M R Bernsen, K Van der Heiden
BACKGROUND: 111 In-DOTA-butylamino-NorBIRT (DANBIRT) is a novel radioligand which binds to Leukocyte Function-associated Antigen-1 (LFA-1), expressed on inflammatory cells. This study evaluated111 In-DANBIRT for the visualization of atherosclerotic plaque inflammation in mice. METHODS AND RESULTS: ApoE-/- mice, fed an atherogenic diet up to 20 weeks (n = 10), were imaged by SPECT/CT 3 hours post injection of111 In-DANBIRT (~ 200 pmol, ~ 40 MBq). Focal spots of111 In-DANBIRT were visible in the aortic arch of all animals, with an average Target-to-Background Ratio (TBR) of 1...
March 13, 2018: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
https://www.readbyqxmd.com/read/29507098/ligand-and-cation-induced-structural-alterations-of-the-leukocyte-integrin-lfa-1
#15
Mehmet Sen, Adem C Koksal, Koichi Yuki, Jianchuan Wang, Timothy A Springer
In αI integrins, including leukocyte function-associated antigen 1 (LFA-1), ligand-binding function is delegated to the αI domain, requiring extra steps in the relay of signals that activate ligand binding and coordinate it with cytoplasmic signals. Crystal structures reveal great variation in orientation between the αI domain and the remainder of the integrin head. Here, we investigated the mechanisms involved in signal relay to the αI domain, including whether binding of the ligand intercellular adhesion molecule-1 (ICAM-1) to the αI domain is linked to headpiece opening and engenders a preferred αI domain orientation...
April 27, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29500453/sophora-flavescens-protects-against-mycobacterial-trehalose-dimycolate-induced-lung-granuloma-by-inhibiting-inflammation-and-infiltration-of-macrophages
#16
Dehua Liu, Ben Chung-Lap Chan, Ling Cheng, Miranda Sin-Man Tsang, Jing Zhu, Chun-Wai Wong, Delong Jiao, Helen Yau-Tsz Chan, Ping Chung Leung, Christopher Wai-Kei Lam, Chun Kwok Wong
The immune system responds to Mycobacterium tuberculosis (MTB) infection by forming granulomas to quarantine the bacteria from spreading. Granuloma-mediated inflammation is a cause of lung destruction and disease transmission. Sophora flavescens (SF) has been demonstrated to exhibit bactericidal activities against MTB. However, its immune modulatory activities on MTB-mediated granulomatous inflammation have not been reported. In the present study, we found that flavonoids from Sophora flavescens (FSF) significantly suppressed the pro-inflammatory mediators released from mouse lung alveolar macrophages (MH-S) upon stimulation by trehalose dimycolate (TDM), the most abundant lipoglycan on MTB surface...
March 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29464004/biomimetic-nanoparticles-with-enhanced-affinity-towards-activated-endothelium-as-versatile-tools-for-theranostic-drug-delivery
#17
Jonathan O Martinez, Roberto Molinaro, Kelly A Hartman, Christian Boada, Roman Sukhovershin, Enrica De Rosa, Dickson Kirui, Shanrong Zhang, Michael Evangelopoulos, Angela M Carter, James A Bibb, John P Cooke, Ennio Tasciotti
Activation of the vascular endothelium is characterized by increased expression of vascular adhesion molecules and chemokines. This activation occurs early in the progression of several diseases and triggers the recruitment of leukocytes. Inspired by the tropism of leukocytes, we investigated leukocyte-based biomimetic nanoparticles (i.e., leukosomes) as a novel theranostic platform for inflammatory diseases. Methods : Leukosomes were assembled by combining phospholipids and membrane proteins from leukocytes...
2018: Theranostics
https://www.readbyqxmd.com/read/29453458/il-2-inducible-kinase-itk-is-critical-for-hiv-1-infection-of-jurkat-t-cells
#18
Anika Hain, Melanie Krämer, René M Linka, Saeideh Nakhaei-Rad, Mohammad Reza Ahmadian, Dieter Häussinger, Arndt Borkhardt, Carsten Münk
Successful replication of Human immunodeficiency virus (HIV)-1 depends on the expression of various cellular host factors, such as the interleukin-2 inducible T-cell kinase (ITK), a member of the protein family of TEC-tyrosine kinases. ITK is selectively expressed in T-cells and coordinates signaling pathways downstream of the T-cell receptor and chemokine receptors, including PLC-1 activation, Ca2+ -release, transcription factor mobilization, and actin rearrangements. The exact role of ITK during HIV-1 infection is still unknown...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29444440/measuring-integrin-conformational-change-on-the-cell-surface-with-super-resolution-microscopy
#19
Travis I Moore, Jesse Aaron, Teng-Leong Chew, Timothy A Springer
We use super-resolution interferometric photoactivation and localization microscopy (iPALM) and a constrained photoactivatable fluorescent protein integrin fusion to measure the displacement of the head of integrin lymphocyte function-associated 1 (LFA-1) resulting from integrin conformational change on the cell surface. We demonstrate that the distance of the LFA-1 head increases substantially between basal and ligand-engaged conformations, which can only be explained at the molecular level by integrin extension...
February 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29440406/chimeric-antigen-receptor-t-cells-form-nonclassical-and-potent-immune-synapses-driving-rapid-cytotoxicity
#20
A J Davenport, R S Cross, K A Watson, Y Liao, W Shi, H M Prince, P A Beavis, J A Trapani, M H Kershaw, D S Ritchie, P K Darcy, P J Neeson, M R Jenkins
Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters...
February 27, 2018: Proceedings of the National Academy of Sciences of the United States of America
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