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https://www.readbyqxmd.com/read/28203119/higher-phagocytic-activity-of-thioglycollate-elicited-peritoneal-macrophages-is-related-to-metabolic-status-of-the-cells
#1
Sofia Pavlou, Luxi Wang, Heping Xu, Mei Chen
BACKGROUND: Peritoneal macrophages are widely used in immunological studies. The cells can be collected under non-elicited (resident) or elicited (e.g., with Brewer thioglycollate broth injection) conditions, and their phenotype and functions differ. Recent studies have shown that macrophage phenotype and function are related to their metabolic states, and metabolic reprogramming has been an emerging concept for controlling macrophage function. In this study, we examined the metabolic state of resident and elicited macrophages and investigated how their metabolic state may affect cell function, including phagocytosis...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28159748/estradiol-promotes-breast-cancer-cell-migration-via-recruitment-and-activation-of-neutrophils
#2
Gabriela Vazquez Rodriguez, Annelie Abrahamsson, Lasse Dahl Ejby Jensen, Charlotta Dabrosin
Estradiol (E2) plays a key role in breast cancer progression. Most breast cancer recurrences express the estrogen receptor (ER), but nearly 50% of patients are resistant to anti-estrogen therapy. Novel therapeutic targets of ER positive breast cancers are needed. Protumoral neutrophils expressing the lymphocyte function-associated antigen 1 (LFA-1) integrin may mediate cancer metastasis and transforming growth factor β1 (TGFβ1) is the major chemoattractant for neutrophils. The role of E2 in neutrophil-ER+ breast cancer cell interactions is unknown...
February 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28137909/ndr1-dependent-regulation-of-kindlin-3-controls-high-affinity-lfa-1-binding-and-immune-synapse-organization
#3
Naoyuki Kondo, Yoshihiro Ueda, Toshiyuki Kita, Madoka Ozawa, Takashi Tomiyama, Kaneki Yasuda, Dae-Sik Lim, Tatsuo Kinashi
Antigen-specific adhesion between T cells and antigen-presenting cells (APC) during the formation of the immunological synapse (IS) is mediated by LFA-1 and ICAM-1. Herein, LFA-1/ICAM-1 interactions were measured at the single-molecule level on supported lipid bilayers. High-affinity binding was detected at low frequencies in the inner peripheral supramolecular activation cluster (SMAC) zone that contained high levels of activated Rap1 and kindlin-3. Rap1 was essential for T cell attachment, whereas deficiencies of ste20-like kinases, Mst1/Mst2 diminished high-affinity binding, and abrogated central SMAC formation with mislocalized kindlin-3 and vesicle transport regulators involved in TCR recycling/releasing machineries, resulting in impaired T-APC interactions...
January 30, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28122813/hs1-deficiency-impairs-neutrophil-recruitment-in-vivo-and-activation-of-the-small-gtpases-rac1-and-rap1
#4
Joanna Latasiewicz, Annette Artz, Ding Jing, Mariana Pacheco Blanco, Silke M Currie, Martha Velázquez Avila, Michael Schnoor, Dietmar Vestweber
Neutrophil extravasation is a critical step of the innate immune system's response to inflammation. This multistep process is tightly regulated by adhesion and signaling molecules in the endothelium and neutrophils. Activation of the β2 integrin LFA-1 is critical for adhesion of leukocytes to postcapillary venules. This step requires coordinated activation of signaling pathways in chemokine-stimulated neutrophils, including GTPase activation and cytoskeletal remodeling, leading to conformational changes in LFA-1...
January 25, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28122237/t-cell-migration-from-inflamed-skin-to-draining-lymph-nodes-requires-intralymphatic-crawling-supported-by-icam-1-lfa-1-interactions
#5
Alvaro Teijeira, Morgan C Hunter, Erica Russo, Steven T Proulx, Thomas Frei, Gudrun F Debes, Marc Coles, Ignacio Melero, Michael Detmar, Ana Rouzaut, Cornelia Halin
T cells are the most abundant cell type found in afferent lymph, but their migration through lymphatic vessels (LVs) remains poorly understood. Performing intravital microscopy in the murine skin, we imaged T cell migration through afferent LVs in vivo. T cells entered into and actively migrated within lymphatic capillaries but were passively transported in contractile collecting vessels. Intralymphatic T cell number and motility were increased during contact-hypersensitivity-induced inflammation and dependent on ICAM-1/LFA-1 interactions...
January 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/28100681/lfa-1-activation-in-nk-cells-and-their-subsets-influence-of-receptors-maturation-and-cytokine-stimulation
#6
Doris Urlaub, Kristine Höfer, Martha-Lena Müller, Carsten Watzl
The integrin LFA-1 is essential for efficient activation and for cytotoxicity of NK cells because it initiates the assembly of the immunological synapse and mediates firm adhesion to the target. LFA-1 is also needed to polarize the cytotoxic machinery of the NK cell toward the target cell. The binding affinity and avidity of integrins can be regulated via inside-out signals from other receptors. In this article, we investigate the signals necessary to activate LFA-1 in human NK cells. Our data show that LFA-1 has a low ligand-binding activity in resting human NK cells, but it can be stimulated by triggering activating receptors, such as 2B4 or CD16, or by coactivation of different receptor combinations...
January 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28098193/non-pathogenic-tissue-resident-cd8-t-cells-uniquely-accumulate-in-the-brains-of-lupus-prone-mice
#7
Peter A Morawski, Chen-Feng Qi, Silvia Bolland
Severe lupus often includes psychiatric and neurological sequelae, although the cellular contributors to CNS disease remain poorly defined. Using intravascular staining to discriminate tissue-localized from blood-borne cells, we find substantial accumulation of CD8(+) T cells relative to other lymphocytes in brain tissue, which correlates with lupus disease and limited neuropathology. This is in contrast to all other affected organs, where infiltrating CD4(+) cells are predominant. Brain-infiltrating CD8(+) T cells represent an activated subset of those found in the periphery, having a resident-memory phenotype (CD69(+)CD122(-)PD1(+)CD44(+)CD62L(-)) and expressing adhesion molecules (VLA-4(+)LFA-1(+)) complementary to activated brain endothelium...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077302/neutrophil-adhesion-and-crawling-dynamics-on-liver-sinusoidal-endothelial-cells-under-shear-flow
#8
Hao Yang, Ning Li, Yu Du, Chunfang Tong, Shouqin Lü, Jinrong Hu, Yan Zhang, Mian Long
Neutrophil (polymorphonuclear leukocyte, PMN) recruitment in the liver sinusoid takes place in almost all liver diseases and contributes to pathogen clearance or tissue damage. While PMN rolling unlikely appears in liver sinusoids and Mac-1 or CD44 is assumed to play respective roles during in vivo local or systematic inflammatory stimulation, the regulating mechanisms of PMN adhesion and crawling dynamics are still unclear from those in vivo studies. Here we developed a two-dimensional in vitro sinusoidal model with primary liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs) to investigate TNF-α-induced PMN recruitment under shear flow...
January 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28066794/altered-monocyte-and-endothelial-cell-adhesion-molecule-expression-is-linked-to-vascular-inflammation-in-human-immunodeficiency-virus-infection
#9
Manjusha Kulkarni, Emily Bowman, Janelle Gabriel, Taylor Amburgy, Elizabeth Mayne, David A Zidar, Courtney Maierhofer, Abigail Norris Turner, Jose A Bazan, Susan L Koletar, Michael M Lederman, Scott F Sieg, Nicholas T Funderburg
BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals have increased risk for vascular thrombosis, potentially driven by interactions between activated leukocytes and the endothelium. METHODS: Monocyte subsets (CD14(+)CD16(-), CD14(+)CD16(+), CD14(Dim)CD16(+)) from HIV negative (HIV(-)) and antiretroviral therapy-treated HIV positive (HIV(+)) participants (N = 19 and 49) were analyzed by flow cytometry for adhesion molecule expression (lymphocyte function-associated antigen 1 [LFA-1], macrophage-1 antigen [Mac-1], CD11c/CD18, very late antigen [VLA]-4) and the fractalkine receptor (CX3CR1); these receptors recognize ligands (intercellular adhesion molecules [ICAMs], vascular cell adhesion molecule [VCAM]-1, fractalkine) on activated endothelial cells (ECs) and promote vascular migration...
October 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28058622/lifitegrast-ophthalmic-solution-5-a-review-in-dry-eye-disease
#10
Gillian M Keating
Lifitegrast is a novel small molecule integrin antagonist that blocks the binding of intercellular adhesion molecule 1 (ICAM-1) to lymphocyte function-associated antigen 1 (LFA-1). Lifitegrast ophthalmic solution 5% (Xiidra™) was recently approved in the USA for the treatment of dry eye disease. The efficacy of lifitegrast ophthalmic solution 5% was compared with vehicle in a 12-week phase 2 study and three 12-week phase 3 studies (OPUS-1, OPUS-2 and OPUS-3) in patients with dry eye disease. Taken as a whole, results of these trials support the treatment effect of lifitegrast ophthalmic solution 5% in improving a symptom of dry eye disease (i...
February 2017: Drugs
https://www.readbyqxmd.com/read/28052935/d120-and-k152-within-the-ph-domain-of-t-cell-adapter-skap55-regulate-plasma-membrane-targeting-of-skap55-and-lfa-1-affinity-modulation-in-human-t-lymphocytes
#11
Amelie Witte, Bernhard Meineke, Jana Sticht, Lars Philipsen, Benno Kuropka, Andreas J Müller, Christian Freund, Burkhart Schraven, Stefanie Kliche
The β2-integrin lymphocyte function-associated antigen-1 (LFA-1) is needed for T cell receptor (TCR) induced activation of LFA-1 to promote T cell adhesion and interaction with antigen presenting cells (APCs). LFA-1-mediated cell-cell interactions are critical for proper T cell differentiation and proliferation. The Src Kinase-Associated Phosphoprotein of 55 kDa (SKAP55) is a key regulator of TCR-mediated LFA-1 signaling (inside-out/outside-in signaling). To gain understanding of how SKAP55 controls TCR-mediated LFA-1 activation, we assessed the functional role of its Pleckstrin Homology (PH) domain...
January 4, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28003439/prolonged-exposure-to-volatile-anesthetic-isoflurane-worsens-the-outcome-of-polymicrobial-abdominal-sepsis
#12
Sophia Koutsogiannaki, Matthew M Schaefers, Toshiaki Okuno, Mai Ohba, Takehiko Yokomizo, Gregory P Priebe, James A DiNardo, Soriano G Sulpicio, Koichi Yuki
Sepsis continues to result in high morbidity and mortality. General anesthesia is often administered to septic patients, but the impacts of general anesthesia on host defense are not well understood. General anesthesia can be given by volatile and intravenous anesthetics. Our previous in vitro study showed that volatile anesthetic isoflurane directly inhibits leukocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1), critical adhesion molecules on leukocytes. Thus, the role of isoflurane exposure on in vivo LFA-1 and Mac-1 function was examined using polymicrobial abdominal sepsis model in mice...
December 20, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27986909/sos1-arhgef1-and-dock2-rho-gefs-mediate-jak-dependent-lfa-1-activation-by-chemokines
#13
Lara Toffali, Alessio Montresor, Michela Mirenda, Giorgio Scita, Carlo Laudanna
JAK-dependent activation of the rho module of integrin affinity triggering mediates chemokine-induced leukocyte adhesion. However, the signaling events linking JAKs to rho small GTPase activation by chemokines is still incompletely described. In this study, we show that son of sevenless 1 (SOS1), rho guanine nucleotide exchange factor (GEF)1 (ARHGEF1), and dedicator of cytokinesis (DOCK)2 GEFs mediate CXCL12-induced LFA-1 activation in human primary T lymphocytes. Downregulated expression of SOS1, ARHGEF1, and DOCK2 impairs LFA-1-mediated rapid T lymphocyte adhesion as well as underflow arrest on ICAM-1 induced by CXCL12...
December 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27965383/defects-in-cd4-t-cell-lfa-1-integrin-dependent-adhesion-and-proliferation-protect-cd47-mice-from-eae
#14
Veronica Azcutia, Ribal Bassil, Jan M Herter, Daniel Engelbertsen, Gail Newton, Anu Autio, Tanya Mayadas, Andrew H Lichtman, Samia J Khoury, Charles A Parkos, Wassim Elyaman, Francis W Luscinskas
CD47 is known to play an important role in CD4(+) T cell homeostasis. We recently reported a reduction in mice deficient in the Cd47 gene (Cd47(-/-)) CD4(+) T cell adhesion and transendothelial migration (TEM) in vivo and in vitro as a result of impaired expression of high-affinity forms of LFA-1 and VLA-4 integrins. A prior study concluded that Cd47(-/-) mice were resistant to experimental autoimmune encephalomyelitis (EAE) as a result of complete failure in CD4(+) T cell activation after myelin oligodendrocyte glycoprotein peptide 35-55 aa (MOG35-55) immunization...
December 13, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27956903/comprehensive-screening-of-cell-surface-markers-expressed-by-adult-derived-human-liver-stem-progenitor-cells-harvested-at-passage-5-potential-implications-for-engraftment
#15
Pierre-Edouard Dollet, Joachim Ravau, Floriane André, Mustapha Najimi, Etienne Sokal, Catherine Lombard
Mesenchymal stromal cells (MSCs) are known to have potential therapeutic benefits for a number of diseases. However, many studies report low engraftment levels, regardless of the target organ. One possible explanation could be that MSCs do not express the necessary receptors for engraftment. Indeed, MSCs appear to use a similar mechanism to leukocytes to engraft into injured organs, relying on various receptors for rolling, firm adhesion, and transmigration. In this study, we conducted an extensive surface molecule screening of adult-derived human liver stem/progenitor cells (ADHLSC) in an attempt to shed some light on this subject...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27941787/recruitment-of-calcineurin-to-the-tcr-positively-regulates-t-cell-activation
#16
Debjani Dutta, Valarie A Barr, Itoro Akpan, Paul R Mittelstadt, Laishram I Singha, Lawrence E Samelson, Jonathan D Ashwell
Calcineurin is a phosphatase whose primary targets in T cells are NFAT transcription factors, and inhibition of calcineurin activity by treatment with cyclosporin A (CsA) or FK506 is a cornerstone of immunosuppressive therapies. Here we found that calcineurin was recruited to the T cell antigen receptor (TCR) signaling complex, where it reversed inhibitory phosphorylation of the tyrosine kinase Lck on Ser59 (Lck(S59)). Loss of calcineurin activity impaired phosphorylation of Tyr493 of the tyrosine kinase ZAP-70 (ZAP-70(Y493)), as well as some downstream pathways in a manner consistent with signaling in cells expressing Lck(S59A) (Lck that cannot be phosphorylated) or Lck(S59E) (a phosphomimetic mutant)...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/27940100/the-effect-of-different-anesthetics-on-tumor-cytotoxicity-by-natural-killer-cells
#17
Kazumasa Tazawa, Sophia Koutsogiannaki, Matthew Chamberlain, Koichi Yuki
A number of retrospective studies have suggested that choice of anesthetic drugs during surgical tumor resection might affect tumor recurrence/metastasis, or outcome of patients. The recent study showed that volatile anesthetics-based general anesthesia was associated with the worse outcomes than intravenous anesthetics-based general anesthesia. However, the underlying mechanism is yet to be determined. Because natural killer (NK) cells are implicated as important immune cells for tumor recurrence/metastasis in the perioperative period, we examined the effect of different anesthetics on NK cell-mediated tumor cytotoxicity...
January 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/27915019/the-impact-of-cell-surface-pegylation-and-short-course-immunotherapy-on-islet-graft-survival-in-an-allogeneic-murine-model
#18
Jaime A Giraldo, R Damaris Molano, Hernán R Rengifo, Carmen Fotino, Kerim M Gattás-Asfura, Antonello Pileggi, Cherie L Stabler
: Islet transplantation is a promising therapy for Type 1 diabetes mellitus; however, host inflammatory and immune responses lead to islet dysfunction and destruction, despite potent systemic immunosuppression. Grafting of poly(ethylene glycol) (PEG) to the periphery of cells or tissues can mitigate inflammation and immune recognition via generation of a steric barrier. Herein, we sought to evaluate the complementary impact of islet PEGylation with a short-course immunotherapy on the survival of fully-MHC mismatched islet allografts (DBA/2 islets into diabetic C57BL/6J recipients)...
February 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/27907215/cd8-t-cells-induce-fatal-brainstem-pathology-during-cerebral-malaria-via-luminal-antigen-specific-engagement-of-brain-vasculature
#19
Phillip A Swanson, Geoffrey T Hart, Matthew V Russo, Debasis Nayak, Takele Yazew, Mirna Peña, Shahid M Khan, Chris J Janse, Susan K Pierce, Dorian B McGavern
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection that results in thousands of deaths each year, mostly in African children. The in vivo mechanisms underlying this fatal condition are not entirely understood. Using the animal model of experimental cerebral malaria (ECM), we sought mechanistic insights into the pathogenesis of CM. Fatal disease was associated with alterations in tight junction proteins, vascular breakdown in the meninges / parenchyma, edema, and ultimately neuronal cell death in the brainstem, which is consistent with cerebral herniation as a cause of death...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27906544/lfa-1-icam-1-interaction-as-a-therapeutic-target-in-dry-eye-disease
#20
Stephen C Pflugfelder, Michael Stern, Steven Zhang, Amir Shojaei
Dry eye disease (DED) is a common ocular disorder associated with inflammation of the lacrimal gland and ocular surface. The interaction of the integrin lymphocyte function-associated antigen-1 (LFA-1) with its cognate ligand intercellular adhesion molecule-1 (ICAM-1) is known to have important roles in the interaction of a variety of cells involved in immune responses and inflammation, including those prominent in ocular surface inflammation. Lifitegrast, an LFA-1 antagonist that blocks binding of ICAM-1 to LFA-1, has recently been approved in the United States for the treatment of signs and symptoms of DED...
January 2017: Journal of Ocular Pharmacology and Therapeutics
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