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https://www.readbyqxmd.com/read/28727998/enrichment-of-endogenous-fractalkine-and-anti-inflammatory-cells-via-aptamer-functionalized-hydrogels
#1
Syed Faaiz Enam, Jack R Krieger, Tarun Saxena, Brian E Watts, Claire E Olingy, Edward A Botchwey, Ravi V Bellamkonda
Early recruitment of non-classical monocytes and their macrophage derivatives is associated with augmented tissue repair and improved integration of biomaterial constructs. A promising therapeutic approach to recruit these subpopulations is by elevating local concentrations of chemoattractants such as fractalkine (FKN, CX3CL1). However, delivering recombinant or purified proteins is not ideal due to their short half-lives, suboptimal efficacy, immunogenic potential, batch variabilities, and cost. Here we report an approach to enrich endogenous FKN, obviating the need for delivery of exogenous proteins...
July 10, 2017: Biomaterials
https://www.readbyqxmd.com/read/28723545/spineless-behavior-of-cx3cr1-monocytes-in-response-to-infection
#2
Paul A Muller, Daniel Mucida
Sickness in mammals can lead to cognition deficits, although the underlying mechanisms remain elusive. In a recent Nature Medicine article, Garré et al. (2017) report that sickness-induced cortical dendritic spine loss and impaired memory formation is mediated by CX3CR1(+) monocyte-derived TNF-α.
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28717419/platelet-extracellular-vesicles-induce-a-pro-inflammatory-smooth-muscle-cell-phenotype
#3
Tanja Vajen, Birke J Benedikter, Alexandra C A Heinzmann, Elena M Vasina, Yvonne Henskens, Martin Parsons, Patricia B Maguire, Frank R Stassen, Johan W M Heemskerk, Leon J Schurgers, Rory R Koenen
Extracellular vesicles (EVs) are mediators of cell communication during health and disease, and abundantly released by platelets upon activation or during ageing. Platelet EVs exert modulatory effects on immune and vascular cells. Platelet EVs may modulate the function of vascular smooth muscle cells (SMC). Platelet EVs were isolated from platelet-rich plasma and incubated with SMC in order to assess binding, proliferation, migration and pro-inflammatory phenotype of the cells. Platelet EVs firmly bound to resting SMC through the platelet integrin αIIbβ3, while binding also occurred in a CX3CL1-CX3CR1-dependent manner after cytokine stimulation...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28716963/chemokine-ccl2-ccr2-signaling-induces-neuronal-cell-death-via-stat3-activation-and-il-1%C3%AE-production-after-status-epilepticus
#4
Dai-Shi Tian, Jiyun Peng, Madhuvika Murugan, Lijie Feng, Jun-Li Liu, Ukpong B Eyo, Li-Jun Zhou, Rochelle Mogilevsky, Wei Wang, Long-Jun Wu
Elevated levels of chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 have been reported in patients with temporal lobe epilepsy and in experimental seizures. However, the functional significance and molecular mechanism underlying CCL2-CCR2 signaling in epileptic brain remains largely unknown. In this study, we found that the upregulated CCL2 was mainly expressed in hippocampal neurons and activated microglia from mice 1d after kainic acid (KA)-induced seizures. Taking advantage of CX3CR1(GFP/+):CCR2(RFP/+) double transgenic mice, we demonstrated that CCL2-CCR2 signaling participated in resident microglial activation and blood-derived monocyte infiltration...
July 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28696300/acetylcholine-producing-nk-cells-attenuate-cns-inflammation-via-modulation-of-infiltrating-monocytes-macrophages
#5
Wei Jiang, Daojing Li, Ranran Han, Chao Zhang, Wei-Na Jin, Kristofer Wood, Qiang Liu, Fu-Dong Shi, Junwei Hao
The nonneural cholinergic system of immune cells is pivotal for the maintenance of immunological homeostasis. Here we demonstrate the expression of choline acetyltransferase (ChAT) and cholinergic enzymes in murine natural killer (NK) cells. The capacity for acetylcholine synthesis by NK cells increased markedly under inflammatory conditions such as experimental autoimmune encephalomyelitis (EAE), in which ChAT expression escalated along with the maturation of NK cells. ChAT(+) and ChAT(-) NK cells displayed distinctive features in terms of cytotoxicity and chemokine/cytokine production...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28696256/a-novel-subset-of-anti-inflammatory-cd138-macrophages-is-deficient-in-mice-with-experimental-lupus
#6
Shuhong Han, Haoyang Zhuang, Stepan Shumyak, Jingfan Wu, Hui Li, Li-Jun Yang, Westley H Reeves
Dead cells accumulating in the tissues may contribute to chronic inflammation. We examined the cause of impaired apoptotic cell clearance in human and murine lupus. Dead cells accumulated in bone marrow from lupus patients but not from nonautoimmune patients undergoing myeloablation, where they were efficiently removed by macrophages (MΦ). Impaired apoptotic cell uptake by MΦ also was seen in mice treated i.p. with pristane (develop lupus) but not mineral oil (MO) (do not develop lupus). The inflammatory response to both pristane and MO rapidly depleted resident (Tim4(+)) large peritoneal MΦ...
July 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28696254/human-monocyte-subsets-are-transcriptionally-and-functionally-altered-in-aging-in-response-to-pattern-recognition-receptor-agonists
#7
Talibah U Metcalf, Peter A Wilkinson, Mark J Cameron, Khader Ghneim, Cindy Chiang, Anne M Wertheimer, John B Hiscott, Janko Nikolich-Zugich, Elias K Haddad
Age-related alterations in immunity have been linked to increased incidence of infections and decreased responses to vaccines in the aging population. Human peripheral blood monocytes are known to promote Ag presentation and antiviral activities; however, the impact of aging on monocyte functions remains an open question. We present an in-depth global analysis examining the impact of aging on classical (CD14(+)CD16(-)), intermediate (CD14(+)CD16(+)), and nonclassical (CD14(dim)CD16(+)) monocytes. Monocytes sorted from nonfrail healthy adults (21-40 y) and old (≥65 y) individuals were analyzed after stimulation with TLR4, TLR7/8, and retinoic acid-inducible gene I agonists...
July 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28691930/ly6clo-monocytes-drive-immunosuppression-and-confer-resistance-to-anti-vegfr2-cancer-therapy
#8
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/28687201/corrigendum-to-a-selective-cb2r-agonist-jwh133-restores-neuronal-circuit-after-germinal-matrix-hemorrhage-in-the-preterm-via-cx3cr1-microglia-neuropharm-119-2017-157-169
#9
Jun Tang, Hongping Miao, Bing Jiang, Qianwei Chen, Liang Tan, Yihao Tao, Jianbo Zhang, Fabao Gao, Hua Feng, Gang Zhu, Zhi Chen
No abstract text is available yet for this article.
July 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28683563/modulation-of-hematopoietic-lineage-specification-impacts-trem2-expression-in-microglia-like-cells-derived-from-human-stem-cells
#10
Peter J Amos, Susan Fung, Amanda Case, Jerusalem Kifelew, Leah Osnis, Carole L Smith, Kevin Green, Alipi Naydenov, Macarena Aloi, Jesse J Hubbard, Aravind Ramakrishnan, Gwenn A Garden, Suman Jayadev
Microglia are the primary innate immune cell type in the brain, and their dysfunction has been linked to a variety of central nervous system disorders. Human microglia are extraordinarily difficult to obtain for experimental investigation, limiting our ability to study the impact of human genetic variants on microglia functions. Previous studies have reported that microglia-like cells can be derived from human monocytes or pluripotent stem cells. Here, we describe a reproducible relatively simple method for generating microglia-like cells by first deriving embryoid body mesoderm followed by exposure to microglia relevant cytokines...
July 2017: ASN Neuro
https://www.readbyqxmd.com/read/28681650/safety-pharmacokinetics-and-efficacy-of-e6011-an-antifractalkine-monoclonal-antibody-in-a-first-in-patient-phase-1-2-study-on-rheumatoid-arthritis
#11
Yoshiya Tanaka, Tsutomu Takeuchi, Hisanori Umehara, Toshihiro Nanki, Nobuyuki Yasuda, Fumitoshi Tago, Makoto Kawakubo, Yasumi Kitahara, Seiichiro Hojo, Tetsu Kawano, Toshio Imai
OBJECTIVE: Fractalkine (CX3CL1/FKN) is a chemokine that regulates chemotaxis and adhesion of CX3C chemokine receptor 1 (CX3CR1)-expressing inflammatory cells. We conducted the first phase 1/2, open-label, multiple ascending dose study of E6011, a humanized anti-FKN monoclonal antibody, in Japanese rheumatoid arthritis (RA) patients (clinicaltrial.gov identifier: NCT02196558). METHODS: Active RA patients with an inadequate response or intolerance to methotrexate or tumor necrosis factor (TNF) inhibitor received E6011 at week 0, 1, 2, and thereafter every 2 weeks for 12 weeks...
July 6, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28680905/high-cellular-monocyte-activation-in-people-living-with-human-immunodeficiency-virus-on-combination-antiretroviral-therapy-and-lifestyle-matched-controls-is-associated-with-greater-inflammation-in-cerebrospinal-fluid
#12
Thijs Booiman, Ferdinand W Wit, Irma Maurer, Davide De Francesco, Caroline A Sabin, Agnes M Harskamp, Maria Prins, Paolo Garagnani, Chiara Pirazzini, Claudio Franceschi, Dietmar Fuchs, Magnus Gisslén, Alan Winston, Peter Reiss, Neeltje A Kootstra
BACKGROUND: Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). METHODS: A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation, intestinal damage, and inflammation in plasma and cerebrospinal fluid (CSF) of PLHIV with suppressed plasma viremia on combination antiretroviral therapy and age and demographically comparable HIV-negative individuals participating in the Comorbidity in Relation to AIDS (COBRA) cohort and, where appropriate, age-matched blood bank donors (BBD)...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28677375/high-expression-of-cx3c-chemokine-receptor-1-cx3cr1-in-human-carotid-plaques-is-associated-with-vulnerability-of-the-lesions
#13
Marta Masztalewicz, Przemysław Nowacki, Łukasz Szydłowski, Maciej Żukowski, Piotr Gutowski
<i><b>Introduction</b>: In data based on ex vivo studies and animal models, fractalkine is considered an important mediator in the development and destabilization of atherosclerotic plaques. We do not know how it is associated with human carotid plaques morphology. <b>Material and methods</b>: The study included 126 carotid plaques taken from 126 patients who underwent endarterectomy of internal carotid arteries. We assessed the following characteristics: inflammatory infiltration, connective tissue elements, foam cells, lipid core, plaque vascularisation, calcifications, intraplaque haemorrhage, thrombi built into the plaque structure, and mural thrombi...
2017: Folia Neuropathologica
https://www.readbyqxmd.com/read/28671693/transcriptomic-analysis-of-purified-human-cortical-microglia-reveals-age-associated-changes
#14
Thais F Galatro, Inge R Holtman, Antonio M Lerario, Ilia D Vainchtein, Nieske Brouwer, Paula R Sola, Mariana M Veras, Tulio F Pereira, Renata E P Leite, Thomas Möller, Paul D Wes, Mari C Sogayar, Jon D Laman, Wilfred den Dunnen, Carlos A Pasqualucci, Sueli M Oba-Shinjo, Erik W G M Boddeke, Suely K N Marie, Bart J L Eggen
Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes CX3CR1, P2RY12 and ITGAM (CD11B). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including TLR, Fcγ and SIGLEC receptors, as well as TAL1 and IFI16, regulators of proliferation and cell cycle...
July 3, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28666021/divergent-roles-for-ly6c-ccr2-cx3cr1-inflammatory-monocytes-during-primary-or-secondary-infection-of-the-skin-with-the-intra-phagosomal-pathogen-leishmania-major
#15
Audrey Romano, Matheus B H Carneiro, Nicole A Doria, Eric H Roma, Flavia L Ribeiro-Gomes, Ehud Inbar, Sang Hun Lee, Jonatan Mendez, Andrea Paun, David L Sacks, Nathan C Peters
Inflammatory monocytes can be manipulated by environmental cues to perform multiple functions. To define the role of monocytes during primary or secondary infection with an intra-phagosomal pathogen we employed Leishmania major-red fluorescent protein (RFP) parasites and multi-color flow cytometry to define and enumerate infected and uninfected inflammatory cells in the skin. During primary infection, infected monocytes had altered maturation and were the initial mononuclear host cell for parasite replication...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28655972/high-glucose-level-disturbs-the-resveratrol-evoked-curtailment-of-cx3cl1-cx3cr1-signaling-in-human-placental-circulation
#16
Dariusz Szukiewicz, Michal Pyzlak, Grzegorz Szewczyk, Aleksandra Stangret, Seweryn Trojanowski, Michal Bachanek, Wojciech Braksator, Jaroslaw Wejman
Hyperglycemia-induced hyperactivity of chemokine CX3CL1 (fractalkine) occurs in the human placenta. Anti-inflammatory/antioxidant activities of resveratrol (3,5,4'-trihydroxy-trans-stilbene) are related to the modulation of chemokine CX3CL1 and its receptor, CX3CR1, signaling pathways. We examined the influence of high glucose (25 mmol/L glucose; HG group; N = 36) on resveratrol-mediated effects on CX3CL1 and TNF-α production by the placental lobule, CX3CR1 expression and contents of CX3CR1, TNF-α receptor 1 (TNFR1), and NF-κB proteins in placental tissue...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28650582/synergistic-modulation-of-inflammatory-but-not-metabolic-effects-of-high-fat-feeding-by-ccr2-and-cx3cr1
#17
Hanrui Zhang, Christine C Hinkle, Sean M O'Neill, Jianting Shi, Jennifer Caughey, Emma Lynch, Gina Lynch, Mark Gerelus, Andrew S D Tsai, Rachana Shah, Jane F Ferguson, Rexford S Ahima, Muredach P Reilly
OBJECTIVE: The purpose of the study was to explore the impact of dual targeting of C-C motif chemokine receptor-2 (CCR2) and fractalkine receptor (CX3CR1) on the metabolic and inflammatory consequences of obesity induced by a high-fat diet (HFD). METHODS: C57BL/6J wild-type, Cx3cr1(-/-) , Ccr2(-/-) , and Cx3cr1(-/-) Ccr2(-/-) double-knockout male and female mice were fed a 45% HFD for up to 25 weeks starting at 12 weeks of age. RESULTS: All groups gained weight at a similar rate and developed a similar degree of adiposity, hyperglycemia, glucose intolerance, and impairment of insulin sensitivity in response to HFD...
June 26, 2017: Obesity
https://www.readbyqxmd.com/read/28650342/inflammatory-ly6chi-monocytes-and-their-conversion-to-m2-macrophages-drive-atherosclerosis-regression
#18
Karishma Rahman, Yuliya Vengrenyuk, Stephen A Ramsey, Noemi Rotllan Vila, Natasha M Girgis, Jianhua Liu, Viktoria Gusarova, Jesper Gromada, Ada Weinstock, Kathryn J Moore, P'ng Loke, Edward A Fisher
Atherosclerosis is a chronic inflammatory disease, and developing therapies to promote its regression is an important clinical goal. We previously established that atherosclerosis regression is characterized by an overall decrease in plaque macrophages and enrichment in markers of alternatively activated M2 macrophages. We have now investigated the origin and functional requirement for M2 macrophages in regression in normolipidemic mice that received transplants of atherosclerotic aortic segments. We compared plaque regression in WT normolipidemic recipients and those deficient in chemokine receptors necessary to recruit inflammatory Ly6Chi (Ccr2-/- or Cx3cr1-/-) or patrolling Ly6Clo (Ccr5-/-) monocytes...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28648458/peripheral-nerve-injury-induces-a-transitory-microglial-reaction-in-the-rat-infralimbic-cortex
#19
Paul Chu Sin Chung, Tania Panigada, Romain Cardis, Isabelle Decosterd, Romain-Daniel Gosselin
Undeniable evidence shows that microglia in the spinal cord undergo marked reactions following peripheral injuries. However, only rare studies have investigated the possible short and long term microglial reaction in brain regions following peripheral nerve injury and its interspecies specificities. In the present study we examined microglia in subdivisions of the prefrontal cortex in mice and rats, 7days and 42days after spared nerve injury (SNI) of the sciatic nerve. We show that a bilateral increase of microglial density takes place in the infralimbic cortex in rats 7days post-injury (sham vs...
June 23, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28646166/atp-release-during-cell-swelling-activates-a-ca-2-dependent-cl-current-by-autocrine-mechanism-in-mouse-hippocampal-microglia
#20
E Murana, F Pagani, B Basilico, M Sundukova, L Batti, S Di Angelantonio, B Cortese, A Grimaldi, A Francioso, P Heppenstall, P Bregestovski, C Limatola, D Ragozzino
Microglia cells, resident immune cells of the brain, survey brain parenchyma by dynamically extending and retracting their processes. Cl(-) channels, activated in the cellular response to stretch/swelling, take part in several functions deeply connected with microglia physiology, including cell shape changes, proliferation, differentiation and migration. However, the molecular identity and functional properties of these Cl(-) channels are largely unknown. We investigated the properties of swelling-activated currents in microglial from acute hippocampal slices of Cx3cr1 (+/GFP) mice by whole-cell patch-clamp and imaging techniques...
June 23, 2017: Scientific Reports
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