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https://www.readbyqxmd.com/read/29341339/immunomodulation-by-therapeutic-mesenchymal-stromal-cells-msc-is-triggered-through-phagocytosis-of-msc-by-monocytic-cells
#1
Samantha F H de Witte, Franka Luk, Jesus M Sierra Parraga, Madhu Gargesha, Ana Merino, Sander S Korevaar, Anusha S Shankar, Lisa O'Flynn, Steve J Elliman, Debashish Roy, Michiel G H Betjes, Philip N Newsome, Carla C Baan, Martin J Hoogduijn
Mesenchymal stem or stromal cells (MSC) are under investigation as a potential immunotherapy. MSC are usually administered via intravenous infusion, after which they are trapped in the lungs and die and disappear within a day. The fate of MSC after their disappearance from the lungs is unknown and it is unclear how MSC realize their immunomodulatory effects in their short lifespan. We examined immunological mechanisms determining the fate of infused MSC and the immunomodulatory response associated with it. Tracking viable and dead human umbilical cord MSC (ucMSC) in mice using Qtracker beads (contained in viable cells) and Hoechst33342 (staining all cells) revealed that viable ucMSC were present in the lungs immediately after infusion...
January 17, 2018: Stem Cells
https://www.readbyqxmd.com/read/29341332/cornea-derived-mscs-therapeutically-modulate-macrophage-immunophenotype-and-angiogenic-function
#2
Medi Eslani, Ilham Putra, Xiang Shen, Judy Hamouie, Asha Tadepalli, Khandaker N Anwar, John A Kink, Samaneh Ghassemi, Gaurav Agnihotri, Sofiya Reshetylo, Alireza Mashaghi, Reza Dana, Peiman Hematti, Ali R Djalilian
Macrophages are crucial drivers of inflammatory corneal neovascularization and thus are potential targets for immunomodulatory therapies. We hypothesized that therapeutic use of cornea derived mesenchymal stromal cells (cMSCs) may alter the function of macrophages. We found that cMSCs can modulate the phenotype and angiogenic function of macrophages. In vitro, cMSCs induce apoptosis of macrophages while preferentially promoting a distinct CD14hi CD16hi CD163hi CD206hi immunophenotype that has significantly reduced angiogenic effects based on in vitro angiogenesis assays...
January 17, 2018: Stem Cells
https://www.readbyqxmd.com/read/29332538/role-of-infiltrating-monocytes-in-the-development-of-radiation-induced-pulmonary-fibrosis
#3
Angela M Groves, Carl J Johnston, Jacqueline P Williams, Jacob N Finkelstein
Lung exposure to radiation induces an injury response that includes the release of cytokines and chemotactic mediators; these signals recruit immune cells to execute inflammatory and wound-healing processes. However, radiation alters the pulmonary microenvironment, dysregulating the immune responses and preventing a return to homeostasis. Importantly, dysregulation is observed as a chronic inflammation, which can progress into pneumonitis and promote pulmonary fibrosis; inflammatory monocytes, which are bone marrow derived and express CCR2, have been shown to migrate into the lung after radiation exposure...
January 13, 2018: Radiation Research
https://www.readbyqxmd.com/read/29329953/canine-macrophages-can-like-human-macrophages-be-in-vitro-activated-toward-the-m2a-subtype-relevant-in-allergy
#4
Ina Herrmann, Jelena Gotovina, Judit Fazekas-Singer, Michael B Fischer, Karin Hufnagl, Rodolfo Bianchini, Erika Jensen-Jarolim
The M2a subtype of macrophages plays an important role in human immunoglobulin E (IgE-mediated allergies) and other Th2 type immune reactions. In contrast, very little is known about these cells in the dog. Here we describe an in-vitro method to activate canine histiocytic DH82 cells and primary canine monocyte-derived macrophages (MDMs) toward the M2a macrophages using human cytokines. For a side-by-side comparison, we compared the canine cells to human MDMs, and the human monocytic cell line U937 activated towards M1-and M2a cells on the cellular and molecular level...
January 9, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29321062/notch-signaling-triggered-via-the-ligand-dll4-impedes-m2-macrophage-differentiation-and-promotes-their-apoptosis
#5
Sylvain Pagie, Nathalie Gérard, Béatrice Charreau
BACKGROUND: Notch signaling controls many cellular processes, including cell fate determination, cell differentiation, proliferation and apoptosis. In mammals, four Notch receptors (Notch 1-4) can interact with five distinct ligands [Jagged1, Jagged2, Delta-like 1 (DLL1), DLL3, and DLL4]. We previously reported that Notch activation is modulated in endothelial cells and monocytes during inflammation and showed that inflammation upregulates DLL4 on endothelial cells. DLL4 promotes differentiation of blood monocytes into proinflammatory M1 macrophages...
January 10, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29310519/intranasal-stem-cell-treatment-as-a-novel-therapy-for-subarachnoid-hemorrhage
#6
Cora H Nijboer, Elke Kooijman, Cindy T van Velthoven, Erik Van Tilborg, Ivo A Tiebosch, Niels Eijkelkamp, Rick M Dijkhuizen, Jozef Kesecioglu, Cobi Heijnen
Subarachnoid hemorrhage (SAH) represents a major health problem in Western society due to high mortality and morbidity, and the relative young age of patients. Currently, efficacious therapeutic options are very limited. Mesenchymal stem cell (MSC) administration has been shown to improve functional outcome and lesion size in experimental models of stroke and neonatal hypoxic-ischemic brain injury. Here we studied the therapeutic potential of intranasally administered bone marrow-derived MSCs relatively late post-insult using a rat endovascular puncture model for SAH...
January 8, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29304229/cd16-macrophages-mediate-fibrosis-in-inflammatory-bowel-disease
#7
Pedro Salvador, Dulce Carolina Macías-Ceja, Laura Gisbert-Ferrándiz, Carlos Hernández, David Bernardo, Rafael Alós, Francisco Navarro-Vicente, Juan Vicente Esplugues, Dolores Ortiz-Masiá, Maria Dolores Barrachina, Sara Calatayud
Background and aims: Fibrosis is a common complication of Crohn's disease, and is related with dysregulated tissular repair following inflammation, in which macrophages play a central role. We have previously observed that STAT6-/- mice present delayed mucosal recovery after TNBS-induced colitis due to a deficiency in reparatory IL4/STAT6-dependent M2 macrophages, which can be reverted by the exogenous transfer of this cell type. In the present study we aimed to analyze the role of STAT6-dependent macrophages in intestinal fibrosis...
January 3, 2018: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29296945/the-class-i-scavenger-receptor-cd163-promotes-internalization-of-adamts13-by-macrophages
#8
Fabian C Verbij, Nicoletta Sorvillo, Paul H P Kaijen, Johana Hrdinova, Ivan Peyron, Rob Fijnheer, Anja Ten Brinke, Alexander B Meijer, Floris P J van Alphen, Timo K van den Berg, Jonas J H Graversen, Soren K Moestrup, Jan Voorberg
Internalization of ADAMTS13 by macrophages may contribute to its clearance from the circulation. Here we investigated endocytic mechanisms that contribute to the uptake of ADAMTS13 by macrophages. Human monocyte-derived macrophages were used to monitor the uptake of fluorescently labeled recombinant ADAMTS13 by flow cytometry. Internalization of ADAMTS13 was blocked upon addition of the cell-permeable dynamin inhibitor dynasore. Partial blocking of ADAMTS13 uptake was observed by using mannan; however, uptake was not affected by an antibody that blocked binding to the macrophage mannose receptor CD206, which suggests that other endocytic receptors contribute to the internalization of ADAMTS13 by macrophages...
January 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295986/macrophages-orchestrate-breast-cancer-early-dissemination-and-metastasis
#9
Nina Linde, Maria Casanova-Acebes, Maria Soledad Sosa, Arthur Mortha, Adeeb Rahman, Eduardo Farias, Kathryn Harper, Ethan Tardio, Ivan Reyes Torres, Joan Jones, John Condeelis, Miriam Merad, Julio A Aguirre-Ghiso
Cancer cell dissemination during very early stages of breast cancer proceeds through poorly understood mechanisms. Here we show, in a mouse model of HER2+ breast cancer, that a previously described sub-population of early-evolved cancer cells requires macrophages for early dissemination. Depletion of macrophages specifically during pre-malignant stages reduces early dissemination and also results in reduced metastatic burden at end stages of cancer progression. Mechanistically, we show that, in pre-malignant lesions, CCL2 produced by cancer cells and myeloid cells attracts CD206+/Tie2+ macrophages and induces Wnt-1 upregulation that in turn downregulates E-cadherin junctions in the HER2+ early cancer cells...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29290023/immunological-hallmarks-of-cis-ddp-resistant-lewis-lung-carcinoma-cells
#10
Olexandr Fedorchuk, Yaroslav Susak, Mariia Rudyk, Nataliia Senchylo, Nataliia Khranovska, Oksana Skachkova, Larysa Skivka
PURPOSE: Tumor cell resistance to platinum-based chemotherapeutic agents is one of the major hurdles to successful cancer treatment with these drugs, and is associated with alterations in tumor cell immune evasion and immunomodulatory properties. Immunocyte targeting is considered as a relevant approach to fight drug-resistant cancer. In this study, immunological hallmarks of cis-DDP-resistant Lewis lung carcinoma cells (LLC/R9) were investigated. METHODS: Immunological features of LLC/R9 cells cultured in vitro in normoxic and hypoxic conditions as well as of those that were grown in vivo were examined...
December 30, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29285874/early-cellular-interactions-and-immune-transcriptome-profiles-in-human-factor-viii-exposed-hemophilia-a-mice
#11
J D Lai, D Cartier, R B Hartholt, L L Swystun, A S van Velzen, J M M den Haan, C Hough, J Voorberg, D Lillicrap
BACKGROUND: Developing factor VIII (FVIII) inhibitory antibodies is the most serious complication in hemophilia A treatment, representing a significant health and economic burden. A better understanding of the early events in an immune response leading to this outcome may provide insight into inhibitor development. OBJECTIVE: To identify early mediators of FVIII immunity and to detail immune expression profiles in the spleen and liver. METHODS: C57Bl/6 F8 E16 knockout mice were infused with 5-20 μg (2000-8000 IU/kg) of recombinant FVIII...
December 28, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29284682/glucocorticoids-induce-differentiation-of-monocytes-towards-macrophages-that-share-functional-and-phenotypical-aspects-with-erythroblastic-island-macrophages
#12
Esther Heideveld, Lea A Hampton-O'Neil, Stephen J Cross, Floris P J van Alphen, Maartje van den Biggelaar, Ashley M Toye, Emile van den Akker
The classical central macrophage found in erythroblastic islands plays an important role in erythroblast differentiation, proliferation and enucleation in the bone marrow. Convenient human in vitro models to facilitate the study of erythroid-macrophage interactions are desired. Recently, we demonstrated that cultured monocytes/macrophages enhance in vitro erythropoiesis by supporting hematopoietic stem cell survival. Here, we describe that these specific macrophages also support erythropoiesis. Human monocytes cultured in serum-free media supplemented with stem cell factor, erythropoietin, lipids and dexamethasone differentiate towards macrophages expressing CD16, CD163, CD169, CD206, CXCR4 and the phagocytic TAM-receptor family...
December 28, 2017: Haematologica
https://www.readbyqxmd.com/read/29283442/myeloid-cell-plasticity-in-the-evolution-of-central-nervous-system-autoimmunity
#13
David A Giles, Jesse M Washnock-Schmid, Patrick C Duncker, Somiah Dahlawi, Gerald Ponath, David Pitt, Benjamin M Segal
OBJECTIVE: Myeloid cells, including macrophages and dendritic cells, are a prominent component of central nervous system (CNS) infiltrates during multiple sclerosis (MS) and the animal model experimental autoimmune encephalomyelitis (EAE). Although myeloid cells are generally thought to be pro-inflammatory, alternatively-polarized subsets can serve non-inflammatory and/or reparative functions. Here we investigate the heterogeneity and biological properties of myeloid cells during central nervous system autoimmunity...
December 28, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/29251792/extracellular-vesicles-from-mice-with-alcoholic-liver-disease-carry-a-distinct-protein-cargo-and-induce-macrophage-activation-via-hsp90
#14
Banishree Saha, Fatemeh Momen-Heravi, Istvan Furi, Karen Kodys, Donna Catalano, Anwesha Gangopadhyay, Reka Haraszti, Abhishek Satishchandran, Arvin Iracheta-Vellve, Adeyinka Adejumo, Scott A Shaffer, Gyongyi Szabo
A salient feature of alcoholic liver disease (ALD) is Kupffer cell (KC) activation and recruitment of inflammatory monocytes/macrophages (Mo/MØ). These key cellular events of ALD pathogenesis may be mediated by extracellular vesicles (EVs). EVs transfer biomaterials, including proteins and miRNAs, and have recently emerged as important effectors of intercellular communication. We hypothesized that circulating EVs from mice with ALD have a protein cargo characteristic of the disease and mediate biological effects by activating immune cells...
December 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29250069/histamine-regulates-the-inflammatory-profile-of-sod1-g93a-microglia-and-the-histaminergic-system-is-dysregulated-in-amyotrophic-lateral-sclerosis
#15
Savina Apolloni, Paola Fabbrizio, Susanna Amadio, Giulia Napoli, Veronica Verdile, Giovanna Morello, Rosario Iemmolo, Eleonora Aronica, Sebastiano Cavallaro, Cinzia Volonté
Amyotrophic lateral sclerosis (ALS) is a late-onset motor neuron disease where activated glia release pro-inflammatory cytokines that trigger a vicious cycle of neurodegeneration in the absence of resolution of inflammation. Given the well-established role of histamine as a neuron-to-glia alarm signal implicated in brain disorders, the aim of this study was to investigate the expression and regulation of the histaminergic pathway in microglial activation in ALS mouse model and in humans. By examining the contribution of the histaminergic system to ALS, we found that particularly via H1 and H4 receptors, histamine promoted an anti-inflammatory profile in microglia from SOD1-G93A mice by modulating their activation state...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29249750/progranulin-deficiency-leads-to-prolonged-persistence-of-macrophages-accompanied-with-myofiber-hypertrophy-in-regenerating-muscle
#16
Hidetoshi Sugihara, Kei Miyaji, Keitaro Yamanouchi, Takashi Matsuwaki, Masugi Nishihara
Skeletal muscle has an ability to regenerate in response to injury due to the presence of satellite cells. Injury in skeletal muscle causes infiltration of pro-inflammatory macrophages (M1 macrophages) to remove necrotic myofibers, followed by their differentiation into anti-inflammatory macrophages (M2 macrophages) to terminate the inflammation. Since both M1 and M2 macrophages play important roles, coordinated regulation of their kinetics is important to complete muscle regeneration successfully. Progranulin (PGRN) is a pluripotent growth factor, having a protective role against the inflamed tissue...
December 18, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29249556/both-classic-gs-camp-pka-creb-and-alternative-gs-camp-pka-p38%C3%AE-creb-signal-pathways-mediate-exenatide-stimulated-expression-of-m2-microglial-markers
#17
Hai-Yun Wu, Xue-Qi Tang, Hao Liu, Xiao-Fang Mao, Yong-Xiang Wang
GLP-1 receptor agonists, exenatide and GLP-1, promoted M2 type polarization in monocytes/macrophages and microglial cells. This study explored the signal basis underlying exenatide-stimulated expression of M2 microglia-specific genes, including the cytoplasmic marker Arg 1, surface marker CD206, and secretion protein marker IL-4. Treatment with exenatide in cultured primary microglial cells concentration dependently stimulated the expression of Arg 1, CD206 and IL-4, but did not significantly alter LPS-stimulated expression of TNF-α, IL-1β and IL-6...
December 12, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29248792/crocin-alleviates-coronary-atherosclerosis-via-inhibiting-lipid-synthesis-and-inducing-m2-macrophage-polarization
#18
Jing Li, Hong-Tao Lei, Lei Cao, Yan-Ni Mi, Sen Li, Yong-Xiao Cao
Atherosclerosis is a chronic inflammatory disease arising from an imbalance in lipid levels and the accumulation of cholesterol-laden macrophages in the artery wall. Crocin is an active ingredient of Crocus sativus L. This study established a rat coronary atherosclerosis model induced by vitamin D3 (VD3), to explore the effect of Crocin on lipid metabolism, macrophage polarization and the activity of inflammatory proteins. The results revealed that Crocin decreased blood lipid levels by decreasing the levels of endothelin (ET), total cholesterol (TC), triglyceridelow (TG) and low-density lipoprotein cholesterol (LDL-c), elevating the level of high-density lipoprotein cholesterin (HDL-c)...
December 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29248573/bisphenol-a-exposure-induces-increased-microglia-and-microglial-related-factors-in-the-murine-embryonic-dorsal-telencephalon-and-hypothalamus
#19
Mifumi Takahashi, Munekazu Komada, Ken Miyazawa, Shigemi Goto, Yayoi Ikeda
Bisphenol A (BPA) is a widely used compound in the food packaging industry. Prenatal exposure to BPA induces histological abnormalities in the neocortex and hypothalamus in association with abnormal behaviors. Yet, the molecular and cellular neurodevelopmental toxicological mechanisms of BPA are incompletely characterized on neuroinflammatory-related endopoints. To evaluate the neurodevelopmental effects of BPA exposure in mouse embryos, we examined microglial numbers as well as the expression of microglial-related factors in the E15...
December 14, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29245934/apolipoprotein-a-i-mimetic-peptide-4f-suppresses-tumor-associated-macrophages-and-pancreatic-cancer-progression
#20
Meiyu Peng, Qi Zhang, Yingnan Cheng, Shuyu Fu, Huipeng Yang, Xiangdong Guo, Jieyou Zhang, Lina Wang, Lijuan Zhang, Zhenyi Xue, Yan Li, Yurong Da, Zhi Yao, Liang Qiao, Rongxin Zhang
Pancreatic cancer is an aggressive malignancy that is unresponsive to conventional radiation and chemotherapy. Therefore, development of novel immune therapeutic strategies is urgently needed. L-4F, an Apolipoprotein A-I (ApoA-I) mimetic peptide, is engineered to mimic the anti-inflammatory and anti-oxidative functionalities of ApoA-I. In this work, H7 cells were orthotopically implanted in C57BL/6 mice and treated with L-4F. Then, pancreatic cancer progression and the inflammatory microenvironment were investigated in vivo...
November 21, 2017: Oncotarget
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