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Embryonic macrophage

Svenja Loering, Guy J M Cameron, Malcolm R Starkey, Philip M Hansbro
Lung development is a complex process mediated through the interaction of multiple cell types, factors and mediators. In mice, it starts as early as embryonic day 9 and continues into early adulthood. The process can be separated into five different developmental stages: embryonic, pseudoglandular, canalicular, saccular and alveolar. Whilst lung bud formation and branching morphogenesis have been studied extensively, the mechanisms of alveolarization are incompletely understood. Aberrant lung development can lead to deleterious consequences for respiratory health such as bronchopulmonary dysplasia, a disease primarily affecting preterm neonates, which is characterized by increased pulmonary inflammation and disturbed alveolarization...
December 2, 2018: Journal of Pathology
Ling Ling, Jingjing Wen, Liang Tao, Mengshu Zhao, Wenhao Ge, Lei Wang, Jianfa Zhang, Dan Weng
Tributyltin (TBT), a widely distributed environmental pollutant, is toxic to animals and human beings. Although its toxicity, especially the immunosuppressive effect, has been reported a lot, the underlying molecular mechanisms are still unclear. In this study, we investigated the mechanisms of TBT-induced cytotoxicity both in vitro and in vivo. TBT induced cell death in both J774A.1 macrophages and mouse bone marrow-derived macrophages (BMDMs) as measured by the LDH and Annexin V-FITC/PI dual staining assays...
November 24, 2018: Chemosphere
Atsuko Katsumoto, Hideyuki Takeuchi, Keita Takahashi, Fumiaki Tanaka
Microglia are resident immune cells in the central nervous system (CNS) that originate from myeloid progenitor cells in the embryonic yolk sac and are maintained independently of circulating monocytes throughout life. In the healthy state, microglia are highly dynamic and control the environment by rapidly extending and retracting their processes. When the CNS is inflamed, microglia can give rise to macrophages, but the regulatory mechanisms underlying this process have not been fully elucidated. Recent genetic studies have suggested that microglial function is compromised in Alzheimer's disease (AD), and that environmental factors such as diet and brain injury also affect microglial activation...
2018: Frontiers in Neurology
Andrea G Edlow, Ruthy M Glass, Caroline J Smith, Phuong Kim Tran, Kaitlyn James, Staci Bilbo
Fetal placental macrophages and microglia (resident brain macrophages) have a common origin in the fetal yolk sac. Yolk-sac-derived macrophages comprise the permanent pool of brain microglia throughout an individual's lifetime. Inappropriate fetal microglial priming may therefore have lifelong neurodevelopmental consequences, but direct evaluation of microglial function in a living fetus or neonate is impossible. We sought to test the hypothesis that maternal obesity would prime both placental macrophages and fetal brain microglia to overrespond to an immune challenge, thus providing a window into microglial function using placental cells...
November 20, 2018: International Journal of Developmental Neuroscience
Ayaka Nakanishi, Naoe Kaneko, Hiroyuki Takeda, Tatsuya Sawasaki, Shinnosuke Morikawa, Wei Zhou, Mie Kurata, Toshihiro Yamamoto, Sheikh Mohammad Fazle Akbar, Tamotsu Zako, Junya Masumoto
Background: Alzheimer's disease is a neurodegenerative disease characterized by the interstitial deposition of amyloid β (Aβ) plaque, which is thought to be related to chronic neuroinflammation. Aβ is known to make fibrils via oligomers from monomers. Aβ has been reported to activate the NLRP3 inflammasome in infiltrated macrophages. NLRP3, an intracellular pattern recognition receptor, has been reported to recognize numerous pathogens and/or metabolites and form complexes with adopter protein ASC to make the inflammasome, an interleukin (IL)-1β-processing platform...
2018: Inflammation and Regeneration
Harald Lund, Melanie Pieber, Roham Parsa, Jinming Han, David Grommisch, Ewoud Ewing, Lara Kular, Maria Needhamsen, Alexander Espinosa, Emma Nilsson, Anna K Överby, Oleg Butovsky, Maja Jagodic, Xing-Mei Zhang, Robert A Harris
Circulating monocytes can compete for virtually any tissue macrophage niche and become long-lived replacements that are phenotypically indistinguishable from their embryonic counterparts. As the factors regulating this process are incompletely understood, we studied niche competition in the brain by depleting microglia with >95% efficiency using Cx3cr1CreER/+ R26DTA/+ mice and monitored long-term repopulation. Here we show that the microglial niche is repopulated within weeks by a combination of local proliferation of CX3CR1+ F4/80low Clec12a- microglia and infiltration of CX3CR1+ F4/80hi Clec12a+ macrophages that arise directly from Ly6Chi monocytes...
November 19, 2018: Nature Communications
Deepti Vipin, Lingfei Wang, Guillaume Devailly, Tom Michoel, Anagha Joshi
Transcription control plays a crucial role in establishing a unique gene expression signature for each of the hundreds of mammalian cell types. Though gene expression data have been widely used to infer cellular regulatory networks, existing methods mainly infer correlations rather than causality. We developed statistical models and likelihood-ratio tests to infer causal gene regulatory networks using enhancer RNA (eRNA) expression information as a causal anchor and applied the framework to eRNA and transcript expression data from the FANTOM Consortium...
November 15, 2018: International Journal of Molecular Sciences
Upasama De Silva Senapathi, Mohamed Sarjoon Abdul-Cader, Aruna Amarasinghe, Guido van Marle, Markus Czub, Susantha Gomis, Mohamed Faizal Abdul-Careem
The in ovo delivery of cytosine-guanosine (CpG) oligodeoxynucleotides (ODNs) protects chickens against many bacterial and viral infections, by activating the toll-like receptor (TLR)21 signaling pathway. Although the delivery of CpG ODNs in ovo at embryo day (ED) 18 has been shown to reduce infectious bronchitis virus (IBV) loads in embryonic chicken lungs pre-hatch, whether in ovo delivered CpG ODNs are capable of protecting chickens against a post-hatch challenge is unknown. Thus, our objectives were to determine the protective effect of the in ovo delivery of CpG ODNs at ED 18 against IBV infection encountered post-hatch and, then, to investigate the mechanisms of protection...
November 15, 2018: Viruses
Denver D Britto, Barbara Wyroba, Wenxuan Chen, Rhoswen A Lockwood, Khanh B Tran, Peter R Shepherd, Christopher J Hall, Kathryn E Crosier, Philip S Crosier, Jonathan W Astin
Tumour angiogenesis has long been a focus of anti-cancer therapy; however, anti-angiogenic cancer treatment strategies have had limited clinical success. Tumour-associated myeloid cells are believed to play a role in the resistance of cancer towards anti-angiogenesis therapy, but the mechanisms by which they do this are unclear. An embryonic zebrafish xenograft model has been developed to investigate the mechanisms of tumour angiogenesis and as an assay to screen anti-angiogenic compounds. In this study, we used cell ablation techniques to remove either macrophages or neutrophils and assessed their contribution towards zebrafish xenograft angiogenesis by quantitating levels of graft vascularisation...
November 29, 2018: Disease Models & Mechanisms
Brian C Wulff, Nicholas K Pappa, Traci A Wilgus
The magnitude of the inflammatory response after skin injury is important for determining whether wounds in developing fetal skin will heal scarlessly (minimal inflammation) or with prominent scars (robust inflammation). One class of inflammatory mediators gaining attention for their role in wound inflammation is alarmins. In the current study, the alarmin IL-33 was examined in a mouse model of fetal wound healing. IL-33 expression was elevated in scar-forming embryonic day 18 wounds compared to scarless embryonic day 15 wounds...
October 28, 2018: Wound Repair and Regeneration
William D'Angelo, Bohan Chen, Chandan Gurung, Yan-Lin Guo
BACKGROUND: Mesenchymal stem cells (MSCs) isolated from adult tissues (Ad-MSCs) have shown great promise for use in regenerative medicine. However, their poor in vitro expansion capacity and tissue scarcity have been major limitations. In this study, we demonstrate that mouse embryonic stem cells (mESCs) can differentiate into cells with MSC properties. METHODS: Using previously established methods that characterize Ad-MSCs, we analyzed mESC-differentiated fibroblasts (mESC-FBs), including plastic adherence, clonogenic growth, MSC marker expression, tri-lineage differentiation potential, and the capacity to express immunomodulators...
October 25, 2018: Stem Cell Research & Therapy
Sambit K Nanda, Tsunehisa Nagamori, Mark Windheim, Sylvia Amu, Gabriella Aviello, Janet Patterson-Kane, J Simon C Arthur, Steven C Ley, Padraic Fallon, Philip Cohen
The A20-binding inhibitor of NF-κB 2 (ABIN2) interacts with Met1-linked ubiquitin chains and is an integral component of the tumor progression locus 2 (Tpl2) kinase complex. We generated a knock-in mouse expressing the ubiquitin-binding-defective mutant ABIN2[D310N]. The expression of Tpl2 and its activation by TLR agonists in macrophages or by IL-1β in fibroblasts from these mice was unimpaired, indicating that the interaction of ABIN2 with ubiquitin oligomers is not required for the stability or activation of Tpl2...
October 24, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Anne-Sophie Cabron, Karim El Azzouzi, Melanie Boss, Philipp Arnold, Jeanette Schwarz, Marcela Rosas, Jan Philipp Dobert, Egor Pavlenko, Neele Schumacher, Thomas Renné, Philip R Taylor, Stefan Linder, Stefan Rose-John, Friederike Zunke
A disintegrin and metalloproteinase (ADAM) 17 has been implicated in many shedding processes. Major substrates of ADAM17 are TNF-α, IL-6R, and ligands of the epidermal growth factor receptor. The essential role of the protease is emphasized by the fact that ADAM17 deficiency is lethal in mice. To study ADAM17 function in vivo, we generated viable hypomorphic ADAM17 mice called ADAM17ex/ex mice. Recent studies indicated regulation of proteolytic ADAM17 activity by cellular processes such as cytoplasmic phosphorylation and removal of the prodomain by furin cleavage...
November 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Subba Rao Mekala, Philipp Wörsdörfer, Jochen Bauer, Olga Stoll, Nicole Wagner, Laurens Reeh, Kornelia Loew, Georg Eckner, Chee Keong Kwok, Erhard Wischmeyer, Mary Eleanor Dickinson, Harald Schulze, David Stegner, Ralf A Benndorf, Frank Edenhofer, Verena Pfeiffer, Stefanie Kuerten, Stefan Frantz, Süleyman Ergün
RATIONALE: Regeneration of lost cardiomyocytes is a fundamental unresolved problem leading to heart failure. Despite several strategies developed from intensive studies performed in the past decades, endogenous regeneration of heart tissue is still limited and presents a big challenge that needs to be overcome to serve as a successful therapeutic option for myocardial infarction. OBJECTIVE: One of the essential prerequisites for cardiac regeneration is the identification of endogenous cardiomyocyte progenitors and their niche that can be targeted by new therapeutic approaches...
August 31, 2018: Circulation Research
Masateru Kondo, Masaki Imanishi, Keijo Fukushima, Raiki Ikuto, Yoichi Murai, Yuya Horinouchi, Yuki Izawa-Ishizawa, Mitsuhiro Goda, Yoshito Zamami, Kenshi Takechi, Masayuki Chuma, Yasumasa Ikeda, Hiromichi Fujino, Koichiro Tsuchiya, Keisuke Ishizawa
BACKGROUND: Several reports from basic researches and clinical studies have suggested that xanthine oxidase (XO) inhibitors have suppressive effects on cardiovascular diseases. However, the roles of a XO inhibitor, febuxostat (FEB), in the pathogenesis of vascular remodelling and hypertension independent of the serum uric acid level remain unclear. METHODS: To induce vascular remodelling in mice, angiotensin II (Ang II) was infused for 2 weeks with a subcutaneously implanted osmotic minipump...
October 23, 2018: American Journal of Hypertension
Sanjiv Kumar, Jagbir Singh, Balasubramanian Narasimhan, Syed Adnan Ali Shah, Siong Meng Lim, Kalavathy Ramasamy, Vasudevan Mani
BACKGROUND: Pyrimidine is an important pharmacophore in the field of medicinal chemistry and exhibit a broad spectrum of biological potentials. A study was carried out to identify the target protein of potent bis-pyrimidine derivatives using reverse docking program. PharmMapper, a robust online tool was used for identifying the target proteins based on reverse pharmacophore mapping. The murine macrophage (RAW 264.7) and human embryonic kidney (HEK-293) cancer cell line used for selectivity and safety study...
October 22, 2018: Chemistry Central Journal
Luca Giordano, Antoine Farnham, Praveen K Dhandapani, Laura Salminen, Jahnavi Bhaskaran, Robert Voswinckel, Peter Rauschkolb, Susan Scheibe, Natascha Sommer, Christoph Beisswenger, Norbert Weissmann, Thomas Braun, Howard T Jacobs, Robert Bals, Christian Herr, Marten Szibor
Cigarette-smoke (CS) exposure is the predominant risk factor for the development of chronic obstructive pulmonary disease (COPD) and the third leading cause of death worldwide. We aimed to elucidate if mitochondrial respiratory inhibition and oxidative stress are triggers in its etiology. In different models of CS exposure, we investigated the effect on lung remodeling and cell signaling of restoring mitochondrial respiratory electron flow, using the alternative oxidase (AOX), which by-passes the cytochrome segment of the respiratory chain...
October 19, 2018: American Journal of Respiratory Cell and Molecular Biology
Nancy J Reyes, Rose Mathew, Daniel R Saban
With the new understanding that adult microglia in mice have embryonic origins and are maintained in situ throughout life, it has become pertinent to now understand how these unique cells differ from monocyte-derived macrophages. The latter are recruited into the neural retina (and elsewhere in CNS) in certain diseased states, such as in various forms of retinal degeneration. However, phenotypic markers expressed by microglia and monocyte-derived macrophages largely overlap, thereby making it technically challenging to distinguish the two cell types in disease...
2019: Methods in Molecular Biology
Yilang Tang, Sonja Reissig, Elke Glasmacher, Tommy Regen, Florian Wanke, Alexei Nikolaev, Katharina Gerlach, Vanessa Popp, Khalad Karram, Massimo C Fantini, Jörn M Schattenberg, Peter R Galle, Markus F Neurath, Benno Weigmann, Florian C Kurschus, Nadine Hövelmeyer, Ari Waisman
BACKGROUND & AIMS: The CYLD lysine 63 deubiquitinase gene (CYLD) encodes tumor suppressor protein that is mutated in familial cylindromatosis, and variants have been associated with Crohn's disease (CD). Splice forms of CYLD that lack exons 7 and 8 regulate transcription factors and functions of immune cells. We examined expression of splice forms of CYLD in colon tissues from patients with CD and their effects in mice. METHODS: We performed immunohistochemical analyses of colon tissues from untreated patients with CD and patients without inflammatory bowel diseases (controls)...
October 10, 2018: Gastroenterology
Kate Sutton, Taiana Costa, Andreas Alber, Karen Bryson, Dominika Borowska, Adam Balic, Pete Kaiser, Mark Stevens, Lonneke Vervelde
The respiratory tract is a key organ for many avian pathogens as well as a major route for vaccination in the poultry industry. To improve immune responses after vaccination of chickens through increased uptake of vaccines and targeting to antigen presenting cells, a better understanding of the avian respiratory immune system is required. Transgenic MacReporter birds were used expressing a reporter gene (eGFP or mApple) under the control of the CSF1R promoter and enhancer in cells of the mononuclear phagocyte (MNP) lineage to visualize the ontogeny of the lymphoid tissue, macrophages and dendritic cells, in the trachea, lung and air sac of birds from embryonic day 18-63 weeks of age...
October 10, 2018: Veterinary Research
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