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Mubing Duan, Margaret L Hibbs, Weisan Chen
The lung myeloid cell microenvironment comprises airway, alveolar and interstitial macrophages, peripheral blood recruited lung monocytes as well as residential and migratory dendritic cell subsets. Findings from fate mapping, parabiosis, transcriptome and epigenome profiling studies now indicate that tissue macrophage and monocyte subsets possess specialized functions which differentially impact homoeostatic tolerance, pathogen detection and pathogen killing. In the lungs, residential alveolar macrophages are catabolic and immunosuppressive in contrast to the classically pro-inflammatory repertoire of lung monocytes and monocyte-derived dendritic cells recruited during acute inflammation...
October 18, 2016: Immunology and Cell Biology
Long Wang, Liang Xie, Francis Tintani, Hui Xie, Changjun Li, Zhuang Cui, Mei Wan, Xiongbing Zu, Lin Qi, Xu Cao
: : Benign prostatic hyperplasia (BPH) is the overgrowth of prostate tissues with high prevalence in older men. BPH pathogenesis is not completely understood, but it is believed to be a result of de novo overgrowth of prostatic stroma. In this study, we show that aberrant activation of transforming growth factor-β (TGF-β) mobilizes mesenchymal/stromal stem cells (MSCs) in circulating blood, which are recruited for the prostatic stromal hyperplasia. Elevated levels of active TGF-β were observed in both a phenylephrine-induced prostatic hyperplasia mouse model and human BPH tissues...
September 7, 2016: Stem Cells Translational Medicine
Jinte Middeldorp, Benoit Lehallier, Saul A Villeda, Suzanne S M Miedema, Emily Evans, Eva Czirr, Hui Zhang, Jian Luo, Trisha Stan, Kira I Mosher, Eliezer Masliah, Tony Wyss-Coray
Importance: Alzheimer disease (AD) pathology starts long before clinical symptoms manifest, and there is no therapy to treat, delay, or prevent the disease. A shared blood circulation between 2 mice (aka parabiosis) or repeated injections of young blood plasma (plasma from 2- to 3-month-old mice) into old mice has revealed benefits of young plasma on synaptic function and behavior. However, to our knowledge, the potential benefit of young blood has not been tested in preclinical models of neurodegeneration or AD...
September 6, 2016: JAMA Neurology
Xiao-Yi Xiong, Liang Liu, Fa-Xiang Wang, Yuan-Rui Yang, Jun-Wei Hao, Peng-Fei Wang, Qi Zhong, Kai Zhou, Ao Xiong, Wen-Yao Zhu, Ting Zhao, Zhao-You Meng, Yan-Chun Wang, Qiu-Wen Gong, Mao-Fan Liao, Jian Wang, Qing-Wu Yang
BACKGROUND: Disturbance of brain iron metabolism after intracerebral hemorrhage (ICH) results in oxidative brain injury and cognition impairment. Hepcidin plays an important role in regulating iron metabolism, and we have reported that serum hepcidin is positively correlated with poor outcomes in patients with ICH. However, the roles of hepcidin in brain iron metabolism after ICH remain largely unknown. METHODS: Parabiosis and ICH models combined with in vivo and in vitro experiments were used to investigate the roles of hepcidin in brain iron metabolism after ICH...
October 4, 2016: Circulation
Lige Song, Garyfallia Papaioannou, Hengguang Zhao, Hilary F Luderer, Christine Miller, Claudia Dall'Osso, Rosalynn M Nazarian, Amy J Wagers, Marie B Demay
Ligand-dependent actions of the vitamin D receptor (VDR) play a pleiotropic role in the regulation of innate and adaptive immunity. The liganded VDR is required for recruitment of macrophages during the inflammatory phase of cutaneous wound healing. Although the number of macrophages in the granulation tissue 2 days after wounding is markedly reduced in VDR knockout (KO) compared with wild-type mice, VDR ablation does not alter macrophage polarization. Parabiosis studies demonstrate that circulatory chimerism with wild-type mice is unable to rescue the macrophage defect in the wounds of VDR KO mice and reveal that wound macrophages are of local origin, regardless of VDR status...
October 2016: Endocrinology
Stefano Schiaffino, Marcelo G Pereira, Stefano Ciciliot, Patrizia Rovere-Querini
Skeletal muscle regeneration results from the activation and differentiation of myogenic stem cells, called satellite cells, located beneath the basal lamina of the muscle fibers. Inflammatory and immune cells have a crucial role in the regeneration process. Acute muscle injury causes an immediate transient wave of neutrophils followed by a more persistent infiltration of M1 (pro-inflammatory) and M2 (anti-inflammatory/pro-regenerative) macrophages. New studies show that injured muscle is also infiltrated by a specialized population of regulatory T (Treg) cells, which control both the inflammatory response, by promoting the M1-to-M2 switch, and the activation of satellite cells...
August 1, 2016: FEBS Journal
Jami Scheib, Ahmet Höke
Although many observational studies have shown that peripheral nerve regeneration is impaired with aging, underlying cellular and molecular mechanisms have remained obscure until recently. A series of recent genetic, live imaging and heterochronic parabiosis experiments are providing new insights into the underlying mechanisms of reduced regenerative capacity with aging. These studies show that Schwann cells in the aged animal pose a primary impediment to axon regeneration in older animals as they fail to support regenerating axons, while the contribution from macrophages remains an unresolved issue...
July 20, 2016: Experimental Neurology
Ruth A Franklin, Ming O Li
Tumors develop in a complex microenvironment alongside numerous cell types that impact their survival. Immune cells make up a large proportion of these accessory cells and many are known to promote tumor progression. Macrophages, in particular, are associated with poor patient prognosis and are therefore potential candidates for therapeutic targeting in cancer. However, to develop successful strategies to target macrophages, it is important to clarify whether these cells are derived from blood-borne precursors or a tissue-resident population...
August 20, 2015: Bio-protocol
Joseph M Castellano, Mikael Palner, Shi-Bin Li, G Mark Freeman, Andy Nguyen, Bin Shen, Trisha Stan, Kira I Mosher, Frederick T Chin, Luis de Lecea, Jian Luo, Tony Wyss-Coray
The sharing of circulation between two animals using a surgical procedure known as parabiosis has created a wealth of information towards our understanding of physiology, most recently in the neuroscience arena. The systemic milieu is a complex reservoir of tissues, immune cells, and circulating molecules that is surprisingly not well understood in terms of its communication across organ systems. While the model has been used to probe complex physiological questions for many years, critical parameters of recovery and exchange kinetics remain incompletely characterized, limiting the ability to design experiments and interpret results for complex questions...
2016: Scientific Reports
Elliott J Hagedorn, Jennifer L Cillis, Caitlyn R Curley, Taylor C Patch, Brian Li, Bradley W Blaser, Raquel Riquelme, Leonard I Zon, Dhvanit I Shah
Surgical parabiosis of two animals of different genetic backgrounds creates a unique scenario to study cell-intrinsic versus cell-extrinsic roles for candidate genes of interest, migratory behaviors of cells, and secreted signals in distinct genetic settings. Because parabiotic animals share a common circulation, any blood or blood-borne factor from one animal will be exchanged with its partner and vice versa. Thus, cells and molecular factors derived from one genetic background can be studied in the context of a second genetic background...
2016: Journal of Visualized Experiments: JoVE
Sho-Ichi Yamagishi, Takanori Matsui, Yuka Kurokawa, Kei Fukami
Circulating levels of growth differentiation factor 11 (GDF11) have been shown to decrease with age in several mammalian species, and supplementation of GDF11 by heterochronic parabiosis or systemic administration reverses age-related organ damage. However, there is some controversy about the pathophysiological role of GDF11 in aging-associated organ damage. Since aging process is accelerated in uremia, we compared serum levels of GDF11 in hemodialysis (HD) patients with those in age-matched healthy controls, and then determined the independent clinical correlates of GDF11 in HD subjects...
2016: BioResearch Open Access
Tobias Goldmann, Peter Wieghofer, Marta Joana Costa Jordão, Fabiola Prutek, Nora Hagemeyer, Kathrin Frenzel, Lukas Amann, Ori Staszewski, Katrin Kierdorf, Martin Krueger, Giuseppe Locatelli, Hannah Hochgerner, Robert Zeiser, Slava Epelman, Frederic Geissmann, Josef Priller, Fabio M V Rossi, Ingo Bechmann, Martin Kerschensteiner, Sten Linnarsson, Steffen Jung, Marco Prinz
Perivascular, subdural meningeal and choroid plexus macrophages are non-parenchymal macrophages that mediate immune responses at brain boundaries. Although the origin of parenchymal microglia has recently been elucidated, much less is known about the precursors, the underlying transcriptional program and the dynamics of the other macrophages in the central nervous system (CNS). It was assumed that they have a high turnover from blood-borne monocytes. However, using parabiosis and fate-mapping approaches in mice, we found that CNS macrophages arose from hematopoietic precursors during embryonic development and established stable populations, with the notable exception of choroid plexus macrophages, which had dual origins and a shorter life span...
July 2016: Nature Immunology
Yaming Wang, Tyler K Ulland, Jason D Ulrich, Wilbur Song, John A Tzaferis, Justin T Hole, Peng Yuan, Thomas E Mahan, Yang Shi, Susan Gilfillan, Marina Cella, Jaime Grutzendler, Ronald B DeMattos, John R Cirrito, David M Holtzman, Marco Colonna
Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial receptor that recognizes changes in the lipid microenvironment, which may occur during amyloid β (Aβ) accumulation and neuronal degeneration in Alzheimer's disease (AD). Rare TREM2 variants that affect TREM2 function lead to an increased risk of developing AD. In murine models of AD, TREM2 deficiency prevents microglial clustering around Aβ deposits. However, the origin of myeloid cells surrounding amyloid and the impact of TREM2 on Aβ accumulation are a matter of debate...
May 2, 2016: Journal of Experimental Medicine
Ryoichi Tashima, Satsuki Mikuriya, Daisuke Tomiyama, Miho Shiratori-Hayashi, Tomohiro Yamashita, Yuta Kohro, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue, Makoto Tsuda
Accumulating evidence indicates that peripheral nerve injury (PNI) activates spinal microglia that are necessary for neuropathic pain. Recent studies using bone marrow (BM) chimeric mice have reported that after PNI, circulating BM-derived cells infiltrate into the spinal cord and differentiate into microglia-like cells. This raises the possibility that the population of spinal microglia after PNI may be heterogeneous. However, the infiltration of BM cells in the spinal cord remains controversial because of experimental adverse effects of strong irradiation used for generating BM chimeric mice...
2016: Scientific Reports
Serena Y S Tan, Mark A Krasnow
Macrophages are specialized phagocytic cells, present in all tissues, which engulf and digest pathogens, infected and dying cells, and debris, and can recruit and regulate other immune cells and the inflammatory response and aid in tissue repair. Macrophage subpopulations play distinct roles in these processes and in disease, and are typically recognized by differences in marker expression, immune function, or tissue of residency. Although macrophage subpopulations in the brain have been found to have distinct developmental origins, the extent to which development contributes to macrophage diversity between tissues and within tissues is not well understood...
April 15, 2016: Development
Benjamin A Olenchock, Javid Moslehi, Alan H Baik, Shawn M Davidson, Jeremy Williams, William J Gibson, Abhishek A Chakraborty, Kerry A Pierce, Christine M Miller, Eric A Hanse, Ameeta Kelekar, Lucas B Sullivan, Amy J Wagers, Clary B Clish, Matthew G Vander Heiden, William G Kaelin
Ischemic preconditioning is the phenomenon whereby brief periods of sublethal ischemia protect against a subsequent, more prolonged, ischemic insult. In remote ischemic preconditioning (RIPC), ischemia to one organ protects others organs at a distance. We created mouse models to ask if inhibition of the alpha-ketoglutarate (αKG)-dependent dioxygenase Egln1, which senses oxygen and regulates the hypoxia-inducible factor (HIF) transcription factor, could suffice to mediate local and remote ischemic preconditioning...
February 25, 2016: Cell
Takashi Kawano, Satoru Eguchi, Hideki Iwata, Daiki Yamanaka, Hiroki Tateiwa, Fabricio M Locatelli, Masataka Yokoyama
AIMS: The present study aimed to explore the preventive or therapeutic effect of peri-operative pregabalin treatment on the memory deficits and related hippocampal inflammation following surgery in aged rats. MAIN METHODS: Aged rats underwent abdominal or sham surgery, and were then divided into 2 groups, either early or late pregabalin treatment. Fourteen days after surgery, the cognitive function was assessed using novel object recognition test, followed by measurement of hippocampal cytokines and voltage-dependent calcium channel α2δ subunit (CACNA2D1)...
March 1, 2016: Life Sciences
Revanth Kosaraju, Robert C Rennert, Zeshaan N Maan, Dominik Duscher, Janos Barrera, Alexander J Whittam, Michael Januszyk, Jayakumar Rajadas, Melanie Rodrigues, Geoffrey C Gurtner
Adipose-derived mesenchymal stem cells (ASCs) are appealing for cell-based wound therapies because of their accessibility and ease of harvest, but their utility is limited by poor cell survival within the harsh wound microenvironment. In prior work, our laboratory has demonstrated that seeding ASCs within a soft pullulan-collagen hydrogel enhances ASC survival and improves wound healing. To more fully understand the mechanism of this therapy, we examined whether ASC-seeded hydrogels were able to modulate the recruitment and/or functionality of endogenous progenitor cells...
February 2016: Tissue Engineering. Part A
Yusuke Matsuo, Fumitaka Mizoguchi, Tetsuya Saito, Kimito Kawahata, Satoshi Ueha, Kouji Matsushima, Yutaka Inagaki, Nobuyuki Miyasaka, Hitoshi Kohsaka
Synovial fibroblasts play crucial roles in inflammation and joint destruction in rheumatoid arthritis (RA). How they accumulate in the RA joints remains unclear. This study was conducted to discern whether cellular influx from the outside of the joints and local proliferation are responsible for synovial fibroblast accumulation in an animal model of RA. We found that synovial fibroblasts were identified as GFP+ cells using collagen type I alpha 2 (Col1a2)-GFP transgenic reporter mice. Then, bone marrow transplantation and parabiosis techniques were utilized to study the cellular influx...
February 12, 2016: Biochemical and Biophysical Research Communications
Nathan A DeCarolis, Elizabeth D Kirby, Tony Wyss-Coray, Theo D Palmer
Aging is strongly correlated with decreases in neurogenesis, the process by which neural stem and progenitor cells proliferate and differentiate into new neurons. In addition to stem-cell-intrinsic factors that change within the aging stem-cell pool, recent evidence emphasizes new roles for systemic and microenvironmental factors in modulating the neurogenic niche. This article focuses on new insights gained through the use of heterochronic parabiosis models, in which an old mouse and a young circulatory system are joined...
December 2015: Cold Spring Harbor Perspectives in Medicine
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