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Ana Aires, Maria Dos Anjos Teixeira, Catarina Lau, Cláudia Moreira, Ana Spínola, Alexandra Mota, Inês Freitas, Jorge Coutinho, Margarida Lima
Background: Immunophenotypic analysis of the bone marrow (BM) cells has proven to be helpful in the diagnosis of Myelodysplastic Syndromes (MDS). However, the usefulness of flow cytometry (FCM) for the detection of myelodysplasia in the peripheral blood (PB) still needs to be investigated. The aim of this pilot study was to evaluate the value of FCM-based PB neutrophil and monocyte immunophenotyping for the diagnosis of lower risk MDS (LR-MDS). Methods: We evaluated by 8-color FCM the expression of multiple cell surface molecules (CD10, CD11b, CD11c, CD13, CD14, CD15, CD16, CD34, CD45, CD56, CD64 and HLA-DR) in PB neutrophils and monocytes from a series of 14 adult LR-MDS patients versus 14 normal individuals...
2018: BMC Hematology
Ping-An Zhang, Hong-Yan Zhu, Qi-Ya Xu, Wan-Jie Du, Shufen Hu, Guang-Yin Xu
Aims Insular cortex is a brain region critical for processing of the sensation. Purinergic receptors are involved in the formation of chronic pain. The aim of the present study was to explore the role and mechanism of P2X3 receptors (P2X3Rs) in insular cortex in chronic visceral pain. Methods Chronic visceral pain in adult rats was induced by neonatal maternal deprivation and measured by detecting the threshold of colorectal distension. Western blotting, immunofluorescence, and real-time quantitative polymerase chain reaction techniques were used to detect the expression and distribution of P2X3Rs...
January 2018: Molecular Pain
Srikant Rangaraju, Syed Ali Raza, Noel Xiang'An Li, Ranjita Betarbet, Eric B Dammer, Duc Duong, James J Lah, Nicholas T Seyfried, Allan I Levey
In the central nervous system (CNS), microglia are innate immune mononuclear phagocytes (CNS MPs) that can phagocytose infectious particles, apoptotic cells, neurons, and pathological protein aggregates, such as Aβ in Alzheimer's disease (AD). While CD11b+ CD45low microglia account for the majority of CNS MPs, a small population of CD11b+ CD45high CNS MPs is also recognized in AD that surround Aβ plaques. These transcriptionally and pathologically unique CD45high cells have unclear origin and undefined phagocytic characteristics...
2018: Frontiers in Immunology
Hong Jun Park, Jiye Kim, Fatema Tuj Saima, Ki-Jong Rhee, Soonjae Hwang, Moon Young Kim, Soon Koo Baik, Young Woo Eom, Hyun-Soo Kim
Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to intestinal microbes in an individual with a genetic predisposition. Therefore, alleviation of inflammation is very important to treat IBD. Mesenchymal stem cells (MSCs) have been highlighted as new candidates for treating autoimmune disease based on their immunomodulatory properties. In this study, we investigated the anti-inflammatory mechanism and therapeutic effects of adipose tissue-derived MSCs (ASCs) using THP-1 macrophages and dextran sodium sulfate (DSS)-induced mice with chronic colitis...
March 15, 2018: Biochemical and Biophysical Research Communications
Nicholas Beazley-Long, Catherine Elizabeth Moss, William Robert Ashby, Samuel Marcus Bestall, Fatimah Almahasneh, Alexandra Margaret Durrant, Andrew Vaughan Benest, Zoe Blackley, Kurt Ballmer-Hofer, Masanori Hirashima, Richard Phillip Hulse, David Owen Bates, Lucy Frances Donaldson
Chronic pain can develop in response to conditions such as inflammatory arthritis. The central mechanisms underlying the development and maintenance of chronic pain in humans are not well elucidated although there is evidence for a role of microglia and astrocytes. However in pre-clinical models of pain, including models of inflammatory arthritis, there is a wealth of evidence indicating roles for pathological glial reactivity within the CNS. In the spinal dorsal horn of rats with painful inflammatory arthritis we found both a significant increase in CD11b+ microglia-like cells and GFAP+ astrocytes associated with blood vessels, and the number of activated blood vessels expressing the adhesion molecule ICAM-1, indicating potential glio-vascular activation...
March 13, 2018: Brain, Behavior, and Immunity
Jonatan Barrera-Chimal, Gabriel R Estrela, Sebastian M Lechner, Sébastien Giraud, Soumaya El Moghrabi, Shiem Kaaki, Peter Kolkhof, Thierry Hauet, Frédéric Jaisser
Acute kidney injury induced by ischemia/reperfusion is an independent risk factor for chronic kidney disease. Macrophage recruitment plays an essential role during the injury and repair phases after an ischemic episode in the kidney. Here we show that the novel non-steroidal mineralocorticoid receptor antagonist finerenone or selective myeloid mineralocorticoid receptor ablation protects against subsequent chronic dysfunction and fibrosis induced by an episode of bilateral kidney ischemia/reperfusion in mice...
March 13, 2018: Kidney International
Vu Huy Luong, Takenao Chino, Noritaka Oyama, Takashi Matsushita, Yoko Sasaki, Dai Ogura, Shin-Ichiro Niwa, Tanima Biswas, Akiyuki Hamasaki, Mikako Fujita, Yoshinari Okamoto, Masami Otsuka, Hironobu Ihn, Minoru Hasegawa
BACKGROUND: Transforming growth factor-β (TGF-β)/Smad signaling is well known to play a critical role in the pathogenesis of systemic sclerosis (SSc). We previously developed an artificial molecule, the histidine-pyridine-histidine ligand derivative HPH-15, which may have an antifibrotic effect. The purpose of the present study was to clarify the effects of this drug in human skin fibroblasts and in a preclinical model of SSc. METHODS: The effects of HPH-15 on expression of extracellular matrix components and TGF-β signaling in human dermal fibroblasts were analyzed...
March 15, 2018: Arthritis Research & Therapy
Takuya Tsubaki, Tetsuya Kadonosono, Shimon Sakurai, Tadashi Shiozawa, Toshiki Goto, Shiori Sakai, Takahiro Kuchimaru, Takeharu Sakamoto, Hitomi Watanabe, Gen Kondoh, Shinae Kizaka-Kondoh
The immunosuppressive tumor microenvironment is a hallmark of cancer. Myeloid-derived suppressor cells (MDSCs) are CD11b+ Gr-1+ tumor-infiltrating immature myeloid cells that strongly mediate tumor immunosuppression. The CD11b+ Gr-1+ cells are a heterogeneous cell population, and the impacts of each subpopulation on tumor progression are not yet completely understood. In the present study, we identified a novel subpopulation of CD11b+ Gr-1+ cells from murine lung carcinoma tumors according to their strongly adherent abilities...
February 16, 2018: Oncotarget
Valeryi K Lishko, Valentin P Yakubenko, Tatiana P Ugarova, Nataly P Podolnikova
Platelet Factor 4 (PF4) is one of the most abundant cationic proteins secreted from α-granules of activated platelets. Based on its structure, PF4 was assigned to the CXC family of chemokines and has been shown to have numerous effects on myeloid leukocytes. However, the receptor for PF4 remains unknown. Here, we demonstrate that PF4 induces leukocyte responses through the integrin Mac-1 (αM β2 , CD11b/CD18). Human neutrophils, monocytes, U937 monocytic and HEK293 cells expressing Mac-1 strongly adhered to immobilized PF4 in a concentration-dependent manner...
March 14, 2018: Journal of Biological Chemistry
Justine M Abais-Battad, Hayley Lund, Daniel J Fehrenbach, John Henry Dasinger, David L Mattson
The current study, performed in Dahl Salt-Sensitive (SS) and SS-Rag1-/- rats lacking T- and B- lymphocytes, tested the hypothesis that immune cells amplify salt-sensitive hypertension and kidney damage in response to a high protein diet. After weaning, SS and SS-Rag1-/- rats were placed on an isocaloric, 0.4% NaCl diet containing normal (18%) or high (30%) protein. At 9 weeks of age, rats were switched to a 4.0% NaCl diet containing the same amount of dietary protein and maintained on the high salt diet for 3 weeks...
March 14, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Alfredo Perales-Puchalt, Jairo Perez-Sanz, Kyle K Payne, Nikolaos Svoronos, Michael J Allegrezza, Ricardo A Chaurio, Carmen Anadon, Joseph Calmette, Subir Biswas, Jessica A Mine, Tara Lee Costich, Logan Nickels, Jayamanna Wickramasinghe, Melanie R Rutkowski, Jose R Conejo-Garcia
Due to their cytotoxic activities, many anticancer drugs cause extensive damage to the intestinal mucosa and have antibiotic activities. Here, we show that cisplatin induces significant changes in the repertoire of intestinal commensal bacteria that exacerbate mucosal damage. Restoration of the microbiota through fecal-pellet gavage drives healing of cisplatin-induced intestinal damage. Bacterial translocation to the blood stream is correspondingly abrogated, resulting in a significant reduction in systemic inflammation, as evidenced by decreased serum IL-6 and reduced mobilization of granulocytes...
March 14, 2018: Journal of Leukocyte Biology
Claudia Brockmann, Norbert Kociok, Sabrina Dege, Anja-Maria Davids, Tobias Brockmann, Kelly R Miller, Antonia M Joussen
PURPOSE: To assess the influence of retinal macrophages and microglia on the formation of choroidal neovascularization (CNV). Therefore, we used a transgenic mouse (CD11b-HSVTK) in which the application of ganciclovir (GCV) results in a depletion of CD11b+ cells. METHODS: We first investigated if a local depletion of CD11b+ macrophages and microglia in the retina is feasible. In a second step, the influence of CD11b+ cell depletion on CNV formation was analysed...
March 14, 2018: Acta Ophthalmologica
Liya Pi, Chunhua Fu, Yuanquing Lu, Junmei Zhou, Marda Jorgensen, Vinayak Shenoy, Kenneth E Lipson, Edward W Scott, Andrew J Bryant
Chronic hypoxia frequently complicates the care of patients with interstitial lung disease, contributing to the development of pulmonary hypertension (PH), and premature death. Connective tissue growth factor (CTGF), a matricellular protein of the Cyr61/CTGF/Nov (CCN) family, is known to exacerbate vascular remodeling within the lung. We have previously demonstrated that vascular endothelial-cell specific down-regulation of CTGF is associated with protection against the development of PH associated with hypoxia, though the mechanism for this effect is unknown...
2018: Frontiers in Physiology
Takeshi Shimoide, Naoyuki Kawao, Yukinori Tamura, Kiyotaka Okada, Yoshitaka Horiuchi, Katsumi Okumoto, Shinji Kurashimo, Masayoshi Ishida, Kohei Tatsumi, Osamu Matsuo, Hiroshi Kaji
Delayed fracture healing is a significant clinical problem among various complications in diabetic patients. However, the details in the mechanisms of diabetic delayed bone repair have still remained unknown. Here, we investigated the roles of macrophages in diabetic delayed bone repair after femoral bone injury using streptozotocin (STZ)-treated or plasminogen activator inhibitor-1 (PAI-1)-deficient female mice. STZ treatment significantly decreased the numbers of F4/80-positive cells (macrophages), but not Gr-1-positive cells (neutrophils), at the damaged site on day 2 after femoral bone injury in mice...
March 8, 2018: Endocrinology
Karin de Ruiter, Selma van Staveren, Bart Hilvering, Edward Knol, Nienke Vrisekoop, Leo Koenderman, Maria Yazdanbakhsh
Upon activation granulocytes upregulate several adhesion molecules (CD11b) and granule proteins (CD35, CD66b) and shed surface l-selectin (CD62L). These changes in expression, as assessed by flow cytometry, can be used as markers for activation. Whereas these markers are usually studied in fresh blood samples, a new method is required when samples are collected at a field site with no direct access to a flow cytometer. Therefore, we developed and tested a field-applicable method in which fixed leukocytes were cryopreserved...
March 13, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Zhuan Li, Jie Zhao, Shujun Zhang, Steven A Weinman
Alcohol consumption is generally well tolerated by the liver but in some individuals it results in persistent inflammation and liver disease. The mechanisms that regulate alcohol-induced liver inflammation are poorly understood. The transcription factor FOXO3 has previously been shown to be involved in suppressing alcohol-induced liver injury. In this study we demonstrate that in response to alcohol, approximately 10% of mouse hepatic macrophages undergo FOXO3-dependent apoptosis. By 3 days of alcohol exposure total hepatic macrophage numbers declined by 30% but these were restored to normal after 10 days of continued exposure...
December 2018: Cell Death Discovery
Hui-Lun Lu, Xin-Yan Huang, Yi-Feng Luo, Wei-Ping Tan, Pei-Fen Chen, Yu-Biao Guo
The goal of this study was to investigate the role of M1 macrophages in acute lung injury (ALI). To address this, we used LPS-treated wildtype and CD11b-DTR mice, and examined their M1 macrophage levels, and the extent of their inflammation and pulmonary injuries. In addition, we evaluated pulmonary function by measuring the expressions of SP-A and SP-B in infiltrated M1 macrophages. Finally, we co-cultured the mouse type II-like alveolar epithelial cells (AT-II) and mouse pulmonary microvascular endothelial cells (PMECs) with M1 macrophages in the presence of TNF-α or H2 O2 and assessed them for viability and apoptosis...
March 12, 2018: Bioscience Reports
Yaling Liu, Tulika Sharma, I-Ping Chen, Ernst Reichenberger, Yasuyoshi Ueki, Yumna Arif, Daniel Parisi, Peter Maye
We utilized a bone marrow stromal culture system to investigate changes in TGFβ signaling in a mouse model for cherubism (Sh3bp2KI/KI ). Interestingly, bone marrow cultures derived from cherubism mice not only displayed impaired osteoblast differentiation, but also had spontaneous osteoclast formation. PAI1, a target gene of TGFβ signaling, was elevated 2-fold in cherubism CD11b- ,CD45- cells compared to wild type cells, while the expression of BAMBI, an inhibitor of TGFβ signaling, was down-regulated. We also discovered that treatment of cherubism cultures with antagonists of the TGFβ signaling pathway could largely rescue osteoblast differentiation and markedly reduce spontaneous osteoclast formation...
March 9, 2018: Bone
Tadahiro Miyake, Duo Wang, Hidetada Matsuoka, Kentaro Morita, Hiroshi Yasuda, Kazuhiro Yatera, Tamotsu Kanazawa, Yasuhiro Yoshida
Particulate matter (PM) with a median diameter <2.5 μm, is associated with respiratory and cardiovascular diseases. We previously reported the biological effects of PM in vivo, and although neutrophils play an important role in initiating inflammation, few reports have focused on the relationship between PM inhalation and immune responses. Here, we investigated the effect of PM particle size on neutrophils, including their endocytosis activity and reactive oxygen species (ROS) production. Flow cytometry analysis indicated that 1 μm particles are readily endocytosed by neutrophils and that endocytosis is reduced at 4 °C...
March 6, 2018: International Immunopharmacology
Petr Dubový, Ilona Klusáková, Ivana Hradilová-Svíženská, Marek Joukal, Pere Boadas-Vaello
Peripheral nerve injuries (PNIs) may result in cellular and molecular changes in supraspinal structures possibly involved in neuropathic pain (NPP) maintenance. Activated glial cells in specific supraspinal subregions may affect the facilitatory role of descending pathways. Sterile chronic compression injury (sCCI) and complete sciatic nerve transection (CSNT) in rats were used as NPP models to study the activation of glial cells in the subregions of periaqueductal gray (PAG) and rostral ventromedial medulla (RVM)...
2018: Frontiers in Cellular Neuroscience
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