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Sample records for macrophage recruitment primes

  1. IFN-γ priming of macrophages represses a part of the inflammatory program and attenuates neutrophil recruitment

    NARCIS (Netherlands)

    Hoeksema, Marten A.; Scicluna, Brendon P.; Boshuizen, Marieke C. S.; van der Velden, Saskia; Neele, Annette E.; van den Bossche, Jan; Matlung, Hanke L.; van den Berg, Timo K.; Goossens, Pieter; de Winther, Menno P. J.

    2015-01-01

    Macrophages form a heterogeneous population of immune cells, which is critical for both the initiation and resolution of inflammation. They can be skewed to a proinflammatory subtype by the Th1 cytokine IFN-γ and further activated with TLR triggers, such as LPS. In this work, we investigated the

  2. DMPD: Genetic regulation of macrophage priming/activation: the Lsh gene story. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 1757110 Genetic regulation of macrophage priming/activation: the Lsh gene story. Bl... (.svg) (.html) (.csml) Show Genetic regulation of macrophage priming/activation: the Lsh gene story. Pubmed...ID 1757110 Title Genetic regulation of macrophage priming/activation: the Lsh gen

  3. Recruiting specialized macrophages across the borders to restore brain functions.

    Science.gov (United States)

    Corraliza, Inés

    2014-01-01

    Although is well accepted that the central nervous system has an immune privilege protected by the blood-brain barrier (BBB) and maintained by the glia, it is also known that in homeostatic conditions, peripheral immune cells are able to penetrate to the deepest regions of brain without altering the structural integrity of the BBB. Nearly all neurological diseases, including degenerative, autoimmune or infectious ones, compromising brain functions, develop with a common pattern of inflammation in which macrophages and microglia activation have been regarded often as the "bad guys." However, recognizing the huge heterogeneity of macrophage populations and also the different expression properties of microglia, there is increasing evidence of alternative conditions in which these cells, if primed and addressed in the correct direction, could be essential for reparative and regenerative functions. The main proposal of this review is to integrate studies about macrophage's biology at the brain borders where the ultimate challenge is to penetrate through the BBB and contribute to change or even stop the course of disease. Thanks to the efforts made in the last century, this special wall is currently recognized as a highly regulated cooperative structure, in which their components form neurovascular units. This new scenario prompted us to review the precise cross-talk between the mind and body modes of immune response.

  4. Small cell lung cancer: Recruitment of macrophages by circulating tumor cells.

    Science.gov (United States)

    Hamilton, Gerhard; Rath, Barbara; Klameth, Lukas; Hochmair, Maximilan J

    2016-03-01

    Tumor-associated macrophages (TAMs) play an important role in tumor progression, suppression of antitumor immunity and dissemination. Blood monocytes infiltrate the tumor region and are primed by local microenvironmental conditions to promote tumor growth and invasion. Although many of the interacting cytokines and factors are known for the tumor-macrophage interactions, the putative contribution of circulating tumor cells (CTCs) is not known so far. These specialized cells are characterized by increased mobility, ability to degrade the extracellular matrix (ECM) and to enter the blood stream and generate secondary lesions which is a leading cause of death for the majority of tumor patients. The first establishment of two permanent CTC lines, namely BHGc7 and 10, from blood samples of advanced stage small cell lung cancer (SCLC) patients allowed us to investigate the CTC-immune cell interaction. Cocultures of peripheral blood mononuclear cells (PBMNCs) with CTCs or addition of CTC-conditioned medium (CTC-CM) in vitro resulted in monocyte-macrophage differentiation and appearance of CD14 + , CD163 weak and CD68 + macrophages expressing markers of TAMs. Furthermore, we screened the supernatants of CTC-primed macrophages for presence of approximately 100 cytokines and compared the expression with those induced by the local metastatic SCLC26A cell line. Macrophages recruited by SCLC26A-CM showed expression of osteopontin (OPN), monocyte chemoattractant protein-1 (MCP-1), IL-8, chitinase3-like 1 (CHI3L1), platelet factor (Pf4), IL-1ra and matrix metalloproteinase-9 (MMP-9) among other minor cytokines/chemokines. In contrast, BHGc7-CM induced marked overexpression of complement factor D (CFD)/adipsin and vitamin D-BP (VDBP), as well as increased secretion of OPN, lipocalin-2 (LCN2), CHI3L1, uPAR, MIP-1 and GDF-15/MIC-1. BHGc10, derived independently from relapsed SCLC, revealed an almost identical pattern with added expression of ENA-78/CXCL5. CMs of the non-tumor HEK293

  5. Granulocyte-macrophage colony-stimulating factor primes interleukin-13 production by macrophages via protease-activated receptor-2.

    Science.gov (United States)

    Aoki, Manabu; Yamaguchi, Rui; Yamamoto, Takatoshi; Ishimaru, Yasuji; Ono, Tomomichi; Sakamoto, Arisa; Narahara, Shinji; Sugiuchi, Hiroyuki; Hirose, Eiji; Yamaguchi, Yasuo

    2015-04-01

    Chronic inflammation is often linked to the presence of type 2-polarized macrophages, which are induced by the T helper type 2 cytokines interleukin-4 and interleukin-13 (IL-13). IL-13 is a key mediator of tissue fibrosis caused by T helper type 2-based inflammation. Human neutrophil elastase (HNE) plays a pivotal role in the pathogenesis of pulmonary fibrosis. This study investigated the priming effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on IL-13 expression by macrophages stimulated with HNE. Adherent macrophages were obtained from primary cultures of human mononuclear cells. Expression of IL-13 mRNA and protein by GM-CSF-dependent macrophages was investigated after stimulation with HNE, using the polymerase chain reaction and enzyme-linked immunosorbent assay. GM-CSF had a priming effect on IL-13 mRNA and protein expression by macrophages stimulated with HNE, while this effect was not observed for various other cytokines. GM-CSF-dependent macrophages showed a significant increase in the expression of protease activated receptor-2 (PAR-2) mRNA and protein. The response of IL-13 mRNA to HNE was significantly decreased by pretreatment with alpha1-antitrypsin, a PAR-2 antibody (SAM11), or a PAR-2 antagonist (ENMD-1068). These findings suggest that stimulation with HNE can induce IL-13 production by macrophages, especially GM-CSF-dependent macrophages. Accordingly, neutrophil elastase may have a key role in fibrosis associated with chronic inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. A defect in the inflammation-primed macrophage-activation cascade in osteopetrotic rats.

    Science.gov (United States)

    Yamamoto, N; Lindsay, D D; Naraparaju, V R; Ireland, R A; Popoff, S N

    1994-05-15

    Macrophages were activated by administration of lysophosphatidylcholine (lyso-Pc) or dodecylglycerol (DDG) to wild-type rats but not in osteopetrotic (op) mutant rats. In vitro treatment of wild-type rat peritoneal cells with lyso-Pc or DDG efficiently activated macrophages whereas treatment of op mutant rat peritoneal cells with lyso-Pc or DDG did not activate macrophages. The inflammation-primed macrophage activation cascade in rats requires participation of B lymphocytes and vitamin D binding protein (DBP). Lyso-Pc-inducible beta-galactosidase of wild-type rat B lymphocytes can convert DBP to the macrophage-activating factor (MAF), whereas B lymphocytes of the op mutant rats were shown to be deficient in lyso-Pc-inducible beta-galactosidase. DBP is conserved among mammalian species. Treatment of human DBP (Gc1 protein) with commercial glycosidases yields an extremely high titrated MAF as assayed on mouse and rat macrophages. Because the enzymatically generated MAF (GcMAF) bypasses the role of lymphocytes in macrophage activation, the op mutant rat macrophages were efficiently activated by administration of a small quantity (100 pg/rat) of GcMAF. Likewise, in vitro treatment of op rat peritoneal cells with as little as 40 pg GcMAF/ml activated macrophages.

  7. Recruitment of mesenchymal stem cells and macrophages by dual release of stromal cell-derived factor-1 and a macrophage recruitment agent enhances wound closure.

    Science.gov (United States)

    Kim, Yang-Hee; Tabata, Yasuhiko

    2016-04-01

    In this study, the wound closure of mouse skin defects was examined in terms of recruitment of mesenchymal stem cells (MSC) and macrophages. For the cells recruitment, stromal derived factor-1 (SDF-1) of a MSC recruitment agent and sphingosine-1 phosphate agonist (SEW2871) of a macrophages recruitment agent were incorporated into gelatin hydrogels, and then released in a controlled fashion. When applied to a skin wound defect of mice, gelatin hydrogels incorporating mixed 500 ng SDF-1 and 0.4, 0.8, or 1.6 mg SEW2871-micelles recruited a higher number of both MSC and macrophages than those incorporating SDF-1 or phosphate buffered saline. However, the number of M1 phenotype macrophages for the hydrogel incorporating mixed SDF-1 and SEW2871-micelles recruited was remarkably low to a significant extent compared with that for those hydrogel incorporating 0.4, 0.8, or 1.6 mg SEW2871-micelles. On the other hand, the number of M2 macrophages 3 days after the implantation of the hydrogels incorporating SDF-1 and 0.4 mg SEW2871-micelles significantly increased compared with that for other hydrogels. In vivo experiments revealed the hydrogels incorporating SDF-1 and 0.4 mg SEW2871-micelles promoted the wound closure of skin defect to a significant stronger extent than those incorporating SEW2871-micelles, SDF-1, and a mixture of SDF-1 and higher doses of SEW2871-micelles. It is concluded that the in vivo recruitment of MSC and macrophages to the defects may contribute to the tissue regeneration of skin wound. © 2016 Wiley Periodicals, Inc.

  8. 5-Lipoxygenase-Dependent Recruitment of Neutrophils and Macrophages by Eotaxin-Stimulated Murine Eosinophils

    Directory of Open Access Journals (Sweden)

    Ricardo Alves Luz

    2014-01-01

    Full Text Available The roles of eosinophils in antimicrobial defense remain incompletely understood. In ovalbumin-sensitized mice, eosinophils are selectively recruited to the peritoneal cavity by antigen, eotaxin, or leukotriene(LTB4, a 5-lipoxygenase (5-LO metabolite. 5-LO blockade prevents responses to both antigen and eotaxin. We examined responses to eotaxin in the absence of sensitization and their dependence on 5-LO. BALB/c or PAS mice and their mutants (5-LO-deficient ALOX; eosinophil-deficient GATA-1 were injected i.p. with eotaxin, eosinophils, or both, and leukocyte accumulation was quantified up to 24 h. Significant recruitment of eosinophils by eotaxin in BALB/c, up to 24 h, was accompanied by much larger numbers of recruited neutrophils and monocytes/macrophages. These effects were abolished by eotaxin neutralization and 5-LO-activating protein inhibitor MK886. In ALOX (but not PAS mice, eotaxin recruitment was abolished for eosinophils and halved for neutrophils. In GATA-1 mutants, eotaxin recruited neither neutrophils nor macrophages. Transfer of eosinophils cultured from bone-marrow of BALB/c donors, or from ALOX donors, into GATA-1 mutant recipients, i.p., restored eotaxin recruitment of neutrophils and showed that the critical step dependent on 5-LO is the initial recruitment of eosinophils by eotaxin, not the secondary neutrophil accumulation. Eosinophil-dependent recruitment of neutrophils in naive BALB/c mice was associated with increased binding of bacteria.

  9. Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy.

    Directory of Open Access Journals (Sweden)

    Degang Yang

    2016-01-01

    Full Text Available The persistence of Mycobacterium leprae (M. leprae infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-infected macrophages might have altered immune functions.Here, we treated monocyte-derived macrophages with live or killed M. leprae, and examined their activation status and antigen presentation. We found that macrophages treated with live M. leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta, IL-6, tumor necrosis factor alpha (TNF-alpha and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M. leprae preferentially primed regulatory T (Treg cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma expression and CD8+ T cell cytotoxicity were reduced. Chromium release assay also found that live M. leprae-treated macrophages were more resistant to CD8+ T cell-mediated cytotoxicity than sonicated M. leprae-treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings.Together, our data demonstrate that M. leprae could utilize infected macrophages by two mechanisms: firstly, M. leprae-infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M. leprae-infected macrophages were more effective at evading CD8+ T cell-mediated cytotoxicity.

  10. Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy.

    Science.gov (United States)

    Yang, Degang; Shui, Tiejun; Miranda, Jake W; Gilson, Danny J; Song, Zhengyu; Chen, Jia; Shi, Chao; Zhu, Jianyu; Yang, Jun; Jing, Zhichun

    2016-01-01

    The persistence of Mycobacterium leprae (M. leprae) infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-infected macrophages might have altered immune functions. Here, we treated monocyte-derived macrophages with live or killed M. leprae, and examined their activation status and antigen presentation. We found that macrophages treated with live M. leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha) and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M. leprae preferentially primed regulatory T (Treg) cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma) expression and CD8+ T cell cytotoxicity were reduced. Chromium release assay also found that live M. leprae-treated macrophages were more resistant to CD8+ T cell-mediated cytotoxicity than sonicated M. leprae-treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings. Together, our data demonstrate that M. leprae could utilize infected macrophages by two mechanisms: firstly, M. leprae-infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M. leprae-infected macrophages were more effective at evading CD8+ T cell-mediated cytotoxicity.

  11. Cell Origin Dictates Programming of Resident versus Recruited Macrophages during Acute Lung Injury.

    Science.gov (United States)

    Mould, Kara J; Barthel, Lea; Mohning, Michael P; Thomas, Stacey M; McCubbrey, Alexandra L; Danhorn, Thomas; Leach, Sonia M; Fingerlin, Tasha E; O'Connor, Brian P; Reisz, Julie A; D'Alessandro, Angelo; Bratton, Donna L; Jakubzick, Claudia V; Janssen, William J

    2017-09-01

    Two populations of alveolar macrophages (AMs) coexist in the inflamed lung: resident AMs that arise during embryogenesis, and recruited AMs that originate postnatally from circulating monocytes. The objective of this study was to determine whether origin or environment dictates the transcriptional, metabolic, and functional programming of these two ontologically distinct populations over the time course of acute inflammation. RNA sequencing demonstrated marked transcriptional differences between resident and recruited AMs affecting three main areas: proliferation, inflammatory signaling, and metabolism. Functional assays and metabolomic studies confirmed these differences and demonstrated that resident AMs proliferate locally and are governed by increased tricarboxylic acid cycle and amino acid metabolism. Conversely, recruited AMs produce inflammatory cytokines in association with increased glycolytic and arginine metabolism. Collectively, the data show that even though they coexist in the same environment, inflammatory macrophage subsets have distinct immunometabolic programs and perform specialized functions during inflammation that are associated with their cellular origin.

  12. Hemoglobin induces monocyte recruitment and CD163-macrophage polarization in abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Rubio-Navarro, Alfonso; Amaro Villalobos, Juan Manuel; Lindholt, Jes S

    2015-01-01

    BACKGROUND: Increased hemoglobin (Hb) accumulation was reported in abdominal aortic aneurysms (AAAs). CD163 is a macrophage receptor involved in tissue Hb clearance, however its role in AAA has not been reported. We investigated the role of Hb on monocyte recruitment and differentiation towards CD......163 expressing macrophages ex vivo, in vitro and in human AAA. METHODS AND RESULTS: CD163 mRNA and protein expression was significantly higher in human AAA (n=7) vs. healthy wall (n=6). CD163 was predominantly found in adventitia of AAA, coinciding with areas rich in hemosiderin and adjacent...

  13. Macrophage recruitment by fibrocystin-defective biliary epithelial cells promotes portal fibrosis in congenital hepatic fibrosis.

    Science.gov (United States)

    Locatelli, Luigi; Cadamuro, Massimiliano; Spirlì, Carlo; Fiorotto, Romina; Lecchi, Silvia; Morell, Carola Maria; Popov, Yury; Scirpo, Roberto; De Matteis, Maria; Amenduni, Mariangela; Pietrobattista, Andrea; Torre, Giuliano; Schuppan, Detlef; Fabris, Luca; Strazzabosco, Mario

    2016-03-01

    Congenital hepatic fibrosis (CHF) is a disease of the biliary epithelium characterized by bile duct changes resembling ductal plate malformations and by progressive peribiliary fibrosis, in the absence of overt necroinflammation. Progressive liver fibrosis leads to portal hypertension and liver failure; however, the mechanisms leading to fibrosis in CHF remain elusive. CHF is caused by mutations in PKHD1, a gene encoding for fibrocystin, a ciliary protein expressed in cholangiocytes. Using a fibrocystin-defective (Pkhd1(del4/del4)) mouse, which is orthologous of CHF, we show that Pkhd1(del4/del4) cholangiocytes are characterized by a β-catenin-dependent secretion of a range of chemokines, including chemokine (C-X-C motif) ligands 1, 10, and 12, which stimulate bone marrow-derived macrophage recruitment. We also show that Pkhd1(del4/del4) cholangiocytes, in turn, respond to proinflammatory cytokines released by macrophages by up-regulating αvβ6 integrin, an activator of latent local transforming growth factor-β1. While the macrophage infiltrate is initially dominated by the M1 phenotype, the profibrogenic M2 phenotype increases with disease progression, along with the number of portal myofibroblasts. Consistent with these findings, clodronate-induced macrophage depletion results in a significant reduction of portal fibrosis and portal hypertension as well as of liver cysts. Fibrosis can be initiated by an epithelial cell dysfunction, leading to low-grade inflammation, macrophage recruitment, and collagen deposition; these findings establish a new paradigm for biliary fibrosis and represent a model to understand the relationship between cell dysfunction, parainflammation, liver fibrosis, and macrophage polarization over time. © 2015 by the American Association for the Study of Liver Diseases.

  14. Recruitment of macrophages from the spleen contributes to myocardial fibrosis and hypertension induced by angiotensin II

    Directory of Open Access Journals (Sweden)

    Ning-Ping Wang

    2017-05-01

    Full Text Available Introduction: The purpose of this study was to determine whether macrophages migrated from the spleen are associated with angiotensin II-induced cardiac fibrosis and hypertension. Methods: Sprague-Dawley rats were subjected to angiotensin II infusion in vehicle (500 ng/kg/min for up to four weeks. In splenectomy, the spleen was removed before angiotensin II infusion. In the angiotensin II AT1 receptor blockade, telmisartan was administered by gastric gavage (10 mg/kg/day during angiotensin II infusion. The heart and aorta were isolated for Western blot analysis and immunohistochemistry. Results: Angiotensin II infusion caused a significant reduction in the number of monocytes in the spleen through the AT1 receptor-activated monocyte chemoattractant protein-1. Comparison of angiotensin II infusion, splenectomy and telmisartan comparatively reduced the recruitment of macrophages into the heart. Associated with this change, transforming growth factor β1 expression and myofibroblast proliferation were inhibited, and Smad2/3 and collagen I/III were downregulated. Furthermore, interstitial/perivascular fibrosis was attenuated. These modifications occurred in coincidence with reduced blood pressure. At week 4, invasion of macrophages and myofibroblasts in the thoracic aorta was attenuated and expression of endothelial nitric oxide synthase was upregulated, along with a reduction in aortic fibrosis. Conclusions: These results suggest that macrophages when recruited into the heart and aorta from the spleen potentially contribute to angiotensin II-induced cardiac fibrosis and hypertension.

  15. Controlled release of sphingosine-1-phosphate agonist with gelatin hydrogels for macrophage recruitment.

    Science.gov (United States)

    Murakami, Masahiro; Saito, Takashi; Tabata, Yasuhiko

    2014-11-01

    The objective of this study is to design a drug delivery system (DDS) for the in vivo promotion of macrophage recruitment. As the drug, a water-insoluble agonist of sphingosine-1-phosphate type 1 receptor (SEW2871) was selected. SEW2871 (SEW) was water-solubilized by micelle formation with gelatin grafted by L-lactic acid oligomer. SEW micelles were mixed with gelatin, followed by dehydrothermal crosslinking of gelatin to obtain gelatin hydrogels incorporating SEW micelles. SEW was released from the hydrogels incorporating SEW micelles in vitro and in vivo. The water-solubilized SEW showed in vitro macrophage migration activity. When implanted into the back subcutis or the skin wound defect of mice, the hydrogel incorporating SEW micelles promoted macrophage migration toward the tissue around the implanted site to a significantly great extent compared with SEW-free hydrogel and that mixed with SEW micelles. The hydrogel is a promising DDS to enhance macrophage recruitment in vivo. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  16. Progranulin Plays a Central Role in Host Defense during Sepsis by Promoting Macrophage Recruitment.

    Science.gov (United States)

    Song, Zhixin; Zhang, Xuemei; Zhang, Liping; Xu, Fang; Tao, Xintong; Zhang, Hua; Lin, Xue; Kang, Lihua; Xiang, Yu; Lai, Xaiofei; Zhang, Qun; Huang, Kun; Dai, Yubing; Yin, Yibing; Cao, Ju

    2016-11-15

    Progranulin, a widely expressed protein, has multiple physiological functions. The functional role of progranulin in the host response to sepsis remains unknown. To assess the role of progranulin in the host response to sepsis. Effects of progranulin on host response to sepsis were determined. Progranulin concentrations were significantly elevated in adult (n = 74) and pediatric (n = 26) patients with sepsis relative to corresponding healthy adult (n = 36) and pediatric (n = 17) control subjects, respectively. By using a low-lethality model of nonsevere sepsis, we observed that progranulin deficiency not only increased mortality but also decreased bacterial clearance during sepsis. The decreased host defense to sepsis in progranulin-deficient mice was associated with reduced macrophage recruitment, with correspondingly impaired chemokine CC receptor ligand 2 (CCL2) production in peritoneal lavages during the early phase of sepsis. Progranulin derived from hematopoietic cells contributed to host defense in sepsis. Therapeutic administration of recombinant progranulin not only rescued impaired host defense in progranulin-deficient mice after nonsevere sepsis but also protected wild-type mice against a high-lethality model of severe sepsis. Progranulin-mediated protection against sepsis was closely linked to improved peritoneal macrophage recruitment. In addition, CCL2 treatment of progranulin-deficient mice improved survival and decreased peritoneal bacterial loads during sepsis, at least in part through promotion of peritoneal macrophage recruitment. This proof-of-concept study supports a central role of progranulin-dependent macrophage recruitment in host defense to sepsis, opening new opportunities to host-directed therapeutic strategy that manipulate host immune response in the treatment of sepsis.

  17. Notch signaling mediates granulocyte-macrophage colony-stimulating factor priming-induced transendothelial migration of human eosinophils.

    Science.gov (United States)

    Liu, L Y; Wang, H; Xenakis, J J; Spencer, L A

    2015-07-01

    Priming with cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances eosinophil migration and exacerbates the excessive accumulation of eosinophils within the bronchial mucosa of asthmatics. However, mechanisms that drive GM-CSF priming are incompletely understood. Notch signaling is an evolutionarily conserved pathway that regulates cellular processes, including migration, by integrating exogenous and cell-intrinsic cues. This study investigates the hypothesis that the priming-induced enhanced migration of human eosinophils requires the Notch signaling pathway. Using pan Notch inhibitors and newly developed human antibodies that specifically neutralize Notch receptor 1 activation, we investigated a role for Notch signaling in GM-CSF-primed transmigration of human blood eosinophils in vitro and in the airway accumulation of mouse eosinophils in vivo. Notch receptor 1 was constitutively active in freshly isolated human blood eosinophils, and inhibition of Notch signaling or specific blockade of Notch receptor 1 activation during GM-CSF priming impaired priming-enhanced eosinophil transendothelial migration in vitro. Inclusion of Notch signaling inhibitors during priming was associated with diminished ERK phosphorylation, and ERK-MAPK activation was required for GM-CSF priming-induced transmigration. In vivo in mice, eosinophil accumulation within allergic airways was impaired following systemic treatment with Notch inhibitor, or adoptive transfer of eosinophils treated ex vivo with Notch inhibitor. These data identify Notch signaling as an intrinsic pathway central to GM-CSF priming-induced eosinophil tissue migration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Herpes Simplex Virus Type 1 Infects Enteric Neurons and Triggers Gut Dysfunction via Macrophage Recruitment.

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    Brun, Paola; Qesari, Marsela; Marconi, Peggy C; Kotsafti, Andromachi; Porzionato, Andrea; Macchi, Veronica; Schwendener, Reto A; Scarpa, Marco; Giron, Maria C; Palù, Giorgio; Calistri, Arianna; Castagliuolo, Ignazio

    2018-01-01

    Herpes Simplex Virus type 1 (HSV-1), a neurotropic pathogen widespread in human population, infects the enteric nervous system (ENS) in humans and rodents and causes intestinal neuromuscular dysfunction in rats. Although infiltration of inflammatory cells in the myenteric plexus and neurodegeneration of enteric nerves are common features of patients suffering from functional intestinal disorders, the proof of a pathogenic link with HSV-1 is still unsettled mainly because the underlying mechanisms are largely unknown. In this study we demonstrated that following intragastrical administration HSV-1 infects neurons within the myenteric plexus resulting in functional and structural alterations of the ENS. By infecting mice with HSV-1 replication-defective strain we revealed that gastrointestinal neuromuscular anomalies were however independent of viral replication. Indeed, enteric neurons exposed to UV-inactivated HSV-1 produced monocyte chemoattractant protein-1 (MCP-1/CCL2) to recruit activated macrophages in the longitudinal muscle myenteric plexus. Infiltrating macrophages produced reactive oxygen and nitrogen species and directly harmed enteric neurons resulting in gastrointestinal dysmotility. In HSV-1 infected mice intestinal neuromuscular dysfunctions were ameliorated by in vivo administration of (i) liposomes containing dichloromethylene bisphosphonic acid (clodronate) to deplete tissue macrophages, (ii) CCR2 chemokine receptor antagonist RS504393 to block the CCL2/CCR2 pathway, (iii) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and AR-C 102222 to quench production of nitrogen reactive species produced via iNOS. Overall these data demonstrate that HSV-1 infection makes enteric neurons recruit macrophages via production of a specific chemoattractant factor. The resulting inflammatory reaction is mandatory for intestinal dysmotility. These findings provide insights into the neuro-immune communication that occurs in the ENS following HSV-1 infection

  19. Herpes Simplex Virus Type 1 Infects Enteric Neurons and Triggers Gut Dysfunction via Macrophage Recruitment

    Directory of Open Access Journals (Sweden)

    Paola Brun

    2018-03-01

    Full Text Available Herpes Simplex Virus type 1 (HSV-1, a neurotropic pathogen widespread in human population, infects the enteric nervous system (ENS in humans and rodents and causes intestinal neuromuscular dysfunction in rats. Although infiltration of inflammatory cells in the myenteric plexus and neurodegeneration of enteric nerves are common features of patients suffering from functional intestinal disorders, the proof of a pathogenic link with HSV-1 is still unsettled mainly because the underlying mechanisms are largely unknown. In this study we demonstrated that following intragastrical administration HSV-1 infects neurons within the myenteric plexus resulting in functional and structural alterations of the ENS. By infecting mice with HSV-1 replication-defective strain we revealed that gastrointestinal neuromuscular anomalies were however independent of viral replication. Indeed, enteric neurons exposed to UV-inactivated HSV-1 produced monocyte chemoattractant protein-1 (MCP-1/CCL2 to recruit activated macrophages in the longitudinal muscle myenteric plexus. Infiltrating macrophages produced reactive oxygen and nitrogen species and directly harmed enteric neurons resulting in gastrointestinal dysmotility. In HSV-1 infected mice intestinal neuromuscular dysfunctions were ameliorated by in vivo administration of (i liposomes containing dichloromethylene bisphosphonic acid (clodronate to deplete tissue macrophages, (ii CCR2 chemokine receptor antagonist RS504393 to block the CCL2/CCR2 pathway, (iii Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME and AR-C 102222 to quench production of nitrogen reactive species produced via iNOS. Overall these data demonstrate that HSV-1 infection makes enteric neurons recruit macrophages via production of a specific chemoattractant factor. The resulting inflammatory reaction is mandatory for intestinal dysmotility. These findings provide insights into the neuro-immune communication that occurs in the ENS following HSV-1

  20. Promoting Recruitment using Information Management Efficiently (PRIME): a stepped-wedge, cluster randomised trial of a complex recruitment intervention embedded within the REstart or Stop Antithrombotics Randomised Trial.

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    Maxwell, Amy E; Parker, Richard A; Drever, Jonathan; Rudd, Anthony; Dennis, Martin S; Weir, Christopher J; Al-Shahi Salman, Rustam

    2017-12-28

    Few interventions are proven to increase recruitment in clinical trials. Recruitment to RESTART, a randomised controlled trial of secondary prevention after stroke due to intracerebral haemorrhage, has been slower than expected. Therefore, we sought to investigate an intervention to boost recruitment to RESTART. We conducted a stepped-wedge, cluster randomised trial of a complex intervention to increase recruitment, embedded within the RESTART trial. The primary objective was to investigate if the PRIME complex intervention (a recruitment co-ordinator who conducts a recruitment review, provides access to bespoke stroke audit data exports, and conducts a follow-up review after 6 months) increases the recruitment rate to RESTART. We included 72 hospital sites located in England, Wales, or Scotland that were active in RESTART in June 2015. All sites began in the control state and were allocated using block randomisation stratified by hospital location (Scotland versus England/Wales) to start the complex intervention in one of 12 different months. The primary outcome was the number of patients randomised into RESTART per month per site. We quantified the effect of the complex intervention on the primary outcome using a negative binomial, mixed model adjusting for site, December/January months, site location, and background time trends in recruitment rate. We recruited and randomised 72 sites and recorded their monthly recruitment to RESTART over 24 months (March 2015 to February 2017 inclusive), providing 1728 site-months of observations for the primary analysis. The adjusted rate ratio for the number of patients randomised per month after allocation to the PRIME complex intervention versus control time before allocation to the PRIME complex intervention was 1.06 (95% confidence interval 0.55 to 2.03, p = 0.87). Although two thirds of respondents to the 6-month follow-up questionnaire agreed that the audit reports were useful, only six patients were reported to

  1. Hydrogen Sulfide Recruits Macrophage Migration by Integrin β1-Src-FAK/Pyk2-Rac Pathway in Myocardial Infarction

    Science.gov (United States)

    Miao, Lei; Xin, Xiaoming; Xin, Hong; Shen, Xiaoyan; Zhu, Yi-Zhun

    2016-03-01

    Myocardial infarction (MI) triggers an inflammatory reaction, in which macrophages are of key importance for tissue repairing. Infiltration and/or migration of macrophages into the infarct area early after MI is critical for infarct healing, vascularization, and cardiac function. Hydrogen sulfide (H2S) has been demonstrated to possess cardioprotective effects post MI and during the progress of cardiac remodeling. However, the specific molecular and cellular mechanisms involved in macrophage recruitment by H2S remain to be identified. In this study, the NaHS (exogenous sources of H2S) treatment exerted an increased infiltration of macrophages into the infarcted myocardium at early stage of MI cardiac tissues in both wild type (WT) and cystathionine-γ-lyase-knockout (CSE-KO) mice. And NaHS accelerated the migration of macrophage cells in vitro. While, the inhibitors not only significantly diminished the migratory ability in response to NaHS, but also blocked the activation of phospho-Src, -Pyk2, -FAK397, and -FAK925. Furthermore, NaHS induced the internalization of integrin β1 on macrophage surface, but, integrin β1 silencing inhibited macrophage migration and Src signaling activation. These results indicate that H2S may have the potential as an anti-infarct of MI by governing macrophage migration, which was achieved by accelerating internalization of integrin β1 and activating downstream Src-FAK/Pyk2-Rac pathway.

  2. IL33 Promotes Colon Cancer Cell Stemness via JNK Activation and Macrophage Recruitment

    Science.gov (United States)

    Fang, Min; Li, Yongkui; Huang, Kai; Qi, Shanshan; Zhang, Jian; Zgodzinski, Witold; Majewski, Marek; Wallner, Grzegorz; Gozdz, Stanislaw; Macek, Pawel; Kowalik, Artur; Pasiarski, Marcin; Grywalska, Ewelina; Vatan, Linda; Nagarsheth, Nisha; Li, Wei; Zhao, Lili; Kryczek, Ilona; Wang, Guobin; Wang, Zheng; Zou, Weiping; Wang, Lin

    2018-01-01

    The expression and biological role of IL33 in colon cancer is poorly understood. In this study, we show that IL33 is expressed by vascular endothelial cells and tumor cells in the human colon cancer microenvironment. Administration of human IL33 and overexpression of murine IL33 enhanced human and murine colon cancer cell growth in vivo, respectively. IL33 stimulated cell sphere formation and prevented chemotherapy-induced tumor apoptosis. Mechanistically, IL33 activated core stem cell genes NANOG, NOTCH3, and OCT3/4 via the ST2 signaling pathway, and induced phosphorylation of c-Jun N terminal kinase (JNK) activation and enhanced binding of c-Jun to the promoters of the core stem cell genes. Moreover, IL33 recruited macrophages into the cancer microenvironment and stimulated them to produce prostaglandin E2, which supported colon cancer stemness and tumor growth. Clinically, tumor IL33 expression associated with poor survival in patients with metastatic colon cancer. Thus, IL33 dually targets tumor cells and macrophages and endows stem-like qualities to colon cancer cells to promote carcinogenesis. Collectively, our work reveals an immune-associated mechanism that extrinsically confers cancer cell stemness properties. Targeting the IL33 signaling pathway may offer an opportunity to treat patients with metastatic cancer. PMID:28249897

  3. A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment.

    Science.gov (United States)

    Sierro, Frederic; Evrard, Maximilien; Rizzetto, Simone; Melino, Michelle; Mitchell, Andrew J; Florido, Manuela; Beattie, Lynette; Walters, Shaun B; Tay, Szun Szun; Lu, Bo; Holz, Lauren E; Roediger, Ben; Wong, Yik Chun; Warren, Alessandra; Ritchie, William; McGuffog, Claire; Weninger, Wolfgang; Le Couteur, David G; Ginhoux, Florent; Britton, Warwick J; Heath, William R; Saunders, Bernadette M; McCaughan, Geoffrey W; Luciani, Fabio; MacDonald, Kelli P A; Ng, Lai Guan; Bowen, David G; Bertolino, Patrick

    2017-08-15

    The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Cardiosphere-Derived Cells Facilitate Heart Repair by Modulating M1/M2 Macrophage Polarization and Neutrophil Recruitment.

    Directory of Open Access Journals (Sweden)

    Al Shaimaa Hasan

    Full Text Available Cardiosphere-derived cells (CDCs, one of the promising stem cell sources for myocardial repair, have been tested in clinical trials and resulted in beneficial effects; however, the relevant mechanisms are not fully understood. In this study, we examined the hypothesis that CDCs favor heart repair by switching the macrophages from a pro-inflammatory phenotype (M1 into a regulatory anti-inflammatory phenotype (M2. Macrophages from mice were cultured with CDCs-conditioned medium or with fibroblasts-conditioned medium as a control. Immunostaining showed that CDCs-conditioned medium significantly enhanced the expression of CD206 (a marker for M2 macrophages, but decreased the expression of CD86 (a marker for M1 macrophages 3 days after culture. For animal studies, we used an acute myocardial infarction model of mice. We injected CDCs, fibroblasts, or saline only into the border zone of infarction. Then we collected the heart tissues for histological analysis 5 and 14 days after treatment. Compared with control animals, CDCs treatment significantly decreased M1 macrophages and neutrophils but increased M2 macrophages in the infarcted heart. Furthermore, CDCs-treated mice had reduced infarct size and fewer apoptotic cells compared to the controls. Our data suggest that CDCs facilitate heart repair by modulating M1/M2 macrophage polarization and neutrophil recruitment, which may provide a new insight into the mechanisms of stem cell-based myocardial repair.

  5. Cardiosphere-Derived Cells Facilitate Heart Repair by Modulating M1/M2 Macrophage Polarization and Neutrophil Recruitment

    Science.gov (United States)

    Hasan, Al Shaimaa; Luo, Lan; Yan, Chen; Zhang, Tian-Xia; Urata, Yoshishige; Goto, Shinji; Mangoura, Safwat A.; Abdel-Raheem, Mahmoud H.; Zhang, Shouhua; Li, Tao-Sheng

    2016-01-01

    Cardiosphere-derived cells (CDCs), one of the promising stem cell sources for myocardial repair, have been tested in clinical trials and resulted in beneficial effects; however, the relevant mechanisms are not fully understood. In this study, we examined the hypothesis that CDCs favor heart repair by switching the macrophages from a pro-inflammatory phenotype (M1) into a regulatory anti-inflammatory phenotype (M2). Macrophages from mice were cultured with CDCs-conditioned medium or with fibroblasts-conditioned medium as a control. Immunostaining showed that CDCs-conditioned medium significantly enhanced the expression of CD206 (a marker for M2 macrophages), but decreased the expression of CD86 (a marker for M1 macrophages) 3 days after culture. For animal studies, we used an acute myocardial infarction model of mice. We injected CDCs, fibroblasts, or saline only into the border zone of infarction. Then we collected the heart tissues for histological analysis 5 and 14 days after treatment. Compared with control animals, CDCs treatment significantly decreased M1 macrophages and neutrophils but increased M2 macrophages in the infarcted heart. Furthermore, CDCs-treated mice had reduced infarct size and fewer apoptotic cells compared to the controls. Our data suggest that CDCs facilitate heart repair by modulating M1/M2 macrophage polarization and neutrophil recruitment, which may provide a new insight into the mechanisms of stem cell-based myocardial repair. PMID:27764217

  6. Understanding delayed T-cell priming, lung recruitment, and airway luminal T-cell responses in host defense against pulmonary tuberculosis.

    Science.gov (United States)

    Shaler, Christopher R; Horvath, Carly; Lai, Rocky; Xing, Zhou

    2012-01-01

    Mycobacterium tuberculosis (M.tb), the causative bacterium of pulmonary tuberculosis (TB), is a serious global health concern. Central to M.tb effective immune avoidance is its ability to modulate the early innate inflammatory response and prevent the establishment of adaptive T-cell immunity for nearly three weeks. When compared with other intracellular bacterial lung pathogens, such as Legionella pneumophila, or even closely related mycobacterial species such as M. smegmatis, this delay is astonishing. Customarily, the alveolar macrophage (AM) acts as a sentinel, detecting and alerting surrounding cells to the presence of an invader. However, in the case of M.tb, this may be impaired, thus delaying the recruitment of antigen-presenting cells (APCs) to the lung. Upon uptake by APC populations, M.tb is able to subvert and delay the processing of antigen, MHC class II loading, and the priming of effector T cell populations. This delay ultimately results in the deferred recruitment of effector T cells to not only the lung interstitium but also the airway lumen. Therefore, it is of upmost importance to dissect the mechanisms that contribute to the delayed onset of immune responses following M.tb infection. Such knowledge will help design the most effective vaccination strategies against pulmonary TB.

  7. Human macrophages primed with angiogenic factors show dynamic plasticity, irrespective of extracellular matrix components

    NARCIS (Netherlands)

    Ploeger, Diana T. A.; van Putten, Sander M.; Koerts, Jasper A.; van Luyn, Marja J. A.; Harmsen, Martin C.

    Macrophages are important in inflammation as well as in tissue repair processes. They can be activated by various stimuli and classified into two major groups: M1 (classically activated) or M2 (alternatively activated). Inflammation, angiogenesis and matrix remodeling play a major role in tissue

  8. Interaction with extracellular matrix proteins influences Lsh/Ity/Bcg (candidate Nramp) gene regulation of macrophage priming/activation for tumour necrosis factor-alpha and nitrite release.

    Science.gov (United States)

    Formica, S; Roach, T I; Blackwell, J M

    1994-05-01

    The murine resistance gene Lsh/Ity/Bcg regulates activation of macrophages for tumour necrosis factor-alpha (TNF-alpha)-dependent production of nitric oxide mediating antimicrobial activity against Leishmania, Salmonella and Mycobacterium. As Lsh is differentially expressed in macrophages from different tissue sites, experiments were performed to determine whether interaction with extracellular matrix (ECM) proteins would influence the macrophage TNF-alpha response. Plating of bone marrow-derived macrophages onto purified fibrinogen or fibronectin-rich L929 cell-derived matrices, but not onto mannan, was itself sufficient to stimulate TNF-alpha release, with significantly higher levels released from congenic B10.L-Lshr compared to C57BL/10ScSn (Lshs) macrophages. Only macrophages plated onto fibrinogen also released measurable levels of nitrites, again higher in Lshr compared to Lshs macrophages. Addition of interferon-gamma (IFN-gamma), but not bacterial lipopolysaccharide or mycobacterial lipoarabinomannan, as a second signal enhanced the TNF-alpha and nitrite responses of macrophages plated onto fibrinogen, particularly in the Lshr macrophages. Interaction with fibrinogen and fibronectin also primed macrophages for an enhanced TNF-alpha response to leishmanial parasites, but this was only translated into enhanced nitrite responses in the presence of IFN-gamma. In these experiments, Lshr macrophages remained superior in their TNF-alpha responses throughout, but to a degree which reflected the magnitude of the difference observed on ECM alone. Hence, the specificity for the enhanced TNF-alpha responses of Lshr macrophages lay in their interaction with fibrinogen and fibronectin ECM, while a differential nitrite response was only observed with fibrinogen and/or IFN-gamma. The results are discussed in relation to the possible function of the recently cloned candidate gene Nramp, which has structural identity to eukaryote transporters and an N-terminal cytoplasmic

  9. Nicaraven reduces cancer metastasis to irradiated lungs by decreasing CCL8 and macrophage recruitment.

    Science.gov (United States)

    Yan, Chen; Luo, Lan; Urata, Yoshishige; Goto, Shinji; Li, Tao-Sheng

    2018-04-01

    Radiotherapy for cancer patients damages normal tissues, thereby inducing an inflammatory response and promoting cancer metastasis. We investigated whether nicaraven, a compound with radioprotective and anti-inflammatory properties, could attenuate radiation-induced cancer metastasis to the lungs of mice. Nicaraven and amifostine, another commercial radioprotective agent, had limited effects on both the radiosensitivity of Lewis lung carcinoma cells in vitro and radiation-induced tumor growth inhibition in vivo. Using experimental and spontaneous metastasis models, we confirmed that thorax irradiation with 5 Gy X-rays dramatically increased the number of tumors in the lungs. Interestingly, the number of tumors in the lungs was significantly reduced by administering nicaraven but not by administering amifostine daily after radiation exposure. Furthermore, nicaraven administration effectively inhibited CCL8 expression and macrophage recruitment in the lungs 1 day after thorax irradiation. Our data suggest that nicaraven attenuates radiation-induced lung metastasis, likely by regulating the inflammatory response after radiation exposure. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. The LPS-induced neutrophil recruitment into rat air pouches is mediated by TNFα: likely macrophage origin

    Directory of Open Access Journals (Sweden)

    C-D. Arreto

    1997-01-01

    Full Text Available The role of resident cells during the lipopolysaccharide (LPS-induced neutrophil recruitment into rat air pouches was investigated. In this model, LPS (Escherichia coli, O55: B5 strain; 2–2000 ng induced a dose– and time-dependent neutrophil recruitment accompanied by the generation of a tumour necrosis factor-α (TNFα-like activity. Dexamethasone (0.05–5 mug and cycloheximide (6 ng, injected 2 h before LPS into the pouches, inhibited the neutrophil recruitment and the generation of the TNFα-like activity, while the H1-receptor antagonist mepyramine (1 and 4 mg/kg, i.p., 0.5 h before LPS and the PAF-receptor antagonist WEB 2170 (0.05 and 1 mg/kg, i.p., 0.5 h before LPS had no effect. Purified alveolar macrophages (AM were used to replenish the pouches of cycloheximide-treated recipient rats. AM provided by PBS-treated animals led to the recovery of the LPS-induced neutrophil recruitment and of the TNFα-like formation contrasting with those from cycloheximide-treated animals (1 mg/kg, i.p.. When delivered in situ, liposome-encapsulated clodronate, a macrophage depletor, significantly impaired both the LPSinduced neutrophil recruitment and the TNFα-like activity. An anti-murine TNFα polyclonal antibody (0.5 h before LPS was also effective. These results emphasize the pivotal role of macrophages for LPS-induced neutrophil recruitment via the formation of TNFα.

  11. The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ

    Science.gov (United States)

    Appelberg, Rui; Moreira, Diana; Barreira-Silva, Palmira; Borges, Margarida; Silva, Letícia; Dinis-Oliveira, Ricardo Jorge; Resende, Mariana; Correia-Neves, Margarida; Jordan, Michael B; Ferreira, Nuno C; Abrunhosa, Antero J; Silvestre, Ricardo

    2015-01-01

    Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-γ (IFN-γ). Mycobacterium avium-infected mice lacking IFN-γ signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine-18-fluorodeoxyglucose (FDG). To assess the role of macrophages in glucose uptake we infected mice with a selective impairment of IFN-γ signalling in the macrophage lineage (MIIG mice). Although only a partial reduction of the granulomatous areas was observed in infected MIIG mice, the insensitivity of macrophages to IFN-γ reduced the accumulation of FDG. In vivo, ex vivo and in vitro assays showed that macrophage activated by IFN-γ displayed increased rates of glucose uptake and in vitro studies showed also that they had increased lactate production and increased expression of key glycolytic enzymes. Overall, our results show that the activation of macrophages by IFN-γ is responsible for the Warburg effect observed in organs infected with M. avium. PMID:25807843

  12. Hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineage.

    Science.gov (United States)

    Frid, Maria G; Brunetti, Jacqueline A; Burke, Danielle L; Carpenter, Todd C; Davie, Neil J; Reeves, John T; Roedersheimer, Mark T; van Rooijen, Nico; Stenmark, Kurt R

    2006-02-01

    Vascular remodeling in chronic hypoxic pulmonary hypertension includes marked fibroproliferative changes in the pulmonary artery (PA) adventitia. Although resident PA fibroblasts have long been considered the primary contributors to these processes, we tested the hypothesis that hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineage, termed fibrocytes. Using two neonatal animal models (rats and calves) of chronic hypoxic pulmonary hypertension, we demonstrated a dramatic perivascular accumulation of mononuclear cells of a monocyte/macrophage lineage (expressing CD45, CD11b, CD14, CD68, ED1, ED2). Many of these cells produced type I collagen, expressed alpha-smooth muscle actin, and proliferated, thus exhibiting mesenchymal cell characteristics attributed to fibrocytes. The blood-borne origin of these cells was confirmed in experiments wherein circulating monocytes/macrophages of chronically hypoxic rats were in vivo-labeled with DiI fluorochrome via liposome delivery and subsequently identified in the remodeled pulmonary, but not systemic, arterial adventitia. The DiI-labeled cells that appeared in the vessel wall expressed monocyte/macrophage markers and procollagen. Selective depletion of this monocytic cell population, using either clodronate-liposomes or gadolinium chloride, prevented pulmonary adventitial remodeling (ie, production of collagen, fibronectin, and tenascin-C and accumulation of myofibroblasts). We conclude that circulating mesenchymal precursors of a monocyte/macrophage lineage, including fibrocytes, are essential contributors to hypoxia-induced pulmonary vascular remodeling.

  13. Activated prostaglandin D2 receptors on macrophages enhance neutrophil recruitment into the lung

    Science.gov (United States)

    Jandl, Katharina; Stacher, Elvira; Bálint, Zoltán; Sturm, Eva Maria; Maric, Jovana; Peinhaupt, Miriam; Luschnig, Petra; Aringer, Ida; Fauland, Alexander; Konya, Viktoria; Dahlen, Sven-Erik; Wheelock, Craig E.; Kratky, Dagmar; Olschewski, Andrea; Marsche, Gunther; Schuligoi, Rufina; Heinemann, Akos

    2016-01-01

    Background Prostaglandin (PG) D2 is an early-phase mediator in inflammation, but its action and the roles of the 2 D-type prostanoid receptors (DPs) DP1 and DP2 (also called chemoattractant receptor–homologous molecule expressed on TH2 cells) in regulating macrophages have not been elucidated to date. Objective We investigated the role of PGD2 receptors on primary human macrophages, as well as primary murine lung macrophages, and their ability to influence neutrophil action in vitro and in vivo. Methods In vitro studies, including migration, Ca2+ flux, and cytokine secretion, were conducted with primary human monocyte-derived macrophages and neutrophils and freshly isolated murine alveolar and pulmonary interstitial macrophages. In vivo pulmonary inflammation was assessed in male BALB/c mice. Results Activation of DP1, DP2, or both receptors on human macrophages induced strong intracellular Ca2+ flux, cytokine release, and migration of macrophages. In a murine model of LPS-induced pulmonary inflammation, activation of each PGD2 receptor resulted in aggravated airway neutrophilia, tissue myeloperoxidase activity, cytokine contents, and decreased lung compliance. Selective depletion of alveolar macrophages abolished the PGD2-enhanced inflammatory response. Activation of PGD2 receptors on human macrophages enhanced the migratory capacity and prolonged the survival of neutrophils in vitro. In human lung tissue specimens both DP1 and DP2 receptors were located on alveolar macrophages along with hematopoietic PGD synthase, the rate-limiting enzyme of PGD2 synthesis. Conclusion For the first time, our results show that PGD2 markedly augments disease activity through its ability to enhance the proinflammatory actions of macrophages and subsequent neutrophil activation. PMID:26792210

  14. Macrophage colony-stimulating factor receptor marks and regulates a fetal myeloid-primed B-cell progenitor in mice.

    Science.gov (United States)

    Zriwil, Alya; Böiers, Charlotta; Wittmann, Lilian; Green, Joanna C A; Woll, Petter S; Jacobsen, Sten Eirik W; Sitnicka, Ewa

    2016-07-14

    Although it is well established that unique B-cell lineages develop through distinct regulatory mechanisms during embryonic development, much less is understood about the differences between embryonic and adult B-cell progenitor cells, likely to underpin the genetics and biology of infant and childhood PreB acute lymphoblastic leukemia (PreB-ALL), initiated by distinct leukemia-initiating translocations during embryonic development. Herein, we establish that a distinct subset of the earliest CD19(+) B-cell progenitors emerging in the E13.5 mouse fetal liver express the colony-stimulating factor-1 receptor (CSF1R), previously thought to be expressed, and play a lineage-restricted role in development of myeloid lineages, and macrophages in particular. These early embryonic CSF1R(+)CD19(+) ProB cells also express multiple other myeloid genes and, in line with this, possess residual myeloid as well as B-cell, but not T-cell lineage potential. Notably, these CSF1R(+) myeloid-primed ProB cells are uniquely present in a narrow window of embryonic fetal liver hematopoiesis and do not persist in adult bone marrow. Moreover, analysis of CSF1R-deficient mice establishes a distinct role of CSF1R in fetal B-lymphopoiesis. CSF1R(+) myeloid-primed embryonic ProB cells are relevant for infant and childhood PreB-ALLs, which frequently have a bi-phenotypic B-myeloid phenotype, and in which CSF1R-rearrangements have recently been reported. © 2016 by The American Society of Hematology.

  15. Obesity exacerbates colitis-associated cancer via IL-6-regulated macrophage polarisation and CCL-20/CCR-6-mediated lymphocyte recruitment.

    Science.gov (United States)

    Wunderlich, Claudia M; Ackermann, P Justus; Ostermann, Anna Lena; Adams-Quack, Petra; Vogt, Merly C; Tran, My-Ly; Nikolajev, Alexei; Waisman, Ari; Garbers, Christoph; Theurich, Sebastian; Mauer, Jan; Hövelmeyer, Nadine; Wunderlich, F Thomas

    2018-04-25

    Colorectal cancer (CRC) is one of the most lethal cancers worldwide in which the vast majority of cases exhibit little genetic risk but are associated with a sedentary lifestyle and obesity. Although the mechanisms underlying CRC and colitis-associated colorectal cancer (CAC) remain unclear, we hypothesised that obesity-induced inflammation predisposes to CAC development. Here, we show that diet-induced obesity accelerates chemically-induced CAC in mice via increased inflammation and immune cell recruitment. Obesity-induced interleukin-6 (IL-6) shifts macrophage polarisation towards tumour-promoting macrophages that produce the chemokine CC-chemokine-ligand-20 (CCL-20) in the CAC microenvironment. CCL-20 promotes CAC progression by recruiting CC-chemokine-receptor-6 (CCR-6)-expressing B cells and γδ T cells via chemotaxis. Compromised cell recruitment as well as inhibition of B and γδ T cells protects against CAC progression. Collectively, our data reveal a function for IL-6 in the CAC microenvironment via lymphocyte recruitment through the CCL-20/CCR-6 axis, thereby implicating a potential therapeutic intervention for human patients.

  16. Placental Growth Factor Contributes to Liver Inflammation, Angiogenesis, Fibrosis in Mice by Promoting Hepatic Macrophage Recruitment and Activation

    Directory of Open Access Journals (Sweden)

    Xi Li

    2017-07-01

    Full Text Available Placental growth factor (PlGF, a member of the vascular endothelial growth factor (VEGF family, mediates wound healing and inflammatory responses, exerting an effect on liver fibrosis and angiogenesis; however, the precise mechanism remains unclear. The aims of this study are to identify the role of PlGF in liver inflammation and fibrosis induced by bile duct ligation (BDL in mice and to reveal the underlying molecular mechanism. PlGF small interfering RNA (siRNA or non-targeting control siRNA was injected by tail vein starting 2 days after BDL. Liver inflammation, fibrosis, angiogenesis, macrophage infiltration, and hepatic stellate cells (HSCs activation were examined. Our results showed that PlGF was highly expressed in fibrotic livers and mainly distributed in activated HSCs and macrophages. Furthermore, PlGF silencing strongly reduced the severity of liver inflammation and fibrosis, and inhibited the activation of HSCs. Remarkably, PlGF silencing also attenuated BDL-induced hepatic angiogenesis, as evidenced by attenuated liver endothelial cell markers CD31 and von Willebrand factor immunostaining and genes or protein expression. Interestingly, these pathological ameliorations by PlGF silencing were due to a marked reduction in the numbers of intrahepatic F4/80+, CD68+, and Ly6C+ cell populations, which were reflected by a lower expression of these macrophage marker molecules in fibrotic livers. In addition, knockdown of PlGF by siRNA inhibited macrophages activation and substantially suppressed the expression of pro-inflammatory cytokines and chemokines in fibrotic livers. Mechanistically, evaluation of cultured RAW 264.7 cells revealed that VEGF receptor 1 (VEGFR1 mainly involved in mediating the role of PlGF in macrophages recruitment and activation, since using VEGFR1 neutralizing antibody blocking PlGF/VEGFR1 signaling axis significantly inhibited macrophages migration and inflammatory responses. Together, these findings indicate

  17. Cells of the J774 macrophage cell line are primed for antibody-dependent cell-mediated cytotoxicity following exposure to γ-irradiation

    International Nuclear Information System (INIS)

    Duerst, R.; Werberig, K.

    1991-01-01

    Activation of macrophages (M phi) for host defense against tumor cells follows a sequence of priming events followed by an initiating stimulus that results in production and release of cytotoxic molecules that mediate target cell killing. The authors have developed a model to study specific macrophage cytotoxicity in vitro utilizing a cultured murine M phi cell line, J774. Specific cytotoxicity of cultured human gastrointestinal tumor cells is achieved in the presence of murine IgG2a monoclonal antibody (mAb) 17-1-A. The ability of these cells to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) is greatly enhanced following gamma-irradiation. ADCC can be demonstrated at mAb 17-1-A concentrations greater than or equal to 1 microgram/ml and effector/target cell ratios greater than or equal to 2. Exposure to doses greater than or equal to 10 Gy of gamma-irradiation increases ADCC threefold. Varying the duration from J774 M phi exposure to γ-irradiation until addition of antibody-coated target cells showed that the primed state for ADCC is stable for at least 8 days but approximately 24 hr is required for complete development of the primed state. mAb-dependent target cell death begins 8 hr after addition of mAb and labeled target cells to primed effector cells and is complete by 24 hr. Incubation of unirradiated J774 M phi effector cells with recombinant murine interferon-γ (rmIFN-γ) also results in enhanced ADCC, but the extent of target cell killing achieved is less than that following priming by γ-irradiation. Concomitant priming of γ-irradiated J774 M phi with rmIFN-γ increases the extent of ADCC. Further study of irradiated J774 cells may elucidate the molecular pathways utilized by M phi for achieving and maintaining the primed state for ADCC

  18. Macrophage recruitment, but not interleukin 1 beta activation, enhances noise-induced hearing damage.

    Science.gov (United States)

    Mizushima, Yu; Fujimoto, Chisato; Kashio, Akinori; Kondo, Kenji; Yamasoba, Tatsuya

    2017-11-18

    It has been suggested that macrophages or inflammatory monocytes participate in the pathology of noise-induced hearing loss (NIHL), but it is unclear how extensively these cells contribute to the development of temporary and/or permanent NIHL. To address this question, we used clodronate liposomes to deplete macrophages and monocytes. After clodronate liposome injection, mice were exposed to 4-kHz octave band noise at 121 dB for 4 h. Compared to vehicle-injected controls, clodronate-treated mice exhibited significantly reduced permanent threshold shifts at 4 and 8 kHz and significantly smaller outer hair cell losses in the lower-apical cochlear turn. Following noise exposure, the stria vascularis had significantly more cells expressing the macrophage-specific protein F4/80, and this effect was significantly suppressed by clodronate treatment. These F4/80-positive cells expressed interleukin 1 beta (IL-1β), which noise exposure activated. However, IL-1β deficient mice did not exhibit significant resistance to intense noise when compared to wild-type mice. These findings suggest that macrophages that enter the cochlea after noise exposure are involved in NIHL, whereas IL-1β inhibition does not reverse this cochlear damage. Therefore, macrophages may be a promising therapeutic target in human sensorineural hearing losses such as NIHL. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. DMPD: Signals and receptors involved in recruitment of inflammatory cells. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 7744810 Signals and receptors involved in recruitment of inflammatory cells. Ben-Ba...ow Signals and receptors involved in recruitment of inflammatory cells. PubmedID 7744810 Title Signals and receptors involved in recr...uitment of inflammatory cells. Authors Ben-Baruch A, Mic

  20. Porphyromonas gulae Activates Unprimed and Gamma Interferon-Primed Macrophages via the Pattern Recognition Receptors Toll-Like Receptor 2 (TLR2), TLR4, and NOD2

    Science.gov (United States)

    Holden, James A.; O'Brien-Simpson, Neil M.; Lenzo, Jason C.; Orth, Rebecca K. H.; Mansell, Ashley

    2017-01-01

    ABSTRACT Porphyromonas gulae is an anaerobic, Gram-negative coccobacillus that has been associated with periodontal disease in companion animals. The aims of this study were to analyze the ligation of pattern recognition receptors by P. gulae and the subsequent activation of macrophages. Exposure of HEK cells transfected with Toll-like receptors (TLRs) or NOD-like receptors to P. gulae resulted in the ligation of TLR2, TLR4, and NOD2. The effects of this engagement of receptors were investigated by measuring the synthesis of nitric oxide (NO), CD86 expression, and inflammatory cytokine production by wild-type, TLR2−/−, and TLR4−/− macrophages. The addition of P. gulae to unprimed and gamma interferon (IFN-γ)-primed (M1 phenotype) macrophages significantly increased the surface expression of CD86, but only M1 macrophages produced nitric oxide. P. gulae-induced expression of CD86 on unprimed macrophages was dependent on both TLR2 and TLR4, but CD86 expression and NO production in M1 macrophages were only TLR2 dependent. P. gulae induced an increase in secretion of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12p70, IL-13, tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1α (MIP-1α) by M1 macrophages compared to that by unprimed controls. Among these cytokines, secretion of IL-6 and TNF-α by M1 macrophages was dependent on either TLR2 or TLR4. Our data indicate that TLR2 and TLR4 are important for P. gulae activation of unprimed macrophages and that activation and effector functions induced in M1 macrophages by P. gulae are mainly dependent on TLR2. In conclusion, P. gulae induces a strong TLR2-dependent inflammatory M1 macrophage response which may be important in establishing the chronic inflammation associated with periodontal disease in companion animals. PMID:28630066

  1. Porphyromonas gulae Activates Unprimed and Gamma Interferon-Primed Macrophages via the Pattern Recognition Receptors Toll-Like Receptor 2 (TLR2), TLR4, and NOD2.

    Science.gov (United States)

    Holden, James A; O'Brien-Simpson, Neil M; Lenzo, Jason C; Orth, Rebecca K H; Mansell, Ashley; Reynolds, Eric C

    2017-09-01

    Porphyromonas gulae is an anaerobic, Gram-negative coccobacillus that has been associated with periodontal disease in companion animals. The aims of this study were to analyze the ligation of pattern recognition receptors by P. gulae and the subsequent activation of macrophages. Exposure of HEK cells transfected with Toll-like receptors (TLRs) or NOD-like receptors to P. gulae resulted in the ligation of TLR2, TLR4, and NOD2. The effects of this engagement of receptors were investigated by measuring the synthesis of nitric oxide (NO), CD86 expression, and inflammatory cytokine production by wild-type, TLR2 -/- , and TLR4 -/- macrophages. The addition of P. gulae to unprimed and gamma interferon (IFN-γ)-primed (M1 phenotype) macrophages significantly increased the surface expression of CD86, but only M1 macrophages produced nitric oxide. P. gulae- induced expression of CD86 on unprimed macrophages was dependent on both TLR2 and TLR4, but CD86 expression and NO production in M1 macrophages were only TLR2 dependent. P. gulae induced an increase in secretion of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12p70, IL-13, tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1α (MIP-1α) by M1 macrophages compared to that by unprimed controls. Among these cytokines, secretion of IL-6 and TNF-α by M1 macrophages was dependent on either TLR2 or TLR4. Our data indicate that TLR2 and TLR4 are important for P. gulae activation of unprimed macrophages and that activation and effector functions induced in M1 macrophages by P. gulae are mainly dependent on TLR2. In conclusion, P. gulae induces a strong TLR2-dependent inflammatory M1 macrophage response which may be important in establishing the chronic inflammation associated with periodontal disease in companion animals. Copyright © 2017 American Society for Microbiology.

  2. A matrix of cholesterol crystals, but not cholesterol alone, primes human monocytes/macrophages for excessive endotoxin-induced production of tumor necrosis factor-alpha. Role in atherosclerotic inflammation?

    DEFF Research Database (Denmark)

    Bendtzen, Klaus; Christensen, Ole; Nielsen, Claus Henrik

    2014-01-01

    When exposed to small amounts of bacterial endotoxin, matrices of cholesterol crystals, but not cholesterol itself, primed human monocytes/macrophages to a highly augmented (>10-fold) production of inflammatory tumor necrosis factor-α. Priming also sensitized the cells, as 10- to 100-fold lower...

  3. Pace of macrophage recruitment during different stages of soft tissue infection: Semi-quantitative evaluation by in vivo magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jin Seong; Sohn, Jin Young [University of Ulsan College of Medicine, Asan Medical Center, Laboratory for Molecular and Functional Imaging, Department of Radiology and Research Institute of Radiology, Seoul (Korea); Jung, Hyun-Don; Kim, Sang-Tae [University of Ulsan College of Medicine, Asan Institute for Life Sciences, Seoul (Korea); Lee, Kyoung Geun [Korea University College of Life Sciences and Biotechnology, Division of Biotechnology, Seoul (Korea); Kang, Hee Jung [Hallym University College of Medicine, Department of Laboratory Medicine, Anyang (Korea)

    2008-10-15

    We describe the pace of recruitment of iron-oxide-labeled macrophages to the site of different stages of infection by in vivo magnetic resonance (MR) imaging. Peritoneal macrophages were labeled with superparamagnetic iron oxide ex vivo and administered through the tail vein 6 (acute) or 48 (subacute) h after bacterial inoculation. The legs of the mice were imaged sequentially on a 4.7-T MR unit before and 3, 6, 12, 18, 24, 48 and 72 h after macrophage administration. The band-shaped lower signal intensity zone around the abscess on T2*-weighted GRE images became more obvious due to recruited macrophages up until 24 h after injection in the subacute and 48 h after injection in the acute group, indicating that the relative SI of the abscess wall decreased more rapidly and the pace of recruitment of macrophages was faster in the subacute than in the acute group. Chemokine antibody arrays of mouse sera detected increased concentration of granulocyte-colony-stimulating factor and tissue inhibitor of metalloproteinase-1 beginning at 12 h and increased interleukin-13 at 18 h. Monocyte chemoattractant protein-1 and macrophage-colony-stimulating factor began to increase at 96 h after infection. This difference in pace of recruitment may result from the release of chemokines. (orig.)

  4. Pace of macrophage recruitment during different stages of soft tissue infection: Semi-quantitative evaluation by in vivo magnetic resonance imaging

    International Nuclear Information System (INIS)

    Lee, Jin Seong; Sohn, Jin Young; Jung, Hyun-Don; Kim, Sang-Tae; Lee, Kyoung Geun; Kang, Hee Jung

    2008-01-01

    We describe the pace of recruitment of iron-oxide-labeled macrophages to the site of different stages of infection by in vivo magnetic resonance (MR) imaging. Peritoneal macrophages were labeled with superparamagnetic iron oxide ex vivo and administered through the tail vein 6 (acute) or 48 (subacute) h after bacterial inoculation. The legs of the mice were imaged sequentially on a 4.7-T MR unit before and 3, 6, 12, 18, 24, 48 and 72 h after macrophage administration. The band-shaped lower signal intensity zone around the abscess on T2*-weighted GRE images became more obvious due to recruited macrophages up until 24 h after injection in the subacute and 48 h after injection in the acute group, indicating that the relative SI of the abscess wall decreased more rapidly and the pace of recruitment of macrophages was faster in the subacute than in the acute group. Chemokine antibody arrays of mouse sera detected increased concentration of granulocyte-colony-stimulating factor and tissue inhibitor of metalloproteinase-1 beginning at 12 h and increased interleukin-13 at 18 h. Monocyte chemoattractant protein-1 and macrophage-colony-stimulating factor began to increase at 96 h after infection. This difference in pace of recruitment may result from the release of chemokines. (orig.)

  5. Interleukin-34 promotes tumor progression and metastatic process in osteosarcoma through induction of angiogenesis and macrophage recruitment.

    Science.gov (United States)

    Ségaliny, Aude I; Mohamadi, Amel; Dizier, Blandine; Lokajczyk, Anna; Brion, Régis; Lanel, Rachel; Amiaud, Jérôme; Charrier, Céline; Boisson-Vidal, Catherine; Heymann, Dominique

    2015-07-01

    Interleukin-34 (IL-34) was recently characterized as the M-CSF "twin" cytokine, regulating the proliferation/differentiation/survival of myeloid cells. The implication of M-CSF in oncology was initially suspected by the reduced metastatic dissemination in knock-out mice, due to angiogenesis impairment. Based on this observation, our work studied the involvement of IL-34 in the pathogenesis of osteosarcoma. The in vivo effects of IL-34 were assessed on tissue vasculature and macrophage infiltration in a murine preclinical model based on a paratibial inoculation of human osteosarcoma cells overexpressing or not IL-34 or M-CSF. In vitro investigations using endothelial cell precursors and mature HUVEC cells were performed to analyse the involvement of IL-34 in angiogenesis and myeloid cell adhesion. The data revealed that IL-34 overexpression was associated with the progression of osteosarcoma (tumor growth, lung metastases) and an increase of neo-angiogenesis. In vitro analyses demonstrated that IL-34 stimulated endothelial cell proliferation and vascular cord formation. Pre-treatment of endothelial cells by chondroitinases/heparinases reduced the formation of vascular tubes and abolished the associated cell signalling. In addition, IL-34 increased the in vivo recruitment of M2 tumor-associated macrophages into the tumor tissue. IL-34 increased in vitro monocyte/CD34(+) cell adhesion to activated HUVEC monolayers under physiological shear stress conditions. This work also demonstrates that IL-34 is expressed by osteosarcoma cells, is regulated by TNF-α, IL-1β, and contributes to osteosarcoma growth by increasing the neo-angiogenesis and the recruitment of M2 macrophages. By promoting new vessel formation and extravasation of immune cells, IL-34 may play a key role in tumor development and inflammatory diseases. © 2014 UICC.

  6. Fractalkine Signaling Regulates Macrophage Recruitment into the Cochlea and Promotes the Survival of Spiral Ganglion Neurons after Selective Hair Cell Lesion.

    Science.gov (United States)

    Kaur, Tejbeer; Zamani, Darius; Tong, Ling; Rubel, Edwin W; Ohlemiller, Kevin K; Hirose, Keiko; Warchol, Mark E

    2015-11-11

    Macrophages are recruited into the cochlea in response to injury caused by acoustic trauma or ototoxicity, but the nature of the interaction between macrophages and the sensory structures of the inner ear remains unclear. The present study examined the role of fractalkine signaling in regulating the injury-evoked behavior of macrophages following the selective ablation of cochlear hair cells. We used a novel transgenic mouse model in which the human diphtheria toxin receptor (huDTR) is selectively expressed under the control of Pou4f3, a hair cell-specific transcription factor. Administration of diphtheria toxin (DT) to these mice resulted in nearly complete ablation of cochlear hair cells, with no evident pathology among supporting cells, spiral ganglion neurons, or cells of the cochlear lateral wall. Hair cell death led to an increase in macrophages associated with the sensory epithelium of the cochlea. Their numbers peaked at 14 days after DT and then declined at later survival times. Increased macrophages were also observed within the spiral ganglion, but their numbers remained elevated for (at least) 56 d after DT. To investigate the role of fractalkine signaling in macrophage recruitment, we crossed huDTR mice to a mouse line that lacks expression of the fractalkine receptor (CX3CR1). Disruption of fractalkine signaling reduced macrophage recruitment into both the sensory epithelium and spiral ganglion and also resulted in diminished survival of spiral ganglion neurons after hair cell death. Our results suggest a fractalkine-mediated interaction between macrophages and the neurons of the cochlea. It is known that damage to the inner ear leads to recruitment of inflammatory cells (macrophages), but the chemical signals that initiate this recruitment and the functions of macrophages in the damaged ear are unclear. Here we show that fractalkine signaling regulates macrophage recruitment into the cochlea and also promotes the survival of cochlear afferents after

  7. DMPD: Viral immunity: cross-priming with the help of TLR3. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15886091 Viral immunity: cross-priming with the help of TLR3. Salio M, Cerundolo V.... Curr Biol. 2005 May 10;15(9):R336-9. (.png) (.svg) (.html) (.csml) Show Viral immunity: cross-priming with the help... of TLR3. PubmedID 15886091 Title Viral immunity: cross-priming with the help of TLR3. Authors Salio

  8. Thromboxane A{sub 2} receptor signaling promotes liver tissue repair after toxic injury through the enhancement of macrophage recruitment

    Energy Technology Data Exchange (ETDEWEB)

    Minamino, Tsutomu [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ito, Yoshiya [Departments of Surgery, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ohkubo, Hirotoki [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Surgery, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Hosono, Kanako; Suzuki, Tatsunori [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Sato, Takehito [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ae, Takako; Shibuya, Akitaka [Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Sakagami, Hiroyuki [Departments of Anatomy, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Narumiya, Shuh [Department of Pharmacology, Kyoto University School of Medicine, Kyoto, 606-8315 (Japan); Koizumi, Wasaburo [Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Majima, Masataka, E-mail: mmajima@med.kitasato-u.ac.jp [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan)

    2012-02-15

    It is thought that thromboxane A{sub 2} (TxA{sub 2}) contributes to the progression of inflammation during acute hepatic injury; however, it is still unknown whether TxA{sub 2} is involved in liver repair. The objective of the present study was to examine the role of TxA{sub 2} receptor (TP) signaling in liver injury and repair in response to toxic injury. Carbon tetrachloride (CCl{sub 4}) was used to induce liver injury in TP knockout (TP{sup −/−}) mice and wild-type (WT) mice. In WT mice, serum levels of alanine aminotransferase (ALT) and the size of the necrotic area peaked at 24 and 48 h, respectively, and then declined. In TP{sup −/−} mice, the changes in ALT levels were similar to WT mice, but liver regeneration was impaired as evidenced by remained elevated levels of hepatic necrosis and by delayed hepatocyte proliferation, which was associated with the reduced expression of growth factors including interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and hepatocyte growth factor (HGF). In TP{sup −/−} mice, the accumulation of hepatic CD11b{sup +}/F4/80{sup +} macrophages in injured livers was attenuated, and the hepatic expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor, the C―C chemokine receptor (CCR2), was reduced compared to WT. Additionally, the application of the TP receptor agonist, U-46619, enhanced the expression of MCP-1/CCL2 and CCR2 in peritoneal macrophages, which was associated with increased levels of IL-6, TNFα and HGF. These results suggested that TP receptor signaling facilitates liver recovery following CCl{sub 4}-induced hepatotoxicity by affecting the expression of hepatotrophic growth factors, and through the recruitment of macrophages mediated by MCP-1/CCL2-CCR2 expression. -- Highlights: ► TP enhances liver regeneration by CCl{sub 4}. ► TP accumulates macrophages. ► TP up-regulates MCP-1.

  9. Tumor-Associated Macrophages Recruit CCR6+ Regulatory T Cells and Promote the Development of Colorectal Cancer via Enhancing CCL20 Production in Mice

    Science.gov (United States)

    Li, Qun; Zhang, Weiwei; Ke, Fang; Leng, Qibin; Wang, Hong; Chen, Jinfei; Wang, Honglin

    2011-01-01

    Background Tumor-associated macrophages (TAMs) remodel the colorectal cancer (CRC) microenvironment. Yet, findings on the role of TAMs in CRC seem to be contradictory compared with other cancers. FoxP3+ regulatory T (Treg)-cells dominantly infiltrate CRC. However, the underlying molecular mechanism in which TAMs may contribute to the trafficking of Treg-cells to the tumor mass remains unknown. Methodology/Principal Findings CRC was either induced by N-methyl-N-nitrosourea (MNU) and H. pylori or established by subcutaneous injection of mouse colorectal tumor cell line (CMT93) in mice. CMT93 cells were co-cultured with primary macrophages in a transwell apparatus. Recruitment of FoxP3 green fluorescence protein positive (FoxP3GFP+) Treg-cells was assessed using the IVIS Imaging System or immunofluorescence staining. A role for macrophages in trafficking of Treg-cells and in the development of CRC was investigated in CD11b diphtheria toxin receptor (CD11b-DTR) transgenic C57BL/6J mice in which macrophages can be selectively depleted. Treg-cells remarkably infiltrated solid tumor, and predominantly expressed the homing chemokine receptor (CCR) 6 in the induced CRC model. Both CMT93 cancer cells and macrophages produced a large amount of CCL20, the sole ligand of CCR6 in vitro and in vivo. Injection of recombinant mouse CCL20 into tumor sites promoted its development with a marked recruitment of Treg-cells in the graft CRC model. Conditional macrophage ablation decreased CCL20 levels, blocked Treg-cell recruitment and inhibited tumor growth in CD11b-DTR mice grafted with CMT93. Conclusions/Significance TAMs recruit CCR6+ Treg-cells to tumor mass and promote its development via enhancing the production of CCL20 in a CRC mouse model. PMID:21559338

  10. Fibroblast growth factor receptor 1 activation in mammary tumor cells promotes macrophage recruitment in a CX3CL1-dependent manner.

    Directory of Open Access Journals (Sweden)

    Johanna R Reed

    Full Text Available Tumor formation is an extensive process requiring complex interactions that involve both tumor cell-intrinsic pathways and soluble mediators within the microenvironment. Tumor cells exploit the intrinsic functions of many soluble molecules, including chemokines and their receptors, to regulate pro-tumorigenic phenotypes that are required for growth and progression of the primary tumor. Previous studies have shown that activation of inducible FGFR1 (iFGFR1 in mammary epithelial cells resulted in increased proliferation, migration, and invasion in vitro and tumor formation in vivo. These studies also demonstrated that iFGFR1 activation stimulated recruitment of macrophages to the epithelium where macrophages contributed to iFGFR1-mediated epithelial cell proliferation and angiogenesis. The studies presented here further utilize this model to identify the mechanisms that regulate FGFR1-induced macrophage recruitment. Results from this study elucidate a novel role for the inflammatory chemokine CX3CL1 in FGFR1-induced macrophage migration. Specifically, we illustrate that activation of both the inducible FGFR1 construct in mouse mammary epithelial cells and endogenous FGFR in the triple negative breast cancer cell line, HS578T, leads to expression of the chemokine CX3CL1. Furthermore, we demonstrate that FGFR-induced CX3CL1 is sufficient to recruit CX3CR1-expressing macrophages in vitro. Finally, blocking CX3CR1 in vivo leads to decreased iFGFR1-induced macrophage recruitment, which correlates with decreased angiogenesis. While CX3CL1 is a known target of FGF signaling in the wound healing environment, these studies demonstrate that FGFR activation also leads to induction of CX3CL1 in a tumor setting. Furthermore, these results define a novel role for CX3CL1 in promoting macrophage recruitment during mammary tumor formation, suggesting that the CX3CL1/CX3CR1 axis may represent a potential therapeutic approach for targeting breast cancers associated

  11. β-Carotene Attenuates Angiotensin II-Induced Aortic Aneurysm by Alleviating Macrophage Recruitment in Apoe(-/- Mice.

    Directory of Open Access Journals (Sweden)

    Kaliappan Gopal

    Full Text Available Abdominal aortic aneurysm (AAA is a common chronic degenerative disease characterized by progressive aortic dilation and rupture. The mechanisms underlying the role of α-tocopherol and β-carotene on AAA have not been comprehensively assessed. We investigated if α-tocopherol and β-carotene supplementation could attenuate AAA, and studied the underlying mechanisms utilized by the antioxidants to alleviate AAA. Four-months-old Apoe(-/- mice were used in the induction of aneurysm by infusion of angiotensin II (Ang II, and were orally administered with α-tocopherol and β-carotene enriched diet for 60 days. Significant increase of LDL, cholesterol, triglycerides and circulating inflammatory cells was observed in the Ang II-treated animals, and gene expression studies showed that ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9 and MMP-12 were upregulated in the aorta of aneurysm-induced mice. Extensive plaques, aneurysm and diffusion of inflammatory cells into the tunica intima were also noticed. The size of aorta was significantly (P = 0.0002 increased (2.24±0.20 mm in the aneurysm-induced animals as compared to control mice (1.17±0.06 mm. Interestingly, β-carotene dramatically controlled the diffusion of macrophages into the aortic tunica intima, and circulation. It also dissolved the formation of atheromatous plaque. Further, β-carotene significantly decreased the aortic diameter (1.33±0.12 mm in the aneurysm-induced mice (β-carotene, P = 0.0002. It also downregulated ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9, MMP-12, PPAR-α and PPAR-γ following treatment. Hence, dietary supplementation of β-carotene may have a protective function against Ang II-induced AAA by ameliorating macrophage recruitment in Apoe(-/- mice.

  12. A co-culture system with three different primary human cell populations reveals that biomaterials and MSC modulate macrophage-driven fibroblast recruitment.

    Science.gov (United States)

    Caires, Hugo R; Barros da Silva, Patrícia; Barbosa, Mário A; Almeida, Catarina R

    2018-03-01

    The biological response to implanted biomaterials is a complex and highly coordinated phenomenon involving many different cell types that interact within 3D microenvironments. Here, we increased the complexity of a 3D platform to include at least 3 cell types that play a role in the host response upon scaffold implantation. With this system, it was possible to address how immune responses triggered by 3D biomaterials mediate recruitment of stromal cells that promote tissue regeneration, mesenchymal stromal/stem cells (MSC), or a foreign body response, fibroblasts. Primary human macrophages yielded the highest fibroblast recruitment when interacting with chitosan scaffolds but not polylactic acid. Interestingly, when there were MSC and fibroblasts in the same environment, macrophages in chitosan scaffolds again promoted a significant increase on fibroblast recruitment, but not of MSC. However, macrophages that were firstly allowed to interact with MSC within the scaffolds were no longer able to recruit fibroblasts. This study illustrates the potential to use different scaffolds to regulate the dynamics of recruitment of proregenerative or fibrotic cell types through immunomodulation. Overall, this work strengths the idea that ex vivo predictive systems need to consider the different players involved in the biological response to biomaterials and that timing of arrival of specific cell types will affect the outcome. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Enhancement of wound closure by modifying dual release patterns of stromal-derived cell factor-1 and a macrophage recruitment agent from gelatin hydrogels.

    Science.gov (United States)

    Kim, Yang-Hee; Tabata, Yasuhiko

    2017-11-01

    The objective of the present study is to evaluate the effects of the release patterns of stromal derived factor (SDF)-1 and sphingosine-1 phosphate agonist (SEW2871), used as MSC and macrophage recruitment agents, on the wound closure of diabetic mouse skin defects. To achieve different release patterns, hydrogels were prepared using two types of gelatin with isoelectric points (IEP) of 5 and 9, into which SDF-1 and SEW2871 were then incorporated in various combinations. When the hydrogels incorporating SDF-1 and SEW2871 were applied into wound defects of diabetic mice, the number of MSCs and macrophages recruited to the defects and the levels of pro- and anti- inflammatory cytokines were found to be dependent on the release profiles of SDF-1 and SEW2871. Of particular interest was the case of a rapid release of SDF-1 combined with a controlled release of SEW2871. This resulted in a higher number of M2 macrophages and gene expression levels of anti-inflammatory cytokines 3 days after implantation and faster wound closure than when pairing the controlled release of SDF-1 with a rapid release of SEW2871. Therefore, the present study demonstrates that different release patterns of SDF-1 and SEW2871 can enhance the in vivo recruitment of MSCs and macrophages, and can promote skin wound closure through the modulation of inflammation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Paracrine Interactions between Adipocytes and Tumor Cells Recruit and Modify Macrophages to the Mammary Tumor Microenvironment: The Role of Obesity and Inflammation in Breast Adipose Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Santander, Ana M.; Lopez-Ocejo, Omar; Casas, Olivia; Agostini, Thais; Sanchez, Lidia; Lamas-Basulto, Eduardo; Carrio, Roberto [Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136 (United States); Cleary, Margot P. [Hormel Institute, University of Minnesota, Austin, MN 55912 (United States); Gonzalez-Perez, Ruben R. [Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30314 (United States); Torroella-Kouri, Marta, E-mail: mtorroella@med.miami.edu [Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136 (United States); Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1475 NW 12th Ave, Miami, FL 33136 (United States)

    2015-01-15

    The relationship between obesity and breast cancer (BC) has focused on serum factors. However, the mammary gland contains adipose tissue (AT) which may enable the crosstalk between adipocytes and tumor cells contributing to tumor macrophage recruitment. We hypothesize that the breast AT (bAT) is inflamed in obese females and plays a major role in breast cancer development. The effects of this interplay on macrophage chemotaxis were examined in vitro, using co-cultures of mouse macrophages, mammary tumor cells and adipocytes. Macrophages were exposed to the adipocyte and tumor paracrine factors leptin, CCL2 and lauric acid (alone or in combinations). In cell supernatants Luminex identified additional molecules with chemotactic and other pro-tumor functions. Focus on the adipokine leptin, which has been shown to have a central role in breast cancer pathogenesis, indicated it modulates macrophage phenotypes and functions. In vivo experiments demonstrate that mammary tumors from obese mice are larger and that bAT from obese tumor-bearers contains higher numbers of macrophages/CLS and hypertrophic adipocytes than bAT from lean tumor-bearers, thus confirming it is more inflamed. Also, bAT distal from the tumor is more inflamed in obese than in lean mice. Our results reveal that bAT plays a role in breast cancer development in obesity.

  15. Paracrine Interactions between Adipocytes and Tumor Cells Recruit and Modify Macrophages to the Mammary Tumor Microenvironment: The Role of Obesity and Inflammation in Breast Adipose Tissue

    International Nuclear Information System (INIS)

    Santander, Ana M.; Lopez-Ocejo, Omar; Casas, Olivia; Agostini, Thais; Sanchez, Lidia; Lamas-Basulto, Eduardo; Carrio, Roberto; Cleary, Margot P.; Gonzalez-Perez, Ruben R.; Torroella-Kouri, Marta

    2015-01-01

    The relationship between obesity and breast cancer (BC) has focused on serum factors. However, the mammary gland contains adipose tissue (AT) which may enable the crosstalk between adipocytes and tumor cells contributing to tumor macrophage recruitment. We hypothesize that the breast AT (bAT) is inflamed in obese females and plays a major role in breast cancer development. The effects of this interplay on macrophage chemotaxis were examined in vitro, using co-cultures of mouse macrophages, mammary tumor cells and adipocytes. Macrophages were exposed to the adipocyte and tumor paracrine factors leptin, CCL2 and lauric acid (alone or in combinations). In cell supernatants Luminex identified additional molecules with chemotactic and other pro-tumor functions. Focus on the adipokine leptin, which has been shown to have a central role in breast cancer pathogenesis, indicated it modulates macrophage phenotypes and functions. In vivo experiments demonstrate that mammary tumors from obese mice are larger and that bAT from obese tumor-bearers contains higher numbers of macrophages/CLS and hypertrophic adipocytes than bAT from lean tumor-bearers, thus confirming it is more inflamed. Also, bAT distal from the tumor is more inflamed in obese than in lean mice. Our results reveal that bAT plays a role in breast cancer development in obesity

  16. Washing away your sins in the brain: physical cleaning and priming of cleaning recruit different brain networks after moral threat.

    Science.gov (United States)

    Tang, Honghong; Lu, Xiaping; Su, Rui; Liang, Zilu; Mai, Xiaoqin; Liu, Chao

    2017-07-01

    The association between moral purity and physical cleanliness has been widely discussed recently. Studies found that moral threat initiates the need of physical cleanliness, but actual physical cleaning and priming of cleaning have inconsistent effects on subsequent attitudes and behaviors. Here, we used resting-state functional magnetic resonance imaging to explore the underlying neural mechanism of actual physical cleaning and priming of cleaning. After recalling moral transgression with strong feelings of guilt and shame, participants either actually cleaned their faces with a wipe or were primed with cleanliness through viewing its pictures. Results showed that actual physical cleaning reduced the spontaneous brain activities in the right insula and MPFC, regions that involved in embodied moral emotion processing, while priming of cleaning decreased activities in the right superior frontal gyrus and middle frontal gyrus, regions that participated in executive control processing. Additionally, actual physical cleaning also changed functional connectivity between insula/MPFC and emotion related regions, whereas priming of cleaning modified connectivity within both moral and sensorimotor areas. These findings revealed that actual physical cleaning and priming of cleaning led to changes in different brain regions and networks, providing neural evidence for the inconsistent effects of cleanliness on subsequent attitudes and behaviors. © The Author (2017). Published by Oxford University Press.

  17. A possible mechanism in the recruitment of eosinophils and Th2 cells through CD163(+) M2 macrophages in the lesional skin of eosinophilic cellulitis.

    Science.gov (United States)

    Fujimura, Taku; Kambayashi, Yumi; Furudate, Sadanori; Kakizaki, Aya; Aiba, Setsuya

    2014-01-01

    M2 macrophages play a critical role in the recruitment of T helper 2 (Th2) regulatory T cells (Treg). To study the role of M2 macrophages and Treg cells in eosinophilic celulitis. We employed immunohistochemical staining for CD163( )and CD206 (macrophages) as well as FoxP3 (Treg), in lesional skin of four cases of eosinophilic cellulitis. CD163(+) CD206(+) M2 macrophages, which were previously reported to produce CCL17 to induce Th2 cells and Treg cells, were predominantly infiltrating the subcutaneous tissues and interstitial area of the dermis. M2 macrophages derived from PBMC showed significantly increased expression of CCL11, CCL17, CCL24 and CCL26 mRNA and production of CCL17 and CCL24, when stimulated by IL-4 or IL- 13. In addition, CCL17-producing cells and CCL24-producing cells were prominent in the lesional skin of EC. Our study sheds light on one of the possible immunological mechanisms of eosinophilic cellulitis.

  18. Abscisic acid ameliorates atherosclerosis by suppressing macrophage and CD4+ T cell recruitment into the aortic wall.

    Science.gov (United States)

    Guri, Amir J; Misyak, Sarah A; Hontecillas, Raquel; Hasty, Alyssa; Liu, Dongmin; Si, Hongwei; Bassaganya-Riera, Josep

    2010-12-01

    Abscisic acid (ABA) is a natural phytohormone which improves insulin sensitivity and reduces adipose tissue inflammation when supplemented into diets of obese mice. The objective of this study was to investigate the mechanisms by which ABA prevents or ameliorates atherosclerosis. apolipoprotein E-deficient (ApoE(-/-)) mice were fed high-fat diets with or without ABA for 84 days. Systolic blood pressure was assessed on Days 0, 28, 56 and 72. Gene expression, immune cell infiltration and histological lesions were evaluated in the aortic root wall. Human aortic endothelial cells were used to examine the effect of ABA on 3',5'-cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) production in vitro. We report that ABA-treated mice had significantly improved systolic blood pressure and decreased accumulation of F4/80(+)CD11b(+) macrophages and CD4(+) T cells in aortic root walls. At the molecular level, ABA significantly enhanced aortic endothelial nitric oxide synthase (eNOS) and tended to suppress aortic vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) expression and plasma MCP-1 concentrations. ABA also caused a dose-dependent increase in intracellular concentrations of cAMP and NO and up-regulated eNOS mRNA expression in human aortic endothelial cells. This is the first report showing that ABA prevents or ameliorates atherosclerosis-induced hypertension, immune cell recruitment into the aortic root wall and up-regulates aortic eNOS expression in ApoE(-/-) mice. Copyright © 2010 Elsevier Inc. All rights reserved.

  19. The promotion of mandibular defect healing by the targeting of S1P receptors and the recruitment of alternatively activated macrophages.

    Science.gov (United States)

    Das, Anusuya; Segar, Claire E; Hughley, Brian B; Bowers, Daniel T; Botchwey, Edward A

    2013-12-01

    Endogenous signals originating at the site of injury are involved in the paracrine recruitment, proliferation, and differentiation of circulating progenitor and diverse inflammatory cell types. Here, we investigate a strategy to exploit endogenous cell recruitment mechanisms to regenerate injured bone by local targeting and activation of sphingosine-1-phosphate (S1P) receptors. A mandibular defect model was selected for evaluating regeneration of bone following trauma or congenital disease. The particular challenges of mandibular reconstruction are inherent in the complex anatomy and function of the bone given that the area is highly vascularized and in close proximity to muscle. Nanofibers composed of poly(DL-lactide-co-glycolide) (PLAGA) and polycaprolactone (PCL) were used to delivery FTY720, a targeted agonist of S1P receptors 1 and 3. In vitro culture of bone progenitor cells on drug-loaded constructs significantly enhanced SDF1α mediated chemotaxis of bone marrow mononuclear cells. In vivo results show that local delivery of FTY720 from composite nanofibers enhanced blood vessel ingrowth and increased recruitment of M2 alternatively activated macrophages, leading to significant osseous tissue ingrowth into critical sized defects after 12 weeks of treatment. These results demonstrate that local activation of S1P receptors is a regenerative cue resulting in recruitment of wound healing or anti-inflammatory macrophages and bone healing. Use of such small molecule therapy can provide an alternative to biological factors for the clinical treatment of critical size craniofacial defects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. DMPD: Regulation of phagocyte migration and recruitment by Src-family kinases. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18385944 Regulation of phagocyte migration and recruitment by Src-family kinases. B...how Regulation of phagocyte migration and recruitment by Src-family kinases. PubmedID 18385944 Title Regulat...ion of phagocyte migration and recruitment by Src-family kinases. Authors Baruzzi

  1. Tissue Damage Caused by Myeloablative, but Not Non-Myeloablative, Conditioning before Allogeneic Stem Cell Transplantation Results in Dermal Macrophage Recruitment without Active T-Cell Interaction

    Directory of Open Access Journals (Sweden)

    Peter van Balen

    2018-02-01

    activated APC and donor T-cells, the tissue damage caused by myeloablative alloSCT results in dermal recruitment of HLA class II-positive tissue repairing macrophages co-existing with increased numbers of patient- and donor-derived T-cells, but without signs of specific interaction and initiation of an immune response. Thus, the local skin damage caused by the conditioning regimen appears to be insufficient as single factor to provoke GVHD induction.

  2. In vivo USPIO magnetic resonance imaging shows that minocycline mitigates macrophage recruitment to a peripheral nerve injury

    Directory of Open Access Journals (Sweden)

    Ghanouni Pejman

    2012-06-01

    Full Text Available Abstract Background Minocycline has proven anti-nociceptive effects, but the mechanism by which minocycline delays the development of allodynia and hyperalgesia after peripheral nerve injury remains unclear. Inflammatory cells, in particular macrophages, are critical components of the response to nerve injury. Using ultrasmall superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI to monitor macrophage trafficking, the purpose of this project is to determine whether minocycline modulates macrophage trafficking to the site of nerve injury in vivo and, in turn, results in altered pain thresholds. Results Animal experiments were approved by Stanford IACUC. A model of neuropathic pain was created using the Spared Nerve Injury (SNI model that involves ligation of the left sciatic nerve in the left thigh of adult Sprague–Dawley rats. Animals with SNI and uninjured animals were then injected with/without USPIOs (300 μmol/kg IV and with/without minocycline (50 mg/kg IP. Bilateral sciatic nerves were scanned with a volume coil in a 7 T magnet 7 days after USPIO administration. Fluid-sensitive MR images were obtained, and ROIs were placed on bilateral sciatic nerves to quantify signal intensity. Pain behavior modulation by minocycline was measured using the Von Frey filament test. Sciatic nerves were ultimately harvested at day 7, fixed in 10% buffered formalin and stained for the presence of iron oxide-laden macrophages. Behavioral measurements confirmed the presence of allodynia in the neuropathic pain model while the uninjured and minocycline-treated injured group had significantly higher paw withdrawal thresholds (p  Conclusion Animals with neuropathic pain in the left hindpaw show increased trafficking of USPIO-laden macrophages to the site of sciatic nerve injury. Minocycline to retards the migration of macrophages to the nerve injury site, which may partly explain its anti-nociceptive effects. USPIO-MRI is an effective in

  3. Deficiencies of the lipid-signaling enzymes phospholipase D1 and D2 alter cytoskeletal organization, macrophage phagocytosis, and cytokine-stimulated neutrophil recruitment.

    Directory of Open Access Journals (Sweden)

    Wahida H Ali

    Full Text Available Cell migration and phagocytosis ensue from extracellular-initiated signaling cascades that orchestrate dynamic reorganization of the actin cytoskeleton. The reorganization is mediated by effector proteins recruited to the site of activity by locally-generated lipid second messengers. Phosphatidic acid (PA, a membrane phospholipid generated by multiple enzyme families including Phospholipase D (PLD, has been proposed to function in this role. Here, we show that macrophages prepared from mice lacking either of the classical PLD isoforms PLD1 or PLD2, or wild-type macrophages whose PLD activity has been pharmacologically inhibited, display isoform-specific actin cytoskeleton abnormalities that likely underlie decreases observed in phagocytic capacity. Unexpectedly, PA continued to be detected on the phagosome in the absence of either isoform and even when all PLD activity was eliminated. However, a disorganized phagocytic cup was observed as visualized by imaging PA, F-actin, Rac1, an organizer of the F-actin network, and DOCK2, a Rac1 activator, suggesting that PLD-mediated PA production during phagocytosis is specifically critical for the integrity of the process. The abnormal F-actin reorganization additionally impacted neutrophil migration and extravasation from the vasculature into interstitial tissues. Although both PLD1 and PLD2 were important in these processes, we also observed isoform-specific functions. PLD1-driven processes in particular were observed to be critical in transmigration of macrophages exiting the vasculature during immune responses such as those seen in acute pancreatitis or irritant-induced skin vascularization.

  4. Restoration of prostaglandin E2-producing splenic macrophages in 89Sr-treated mice with bone marrow from Corynebacterium parvum primed donors

    International Nuclear Information System (INIS)

    Shibata, Y.

    1989-01-01

    Administration of Corynebacterium parvum (CP), 56 mg/kg ip to CBA/J mice effected the induction of prostaglandin E2 (PGE2) producing macrophages (M phi) in the bone marrow and the spleen. Maximal release of PGE2 from M phi cultured in vitro with calcium ionophore A23187 for 2 h was reached by marrow M phi removed on 5 days after CP (450 ng/mg cell protein), and by splenic M phi 9 days after CP (400 ng/mg). Neither M phi population, however, yielded more than 6.0 ng/mg leukotriene C4. To assess ontogenic relationships mice were depleted of bone marrow and blood monocytes by iv injection of the bone-seeking isotope, 89Sr. CP was given at several points before or after bone marrow cell depletion. PGE2 production by splenic M phi harvested on day 9 after CP was profoundly impaired when CP was administered either concurrently with or 3 days after 89Sr. When CP was administered 1, 3, 5, and 7 days before 89Sr, however, the induction of PGE2-producing M phi in the spleen was unaffected. To determine whether bone marrow cells from CP-injected donors can restore PGE2-producing splenic M phi (PGSM) in 89Sr-mice, recipient mice which had and had not received CP 3 days after 89Sr were transfused with 5 x 10(6) syngeneic bone marrow cells from donor mice prepared at varying intervals after CP administration. The results clearly indicate the capacity of bone marrow cells harvested on either day 1 or 2 following CP to restore PGSM in CP-primed, but not unprimed, recipients

  5. Foliar aphid feeding recruits rhizosphere bacteria and primes plant immunity against pathogenic and non-pathogenic bacteria in pepper.

    Science.gov (United States)

    Lee, Boyoung; Lee, Soohyun; Ryu, Choong-Min

    2012-07-01

    Plants modulate defence signalling networks in response to different biotic stresses. The present study evaluated the effect of a phloem-sucking aphid on plant defence mechanisms in pepper (Capsicum annuum) during subsequent pathogen attacks on leaves and rhizosphere bacteria on roots. Plants were pretreated with aphids and/or the chemical trigger benzothiadiazol (BTH) 7 d before being challenged with two pathogenic bacteria, Xanthomonas axonopodis pv. vesicatoria (Xav) as a compatible pathogen and X. axonopodis pv. glycines (Xag) as an incompatible (non-host) pathogen. Disease severity was noticeably lower in aphid- and BTH + aphid-treated plants than in controls. Although treatment with BTH or aphids alone did not affect the hypersensitive response (HR) against Xag strain 8ra, the combination treatment had a synergistic effect on the HR. The aphid population was reduced by BTH pretreatment and by combination treatment with BTH and bacterial pathogens in a synergistic manner. Analysis of the expression of the defence-related genes Capsicum annum pathogenesis-related gene 9 (CaPR9), chitinase 2 (CaCHI2), SAR8·2 and Lipoxygenase1 (CaLOX1) revealed that aphid infestation resulted in the priming of the systemic defence responses against compatible and incompatible pathogens. Conversely, pre-challenge with the compatible pathogen Xav on pepper leaves significantly reduced aphid numbers. Aphid infestation increased the population of the beneficial Bacillus subtilis GB03 but reduced that of the pathogenic Ralstonia solanacearum SL1931. The expression of defence-related genes in the root and leaf after aphid feeding indicated that the above-ground aphid infestation elicited salicylic acid and jasmonic acid signalling throughout the whole plant. The findings of this study show that aphid feeding elicits plant resistance responses and attracts beneficial bacterial populations to help the plant cope with subsequent pathogen attacks.

  6. Allele-Selective Transcriptome Recruitment to Polysomes Primed for Translation: Protein-Coding and Noncoding RNAs, and RNA Isoforms.

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    Roshan Mascarenhas

    Full Text Available mRNA translation into proteins is highly regulated, but the role of mRNA isoforms, noncoding RNAs (ncRNAs, and genetic variants remains poorly understood. mRNA levels on polysomes have been shown to correlate well with expressed protein levels, pointing to polysomal loading as a critical factor. To study regulation and genetic factors of protein translation we measured levels and allelic ratios of mRNAs and ncRNAs (including microRNAs in lymphoblast cell lines (LCL and in polysomal fractions. We first used targeted assays to measure polysomal loading of mRNA alleles, confirming reported genetic effects on translation of OPRM1 and NAT1, and detecting no effect of rs1045642 (3435C>T in ABCB1 (MDR1 on polysomal loading while supporting previous results showing increased mRNA turnover of the 3435T allele. Use of high-throughput sequencing of complete transcript profiles (RNA-Seq in three LCLs revealed significant differences in polysomal loading of individual RNA classes and isoforms. Correlated polysomal distribution between protein-coding and non-coding RNAs suggests interactions between them. Allele-selective polysome recruitment revealed strong genetic influence for multiple RNAs, attributable either to differential expression of RNA isoforms or to differential loading onto polysomes, the latter defining a direct genetic effect on translation. Genes identified by different allelic RNA ratios between cytosol and polysomes were enriched with published expression quantitative trait loci (eQTLs affecting RNA functions, and associations with clinical phenotypes. Polysomal RNA-Seq combined with allelic ratio analysis provides a powerful approach to study polysomal RNA recruitment and regulatory variants affecting protein translation.

  7. Alveolar macrophage-epithelial cell interaction following exposure to atmospheric particles induces the release of mediators involved in monocyte mobilization and recruitment

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    Mukae Hiroshi

    2005-08-01

    Full Text Available Abstract Background Studies from our laboratory have shown that human alveolar macrophages (AM and bronchial epithelial cells (HBEC exposed to ambient particles (PM10 in vitro increase their production of inflammatory mediators and that supernatants from PM10-exposed cells shorten the transit time of monocytes through the bone marrow and promote their release into the circulation. Methods The present study concerns co-culture of AM and HBEC exposed to PM10 (EHC-93 and the production of mediators involved in monocyte kinetics measured at both the mRNA and protein levels. The experiments were also designed to determine the role of the adhesive interaction between these cells via the intercellular adhesion molecule (ICAM-1 in the production of these mediators. Results AM/HBEC co-cultures exposed to 100 μg/ml of PM10 for 2 or 24 h increased their levels of granulocyte-macrophage colony-stimulating factor (GM-CSF, M-CSF, macrophage inflammatory protein (MIP-1β, monocyte chemotactic protein (MCP-1, interleukin (IL-6 and ICAM-1 mRNA, compared to exposed AM or HBEC mono-cultures, or control non-exposed co-cultures. The levels of GM-CSF, M-CSF, MIP-1β and IL-6 increased in co-cultured supernatants collected after 24 h exposure compared to control cells (p 10-induced increase in co-culture mRNA expression. Conclusion We conclude that an ICAM-1 independent interaction between AM and HBEC, lung cells that process inhaled particles, increases the production and release of mediators that enhance bone marrow turnover of monocytes and their recruitment into tissues. We speculate that this interaction amplifies PM10-induced lung inflammation and contributes to both the pulmonary and systemic morbidity associated with exposure to air pollution.

  8. Proliferating macrophages prevail in atherosclerosis.

    Science.gov (United States)

    Randolph, Gwendalyn J

    2013-09-01

    Macrophages accumulate in atherosclerotic lesions during the inflammation that is part of atherosclerosis development and progression. A new study in mice indicates that the accumulation of macrophages in atherosclerotic plaques depends on local macrophage proliferation rather than the recruitment of circulating monocytes.

  9. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    Energy Technology Data Exchange (ETDEWEB)

    Khatami, Mahin [Inflammation and Cancer Biology, National Cancer Institute (Ret), the National Institutes of Health, Bethesda, MD 20817 (United States)

    2014-01-27

    Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates) is heavy investment on numerous genetic mutations (molecular false-flags) in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance). Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs) demonstrated at least three stages of interactions between resident (host) and recruited immune cells: (a), acute phase; activation of mast cells (MCs), IgE Abs, histamine and prostaglandin synthesis; (b), intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos) infiltrations into epithelia and goblet cells (GCs), tissue hypertrophy and neovascularization; and (c), chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mϕs), increased (irregular size) B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth) and/or thinning (necrosis) and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune

  10. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs and Eosinophils (Eos with Host Mast Cells (MCs and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    Directory of Open Access Journals (Sweden)

    Mahin Khatami

    2014-01-01

    Full Text Available Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates is heavy investment on numerous genetic mutations (molecular false-flags in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance. Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs demonstrated at least three stages of interactions between resident (host and recruited immune cells: (a, acute phase; activation of mast cells (MCs, IgE Abs, histamine and prostaglandin synthesis; (b, intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos infiltrations into epithelia and goblet cells (GCs, tissue hypertrophy and neovascularization; and (c, chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mfs, increased (irregular size B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth and/or thinning (necrosis and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune

  11. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    International Nuclear Information System (INIS)

    Khatami, Mahin

    2014-01-01

    Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates) is heavy investment on numerous genetic mutations (molecular false-flags) in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance). Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs) demonstrated at least three stages of interactions between resident (host) and recruited immune cells: (a), acute phase; activation of mast cells (MCs), IgE Abs, histamine and prostaglandin synthesis; (b), intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos) infiltrations into epithelia and goblet cells (GCs), tissue hypertrophy and neovascularization; and (c), chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mϕs), increased (irregular size) B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth) and/or thinning (necrosis) and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune

  12. Targeted blockade in lethal West Nile virus encephalitis indicates a crucial role for very late antigen (VLA-4-dependent recruitment of nitric oxide-producing macrophages

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    Getts Daniel R

    2012-10-01

    Full Text Available Abstract Infiltration of Ly6Chi monocytes from the blood is a hallmark of viral encephalitis. In mice with lethal encephalitis caused by West Nile virus (WNV, an emerging neurotropic flavivirus, inhibition of Ly6Chi monocyte trafficking into the brain by anti-very late antigen (VLA-4 integrin antibody blockade at the time of first weight loss and leukocyte influx resulted in long-term survival of up to 60% of infected mice, with subsequent sterilizing immunity. This treatment had no effect on viral titers but appeared to be due to inhibition of Ly6Chi macrophage immigration. Although macrophages isolated from the infected brain induced WNV-specific CD4+ T-cell proliferation, T cells did not directly contribute to pathology, but are likely to be important in viral control, as antibody-mediated T-cell depletion could not reproduce the therapeutic benefit of anti-VLA-4. Instead, 70% of infiltrating inflammatory monocyte-derived macrophages were found to be making nitric oxide (NO. Furthermore, aminoguanidine-mediated inhibition of induced NO synthase activity in infiltrating macrophages significantly prolonged survival, indicating involvement of NO in the immunopathology. These data show for the first time the therapeutic effects of temporally targeting pathogenic NO-producing macrophages during neurotropic viral encephalitis.

  13. CXC-chemokines KC and macrophage inflammatory protein-2 (MIP-2) synergistically induce leukocyte recruitment to the central nervous system in rats

    NARCIS (Netherlands)

    Zwijnenburg, Petra J. G.; Polfliet, Machteld M. J.; Florquin, Sandrine; van den Berg, Timo K.; Dijkstra, Christine D.; van Deventer, Sander J. H.; Roord, John J.; van der Poll, Tom; van Furth, A. Marceline

    2003-01-01

    Intracisternal injection of the CXC-chemokines KC or macrophage inflammatory protein (MIP)-2 induced a pleocytosis in the cerebrospinal fluid (CSF) of rats in a dose dependent way. MIP-2 was much more potent than KC. The concurrent injection of both chemokines revealed a profound synergistic effect

  14. Role of interferon-gamma in the pathogenesis of LCMV-induced meningitis: unimpaired leucocyte recruitment, but deficient macrophage activation in interferon-gamma knock-out mice

    DEFF Research Database (Denmark)

    Nansen, A; Christensen, Jan Pravsgaard; Röpke, C

    1998-01-01

    , a viral peptide could also elicit a T cell mediated inflammatory response in virus-primed IFN-gamma knock-out mice, indicating that redundancy of this cytokine as a proinflammatory mediator is not restricted to inflammatory reactions triggered by an active infection. Thus, T cell mediated inflammation may...

  15. The thyroid hormone triiodothyronine controls macrophage maturation and functions: protective role during inflammation.

    Science.gov (United States)

    Perrotta, Cristiana; Buldorini, Marcella; Assi, Emma; Cazzato, Denise; De Palma, Clara; Clementi, Emilio; Cervia, Davide

    2014-01-01

    The endocrine system participates in regulating macrophage maturation, although little is known about the modulating role of the thyroid hormones. In vitro results demonstrate a negative role of one such hormone, triiodothyronine (T3), in triggering the differentiation of bone marrow-derived monocytes into unpolarized macrophages. T3-induced macrophages displayed a classically activated (M1) signature. A T3-induced M1-priming effect was also observed on polarized macrophages because T3 reverses alternatively activated (M2) activation, whereas it enhances that of M1 cells. In vivo, circulating T3 increased the content of the resident macrophages in the peritoneal cavity, whereas it reduced the content of the recruited monocyte-derived cells. Of interest, T3 significantly protected mice against endotoxemia induced by lipopolysaccharide i.p. injection; in these damaged animals, decreased T3 levels increased the recruited (potentially damaging) cells, whereas restoring T3 levels decreased recruited and increased resident (potentially beneficial) cells. These data suggest that the anti-inflammatory effect of T3 is coupled to the modulation of peritoneal macrophage content, in a context not fully explained by the M1/M2 framework. Thyroid hormone receptor expression analysis and the use of different thyroid hormone receptor antagonists suggest thyroid hormone receptor β1 as the major player mediating T3 effects on macrophages. The novel homeostatic link between thyroid hormones and the pathophysiological role of macrophages opens new perspectives on the interactions between the endocrine and immune systems. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  16. Macrophage colony-stimulating factor augments Tie2-expressing monocyte differentiation, angiogenic function, and recruitment in a mouse model of breast cancer.

    Science.gov (United States)

    Forget, Mary A; Voorhees, Jeffrey L; Cole, Sara L; Dakhlallah, Duaa; Patterson, Ivory L; Gross, Amy C; Moldovan, Leni; Mo, Xiaokui; Evans, Randall; Marsh, Clay B; Eubank, Tim D

    2014-01-01

    Reports demonstrate the role of M-CSF (CSF1) in tumor progression in mouse models as well as the prognostic value of macrophage numbers in breast cancer patients. Recently, a subset of CD14+ monocytes expressing the Tie2 receptor, once thought to be predominantly expressed on endothelial cells, has been characterized. We hypothesized that increased levels of CSF1 in breast tumors can regulate differentiation of Tie2- monocytes to a Tie2+ phenotype. We treated CD14+ human monocytes with CSF1 and found a significant increase in CD14+/Tie2+ positivity. To understand if CSF1-induced Tie2 expression on these cells improved their migratory ability, we pre-treated CD14+ monocytes with CSF1 and used Boyden chemotaxis chambers to observe enhanced response to angiopoietin-2 (ANG2), the chemotactic ligand for the Tie2 receptor. We found that CSF1 pre-treatment significantly augmented chemotaxis and that Tie2 receptor upregulation was responsible as siRNA targeting Tie2 receptor abrogated this effect. To understand any augmented angiogenic effect produced by treating these cells with CSF1, we cultured human umbilical vein endothelial cells (HUVECs) with conditioned supernatants from CSF1-pre-treated CD14+ monocytes for a tube formation assay. While supernatants from CSF1-pre-treated TEMs increased HUVEC branching, a neutralizing antibody against the CSF1R abrogated this activity, as did siRNA against the Tie2 receptor. To test our hypothesis in vivo, we treated PyMT tumor-bearing mice with CSF1 and observed an expansion in the TEM population relative to total F4/80+ cells, which resulted in increased angiogenesis. Investigation into the mechanism of Tie2 receptor upregulation on CD14+ monocytes by CSF1 revealed a synergistic contribution from the PI3 kinase and HIF pathways as the PI3 kinase inhibitor LY294002, as well as HIF-1α-deficient macrophages differentiated from the bone marrow of HIF-1αfl/fl/LysMcre mice, diminished CSF1-stimulated Tie2 receptor expression.

  17. Macrophage colony-stimulating factor augments Tie2-expressing monocyte differentiation, angiogenic function, and recruitment in a mouse model of breast cancer.

    Directory of Open Access Journals (Sweden)

    Mary A Forget

    Full Text Available Reports demonstrate the role of M-CSF (CSF1 in tumor progression in mouse models as well as the prognostic value of macrophage numbers in breast cancer patients. Recently, a subset of CD14+ monocytes expressing the Tie2 receptor, once thought to be predominantly expressed on endothelial cells, has been characterized. We hypothesized that increased levels of CSF1 in breast tumors can regulate differentiation of Tie2- monocytes to a Tie2+ phenotype. We treated CD14+ human monocytes with CSF1 and found a significant increase in CD14+/Tie2+ positivity. To understand if CSF1-induced Tie2 expression on these cells improved their migratory ability, we pre-treated CD14+ monocytes with CSF1 and used Boyden chemotaxis chambers to observe enhanced response to angiopoietin-2 (ANG2, the chemotactic ligand for the Tie2 receptor. We found that CSF1 pre-treatment significantly augmented chemotaxis and that Tie2 receptor upregulation was responsible as siRNA targeting Tie2 receptor abrogated this effect. To understand any augmented angiogenic effect produced by treating these cells with CSF1, we cultured human umbilical vein endothelial cells (HUVECs with conditioned supernatants from CSF1-pre-treated CD14+ monocytes for a tube formation assay. While supernatants from CSF1-pre-treated TEMs increased HUVEC branching, a neutralizing antibody against the CSF1R abrogated this activity, as did siRNA against the Tie2 receptor. To test our hypothesis in vivo, we treated PyMT tumor-bearing mice with CSF1 and observed an expansion in the TEM population relative to total F4/80+ cells, which resulted in increased angiogenesis. Investigation into the mechanism of Tie2 receptor upregulation on CD14+ monocytes by CSF1 revealed a synergistic contribution from the PI3 kinase and HIF pathways as the PI3 kinase inhibitor LY294002, as well as HIF-1α-deficient macrophages differentiated from the bone marrow of HIF-1αfl/fl/LysMcre mice, diminished CSF1-stimulated Tie2 receptor

  18. Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages

    Directory of Open Access Journals (Sweden)

    Hirokazu Nakatsumi

    2017-11-01

    Full Text Available C-C chemokine ligand 2 (CCL2 plays pivotal roles in tumor formation, progression, and metastasis. Although CCL2 expression has been found to be dependent on the nuclear factor (NF-κB signaling pathway, the regulation of CCL2 production in tumor cells has remained unclear. We have identified a noncanonical pathway for regulation of CCL2 production that is mediated by mammalian target of rapamycin complex 1 (mTORC1 but independent of NF-κB. Multiple phosphoproteomics approaches identified the transcription factor forkhead box K1 (FOXK1 as a downstream target of mTORC1. Activation of mTORC1 induces dephosphorylation of FOXK1, resulting in transactivation of the CCL2 gene. Inhibition of the mTORC1-FOXK1 axis attenuated insulin-induced CCL2 production as well as the accumulation of tumor-associated monocytes-macrophages and tumor progression in mice. Our results suggest that FOXK1 directly links mTORC1 signaling and CCL2 expression in a manner independent of NF-κB and that CCL2 produced by this pathway contributes to tumor progression.

  19. Prime Slaughter

    DEFF Research Database (Denmark)

    Valente, Andrea; Marchetti, Emanuela

    2011-01-01

    of primality and factorization into playful interactions, addressed to primary and early secondary school children. Taking into account individual needs expressed by children regarding play, during a participatory design processes aimed at enhancing learning in museums, Prime Slaughter allows for multiple......Starting from the difficulty of creating playful representation of domain-specific abstract concepts, this study discusses the design of Prime Slaughter, a computer game aimed at facilitating individual sense-making of abstract mathematical concepts. Specifically the game proposes a transposition...

  20. Syntactic Priming.

    Science.gov (United States)

    Nicol, Janet L.

    1996-01-01

    Reviews the syntactic priming task, a paradigm involving the presentation of a phrasal or clausal context, followed by the presentation of a target item for lexical decision or naming. Notes that response times are faster for targets syntactically congruent with the preceding context than for incongruent targets. Outlines how to administer this…

  1. Stress-Induced Recruitment of Bone Marrow-Derived Monocytes to the Brain Promotes Anxiety-Like Behavior

    Science.gov (United States)

    Wohleb, Eric S.; Powell, Nicole D.

    2013-01-01

    Social stress is associated with altered immunity and higher incidence of anxiety-related disorders. Repeated social defeat (RSD) is a murine stressor that primes peripheral myeloid cells, activates microglia, and induces anxiety-like behavior. Here we show that RSD-induced anxiety-like behavior corresponded with an exposure-dependent increase in circulating monocytes (CD11b+/SSClo/Ly6Chi) and brain macrophages (CD11b+/SSClo/CD45hi). Moreover, RSD-induced anxiety-like behavior corresponded with brain region-dependent cytokine and chemokine responses involved with myeloid cell recruitment. Next, LysM-GFP+ and GFP+ bone marrow (BM)-chimeric mice were used to determine the neuroanatomical distribution of peripheral myeloid cells recruited to the brain during RSD. LysM-GFP+ mice showed that RSD increased recruitment of GFP+ macrophages to the brain and increased their presence within the perivascular space (PVS). In addition, RSD promoted recruitment of GFP+ macrophages into the PVS and parenchyma of the prefrontal cortex, amygdala, and hippocampus of GFP+ BM-chimeric mice. Furthermore, mice deficient in chemokine receptors associated with monocyte trafficking [chemokine receptor-2 knockout (CCR2KO) or fractalkine receptor knockout (CX3CR1KO)] failed to recruit macrophages to the brain and did not develop anxiety-like behavior following RSD. Last, RSD-induced macrophage trafficking was prevented in BM-chimeric mice generated with CCR2KO or CX3CR1KO donor cells. These findings indicate that monocyte recruitment to the brain in response to social stress represents a novel cellular mechanism that contributes to the development of anxiety. PMID:23966702

  2. The ischemic environment drives microglia and macrophage function

    Directory of Open Access Journals (Sweden)

    Stefano eFumagalli

    2015-04-01

    Full Text Available Cells of myeloid origin such as microglia and macrophages act at the crossroads of several inflammatory mechanisms during pathophysiology. Besides pro-inflammatory activity (M1 polarization, myeloid cells acquire protective functions (M2 and participate in the neuroprotective innate mechanisms after brain injury. Experimental research is making considerable efforts to understand the rules that regulate the balance between toxic and protective brain innate immunity. Environmental changes affects microglia/macrophage functions. Hypoxia can affect myeloid cell distribution, activity and phenotype. With their intrinsic differences, microglia and macrophages respond differently to hypoxia, the former depending on ATP to activate, the latter switching to anaerobic metabolism and adapting to hypoxia. Myeloid cell functions include homeostasis control, damage-sensing activity, chemotaxis and phagocytosis, all distinctive features of these cells. Specific markers and morphologies enable to recognize each functional state. To ensure homeostasis and activate when needed, microglia/macrophage physiology is finely tuned. Microglia are controlled by several neuron-derived components, including contact-dependent inhibitory signals and soluble molecules. Changes in this control can cause chronic activation or priming with specific functional consequences. Strategies such as stem cell treatment may enhance microglia protective polarization. This review presents data from the literature that has greatly advanced our understanding of myeloid cell action in brain injury. We discuss the selective responses of microglia and macrophages to hypoxia after stroke and review relevant markers with the aim of defining the different subpopulations of myeloid cells that are recruited to the injured site. We also cover the functional consequences of chronically active microglia and review pivotal works on microglia regulation that offer new therapeutic possibilities for acute

  3. Prime Slaughter

    DEFF Research Database (Denmark)

    Valente, Andrea; Marchetti, Emanuela

    2011-01-01

    of primality and factorization into playful interactions, addressed to primary and early secondary school children. Taking into account individual needs expressed by children regarding play, during a participatory design processes aimed at enhancing learning in museums, Prime Slaughter allows for multiple...... forms of play and their integration. A simple working prototype has already been developed; it will be tested and re-designed through participatory workshops, involving a group of children in our target group....

  4. Gossypol induces pyroptosis in mouse macrophages via a non-canonical inflammasome pathway

    International Nuclear Information System (INIS)

    Lin, Qiu-Ru; Li, Chen-Guang; Zha, Qing-Bing; Xu, Li-Hui; Pan, Hao; Zhao, Gao-Xiang; Ouyang, Dong-Yun; He, Xian-Hui

    2016-01-01

    Gossypol, a polyphenolic compound isolated from cottonseeds, has been reported to possess many pharmacological activities, but whether it can influence inflammasome activation remains unclear. In this study, we found that in mouse macrophages, gossypol induced cell death characterized by rapid membrane rupture and robust release of HMGB1 and pro-caspase-11 comparable to ATP treatment, suggesting an induction of pyroptotic cell death. Unlike ATP, gossypol induced much low levels of mature interleukin-1β (IL-1β) secretion from mouse peritoneal macrophages primed with LPS, although it caused pro-IL-1β release similar to that of ATP. Consistent with this, activated caspase-1 responsible for pro-IL-1β maturation was undetectable in gossypol-treated peritoneal macrophages. Besides, RAW 264.7 cells lacking ASC expression and caspase-1 activation also underwent pyroptotic cell death upon gossypol treatment. In further support of pyroptosis induction, both pan-caspase inhibitor and caspase-1 subfamily inhibitor, but not caspase-3 inhibitor, could sharply suppress gossypol-induced cell death. Other canonical pyroptotic inhibitors, including potassium chloride and N-acetyl-L-cysteine, could suppress ATP-induced pyroptosis but failed to inhibit or even enhanced gossypol-induced cell death, whereas nonspecific pore-formation inhibitor glycine could attenuate this process, suggesting involvement of a non-canonical pathway. Of note, gossypol treatment eliminated thioglycollate-induced macrophages in the peritoneal cavity with recruitment of other leukocytes. Moreover, gossypol administration markedly decreased the survival of mice in a bacterial sepsis model. Collectively, these results suggested that gossypol induced pyroptosis in mouse macrophages via a non-canonical inflammasome pathway, which raises a concern for its in vivo cytotoxicity to macrophages. - Highlights: • Gossypol induces pyroptosis in mouse peritoneal and RAW 264.7 macrophages. • In LPS-primed

  5. Gossypol induces pyroptosis in mouse macrophages via a non-canonical inflammasome pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Qiu-Ru; Li, Chen-Guang [Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Zha, Qing-Bing [Department of Fetal Medicine, The First Affiliated Hospital of Jinan University, Guangzhou 510632 (China); Xu, Li-Hui [Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Pan, Hao; Zhao, Gao-Xiang [Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Ouyang, Dong-Yun, E-mail: dongyun1967@aliyun.com [Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); He, Xian-Hui, E-mail: thexh@jnu.edu.cn [Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China)

    2016-02-01

    Gossypol, a polyphenolic compound isolated from cottonseeds, has been reported to possess many pharmacological activities, but whether it can influence inflammasome activation remains unclear. In this study, we found that in mouse macrophages, gossypol induced cell death characterized by rapid membrane rupture and robust release of HMGB1 and pro-caspase-11 comparable to ATP treatment, suggesting an induction of pyroptotic cell death. Unlike ATP, gossypol induced much low levels of mature interleukin-1β (IL-1β) secretion from mouse peritoneal macrophages primed with LPS, although it caused pro-IL-1β release similar to that of ATP. Consistent with this, activated caspase-1 responsible for pro-IL-1β maturation was undetectable in gossypol-treated peritoneal macrophages. Besides, RAW 264.7 cells lacking ASC expression and caspase-1 activation also underwent pyroptotic cell death upon gossypol treatment. In further support of pyroptosis induction, both pan-caspase inhibitor and caspase-1 subfamily inhibitor, but not caspase-3 inhibitor, could sharply suppress gossypol-induced cell death. Other canonical pyroptotic inhibitors, including potassium chloride and N-acetyl-L-cysteine, could suppress ATP-induced pyroptosis but failed to inhibit or even enhanced gossypol-induced cell death, whereas nonspecific pore-formation inhibitor glycine could attenuate this process, suggesting involvement of a non-canonical pathway. Of note, gossypol treatment eliminated thioglycollate-induced macrophages in the peritoneal cavity with recruitment of other leukocytes. Moreover, gossypol administration markedly decreased the survival of mice in a bacterial sepsis model. Collectively, these results suggested that gossypol induced pyroptosis in mouse macrophages via a non-canonical inflammasome pathway, which raises a concern for its in vivo cytotoxicity to macrophages. - Highlights: • Gossypol induces pyroptosis in mouse peritoneal and RAW 264.7 macrophages. • In LPS-primed

  6. The Neutrophil Response Induced by an Agonist for Free Fatty Acid Receptor 2 (GPR43) Is Primed by Tumor Necrosis Factor Alpha and by Receptor Uncoupling from the Cytoskeleton but Attenuated by Tissue Recruitment

    DEFF Research Database (Denmark)

    Björkman, Lena; Mårtensson, Jonas; Winther, Malene

    2016-01-01

    by tumor necrosis factor alpha (TNF-α) in a process associated with a recruitment of easily mobilizable granules, but neutrophils recruited to an aseptic inflammation in vivo were nonresponding. Superoxide production induced by Cmp1 was increased in latrunculin A-treated neutrophils, but no reactivation...

  7. Macrophage Plasticity in Skeletal Muscle Repair

    Directory of Open Access Journals (Sweden)

    Elena Rigamonti

    2014-01-01

    Full Text Available Macrophages are one of the first barriers of host defence against pathogens. Beyond their role in innate immunity, macrophages play increasingly defined roles in orchestrating the healing of various injured tissues. Perturbations of macrophage function and/or activation may result in impaired regeneration and fibrosis deposition as described in several chronic pathological diseases. Heterogeneity and plasticity have been demonstrated to be hallmarks of macrophages. In response to environmental cues they display a proinflammatory (M1 or an alternative anti-inflammatory (M2 phenotype. A lot of evidence demonstrated that after acute injury M1 macrophages infiltrate early to promote the clearance of necrotic debris, whereas M2 macrophages appear later to sustain tissue healing. Whether the sequential presence of two different macrophage populations results from a dynamic shift in macrophage polarization or from the recruitment of new circulating monocytes is a subject of ongoing debate. In this paper, we discuss the current available information about the role that different phenotypes of macrophages plays after injury and during the remodelling phase in different tissue types, with particular attention to the skeletal muscle.

  8. Wip1-dependent modulation of macrophage migration and phagocytosis

    DEFF Research Database (Denmark)

    Tang, Yiting; Pan, Bing; Zhou, Xin

    2017-01-01

    Macrophage accumulation within the vascular wall is a hallmark of atherosclerosis. Controlling macrophage conversion into foam cells remains a major challenge for treatment of atherosclerotic diseases. Here, we show that Wip1, a member of the PP2C family of Ser/Thr protein phosphatases, modulates...... macrophage migration and phagocytosis associated with atherosclerotic plaque formation. Wip1 deficiency increases migratory and phagocytic activities of the macrophage under stress conditions. Enhanced migration of Wip1-/- macrophages is mediated by Rac1-GTPase and PI3K/AKT signalling pathways. Elevated...... phagocytic ability of Wip1-/- macrophages is linked to CD36 plasma membrane recruitment that is regulated by AMPK activity. Our study identifies Wip1 as an intrinsic negative regulator of macrophage chemotaxis. We propose that Wip1-dependent control of macrophage function may provide avenues for preventing...

  9. Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome Analysis

    Directory of Open Access Journals (Sweden)

    Yuri V. Bobryshev

    2016-01-01

    Full Text Available Atherosclerosis can be regarded as a chronic inflammatory state, in which macrophages play different and important roles. Phagocytic proinflammatory cells populate growing atherosclerotic lesions, where they actively participate in cholesterol accumulation. Moreover, macrophages promote formation of complicated and unstable plaques by maintaining proinflammatory microenvironment. At the same time, anti-inflammatory macrophages contribute to tissue repair and remodelling and plaque stabilization. Macrophages therefore represent attractive targets for development of antiatherosclerotic therapy, which can aim to reduce monocyte recruitment to the lesion site, inhibit proinflammatory macrophages, or stimulate anti-inflammatory responses and cholesterol efflux. More studies are needed, however, to create a comprehensive classification of different macrophage phenotypes and to define their roles in the pathogenesis of atherosclerosis. In this review, we provide an overview of the current knowledge on macrophage diversity, activation, and plasticity in atherosclerosis and describe macrophage-based cellular tests for evaluation of potential antiatherosclerotic substances.

  10. Employee recruitment.

    Science.gov (United States)

    Breaugh, James A

    2013-01-01

    The way an organization recruits can influence the type of employees it hires, how they perform, and their retention rate. This article provides a selective review of research that has addressed recruitment targeting, recruitment methods, the recruitment message, recruiters, the organizational site visit, the job offer, and the timing of recruitment actions. These and other topics (e.g., the job applicant's perspective) are discussed in terms of their potential influence on prehire (e.g., the quality of job applicants) and posthire (e.g., new employee retention) recruitment outcomes. In reviewing research, attention is given to the current state of scientific knowledge, limitations of previous research, and important issues meriting future investigation.

  11. Endometriosis, a disease of the macrophage

    Directory of Open Access Journals (Sweden)

    Annalisa eCapobianco

    2013-01-01

    Full Text Available Endometriosis, a common cause of pelvic pain and female infertility, depends on the growth of vascularised endometrial tissue at ectopic sites. Endometrial fragments reach the peritoneal cavity during the fertile years: local cues decide whether they yield endometriotic lesions. Macrophages are recruited at sites of hypoxia and tissue stress, where they clear cell debris and heme-iron and generate pro-life and pro-angiogenesis signals. Macrophages are abundant in endometriotic lesions, where are recruited and undergo alternative activation. In rodents macrophages are required for lesions to establish and to grow; bone-marrow derived Tie-2 expressing macrophages specifically contribute to lesions neovasculature, possibly because they concur to the recruitment of circulating endothelial progenitors, and sustain their survival and the integrity of the vessel wall. Macrophages sense cues (hypoxia, cell death, iron overload in the lesions and react delivering signals to restore the local homeostasis: their action represents a necessary, non-redundant step in the natural history of the disease. Endometriosis may be due to a misperception of macrophages about ectopic endometrial tissue. They perceive it as a wound, they activate programs leading to ectopic cell survival and tissue vascularization. Clearing this misperception is a critical area for the development of novel medical treatments of endometriosis, an urgent and unmet medical need.

  12. Recruiting intensity

    OpenAIRE

    R. Jason Faberman

    2014-01-01

    To hire new workers, employers use a variety of recruiting methods in addition to posting a vacancy announcement. The intensity with which employers use these alternative methods can vary widely with a firm’s performance and with the business cycle. In fact, persistently low recruiting intensity helps to explain the sluggish pace of US job growth following the Great Recession.

  13. Omega-3 free fatty acids suppress macrophage inflammasome activation by inhibiting NF-κB activation and enhancing autophagy.

    Directory of Open Access Journals (Sweden)

    Yolanda Williams-Bey

    Full Text Available The omega-3 (ω3 fatty acid docosahexaenoic acid (DHA can suppress inflammation, specifically IL-1β production through poorly understood molecular mechanisms. Here, we show that DHA reduces macrophage IL-1β production by limiting inflammasome activation. Exposure to DHA reduced IL-1β production by ligands that stimulate the NLRP3, AIM2, and NAIP5/NLRC4 inflammasomes. The inhibition required Free Fatty Acid Receptor (FFAR 4 (also known as GPR120, a G-protein coupled receptor (GPR known to bind DHA. The exposure of cells to DHA recruited the adapter protein β-arrestin1/2 to FFAR4, but not to a related lipid receptor. DHA treatment reduced the initial inflammasome priming step by suppressing the nuclear translocation of NF-κB. DHA also reduced IL-1β levels by enhancing autophagy in the cells. As a consequence macrophages derived from mice lacking the essential autophagy protein ATG7 were partially resistant to suppressive effects of DHA. Thus, DHA suppresses inflammasome activation by two distinct mechanisms, inhibiting the initial priming step and by augmenting autophagy, which limits inflammasome activity.

  14. Prime tight frames

    DEFF Research Database (Denmark)

    Lemvig, Jakob; Miller, Christopher; Okoudjou, Kasso A.

    2014-01-01

    to suggest effective analysis and synthesis computation strategies for such frames. Finally, we describe all prime frames constructed from the spectral tetris method, and, as a byproduct, we obtain a characterization of when the spectral tetris construction works for redundancies below two.......We introduce a class of finite tight frames called prime tight frames and prove some of their elementary properties. In particular, we show that any finite tight frame can be written as a union of prime tight frames. We then characterize all prime harmonic tight frames and use thischaracterization...

  15. Priming Ability Emotional Intelligence

    Science.gov (United States)

    Schutte, Nicola S.; Malouff, John M.

    2012-01-01

    Two studies examined whether priming self-schemas relating to successful emotional competency results in better emotional intelligence performance. In the first study participants were randomly assigned to a successful emotional competency self-schema prime condition or a control condition and then completed an ability measure of emotional…

  16. Recognizing Plant Defense Priming

    NARCIS (Netherlands)

    Martinez-Medina, Ainhoa; Flors, Victor; Heil, Martin; Mauch-Mani, Brigitte; Pieterse, Corné M J|info:eu-repo/dai/nl/113115113; Pozo, Maria J; Ton, Jurriaan; van Dam, Nicole M; Conrath, Uwe

    2016-01-01

    Defense priming conditions diverse plant species for the superinduction of defense, often resulting in enhanced pest and disease resistance and abiotic stress tolerance. Here, we propose a guideline that might assist the plant research community in a consistent assessment of defense priming in

  17. Recognizing Plant Defense Priming.

    Science.gov (United States)

    Martinez-Medina, Ainhoa; Flors, Victor; Heil, Martin; Mauch-Mani, Brigitte; Pieterse, Corné M J; Pozo, Maria J; Ton, Jurriaan; van Dam, Nicole M; Conrath, Uwe

    2016-10-01

    Defense priming conditions diverse plant species for the superinduction of defense, often resulting in enhanced pest and disease resistance and abiotic stress tolerance. Here, we propose a guideline that might assist the plant research community in a consistent assessment of defense priming in plants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Building Numbers from Primes

    Science.gov (United States)

    Burkhart, Jerry

    2009-01-01

    Prime numbers are often described as the "building blocks" of natural numbers. This article shows how the author and his students took this idea literally by using prime factorizations to build numbers with blocks. In this activity, students explore many concepts of number theory, including the relationship between greatest common factors and…

  19. Recognizing plant defense priming

    NARCIS (Netherlands)

    Martinez-Medina, A.; Flors, V.; Heil, M.; Mauch-Mani, B.; Pieterse, C.M.J.; Pozo, M.J.; Ton, J.; Van Dam, N.M.; Conrath, U.

    2016-01-01

    Defense priming conditions diverse plant species for the superinduction of defense, often resulting in enhanced pest and disease resistance and abiotic stress tolerance. Here, we propose a guideline that might assist the plant research community in a consistent assessment of defense priming in

  20. Discovery: Prime Numbers

    Science.gov (United States)

    de Mestre, Neville

    2008-01-01

    Prime numbers are important as the building blocks for the set of all natural numbers, because prime factorisation is an important and useful property of all natural numbers. Students can discover them by using the method known as the Sieve of Eratosthenes, named after the Greek geographer and astronomer who lived from c. 276-194 BC. Eratosthenes…

  1. Monocyte chemoattractant protein-1 (MCP-1 regulates macrophage cytotoxicity in abdominal aortic aneurysm.

    Directory of Open Access Journals (Sweden)

    Qiwei Wang

    Full Text Available AIMS: In abdominal aortic aneurysm (AAA, macrophages are detected in the proximity of aortic smooth muscle cells (SMCs. We have previously demonstrated in a murine model of AAA that apoptotic SMCs attract monocytes and other leukocytes by producing MCP-1. Here we tested whether infiltrating macrophages also directly contribute to SMC apoptosis. METHODS AND RESULTS: Using a SMC/RAW264.7 macrophage co-culture system, we demonstrated that MCP-1-primed RAWs caused a significantly higher level of apoptosis in SMCs as compared to control macrophages. Next, we detected an enhanced Fas ligand (FasL mRNA level and membrane FasL protein expression in MCP-1-primed RAWs. Neutralizing FasL blocked SMC apoptosis in the co-culture. In situ proximity ligation assay showed that SMCs exposed to primed macrophages contained higher levels of receptor interacting protein-1 (RIP1/Caspase 8 containing cell death complexes. Silencing RIP1 conferred apoptosis resistance to SMCs. In the mouse elastase injury model of aneurysm, aneurysm induction increased the level of RIP1/Caspase 8 containing complexes in medial SMCs. Moreover, TUNEL-positive SMCs in aneurysmal tissues were frequently surrounded by CD68(+/FasL(+ macrophages. Conversely, elastase-treated arteries from MCP-1 knockout mice display a reduction of both macrophage infiltration and FasL expression, which was accompanied by diminished apoptosis of SMCs. CONCLUSION: Our data suggest that MCP-1-primed macrophages are more cytotoxic. MCP-1 appears to modulate macrophage cytotoxicity by increasing the level of membrane bound FasL. Thus, we showed that MCP-1-primed macrophages kill SMCs through a FasL/Fas-Caspase8-RIP1 mediated mechanism.

  2. Mechanisms of macrophage accumulation in the lungs of asbestos-exposed subjects

    International Nuclear Information System (INIS)

    Spurzem, J.R.; Saltini, C.; Rom, W.; Winchester, R.J.; Crystal, R.G.

    1987-01-01

    Chronic asbestos exposure is associated with the accumulation of mononuclear phagocytes in the lower respiratory tract. This process can be both protective and injurious, since macrophages can aid in asbestos clearance yet also modulate structural derangements of the alveolar walls. To understand why macrophages accumulate in the lungs of asbestos-exposed persons, 2 possible mechanisms were evaluated using alveolar macrophages from subjects with histories of chronic high exposure to airborne asbestos: enhanced recruitment of blood monocytes to the lung, and an increased rate of replication of macrophages in situ. Monoclonal antibody analysis with antibodies that detect surface antigens on the majority of circulating blood monocytes but only on a minority of mature alveolar macrophages demonstrated that an increased proportion of alveolar macrophages of asbestos workers expressed monocyte lineage antigens, suggesting the presence of young newly recruited macrophages and thus enhanced recruitment. Culture of the alveolar macrophages from these subjects with [ 3 H]thymidine followed by autoradiography demonstrated an increased proportion of alveolar macrophages synthesizing DNA, suggesting the macrophages are replicating at an increased rate in situ. These observations are consistent with the concept that both enhanced recruitment of blood monocytes and increased local proliferation of alveolar macrophages contribute to the accumulation mononuclear phagocytes in the lung of persons with chronic asbestos exposure

  3. Macrophage origin limits functional plasticity in helminth-bacterial co-infection.

    Directory of Open Access Journals (Sweden)

    Dominik Rückerl

    2017-03-01

    Full Text Available Rapid reprogramming of the macrophage activation phenotype is considered important in the defense against consecutive infection with diverse infectious agents. However, in the setting of persistent, chronic infection the functional importance of macrophage-intrinsic adaptation to changing environments vs. recruitment of new macrophages remains unclear. Here we show that resident peritoneal macrophages expanded by infection with the nematode Heligmosomoides polygyrus bakeri altered their activation phenotype in response to infection with Salmonella enterica ser. Typhimurium in vitro and in vivo. The nematode-expanded resident F4/80high macrophages efficiently upregulated bacterial induced effector molecules (e.g. MHC-II, NOS2 similarly to newly recruited monocyte-derived macrophages. Nonetheless, recruitment of blood monocyte-derived macrophages to Salmonella infection occurred with equal magnitude in co-infected animals and caused displacement of the nematode-expanded, tissue resident-derived macrophages from the peritoneal cavity. Global gene expression analysis revealed that although nematode-expanded resident F4/80high macrophages made an anti-bacterial response, this was muted as compared to newly recruited F4/80low macrophages. However, the F4/80high macrophages adopted unique functional characteristics that included enhanced neutrophil-stimulating chemokine production. Thus, our data provide important evidence that plastic adaptation of MΦ activation does occur in vivo, but that cellular plasticity is outweighed by functional capabilities specific to the tissue origin of the cell.

  4. Masked priming effect reflects evidence accumulated by the prime.

    Science.gov (United States)

    Kinoshita, Sachiko; Norris, Dennis

    2010-01-01

    In the same-different match task, masked priming is observed with the same responses but not different responses. Norris and Kinoshita's (2008) Bayesian reader account of masked priming explains this pattern based on the same principle as that explaining the absence of priming for nonwords in the lexical decision task. The pattern of priming follows from the way the model makes optimal decisions in the two tasks; priming does not depend on first activating the prime and then the target. An alternative explanation is in terms of a bias towards responding "same" that exactly counters the facilitatory effect of lexical access. The present study tested these two views by varying both the degree to which the prime predicts the response and the visibility of the prime. Unmasked primes produced effects expected from the view that priming is influenced by the degree to which the prime predicts the response. In contrast, with masked primes, the size of priming for the same response was completely unaffected by predictability. These results rule out response bias as an explanation of the absence of masked priming for different responses and, in turn, indicate that masked priming is not a consequence of automatic lexical access of the prime.

  5. Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Jaehong Kim

    2016-01-01

    Full Text Available Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.

  6. Multisensory Flavor Priming

    DEFF Research Database (Denmark)

    Dijksterhuis, Garmt Bernard

    2016-01-01

    with a taxonomy of different priming situations. In food-related applications of flavor, both bottom-up (sensory) as well as top-down (expectations) processes are at play. Most of the complex interactions that this leads to take place outside the awareness of the perceiving subject. A model is presented where...... many, past and current, aspects (sensory, surroundings, social, somatic, sentimental) of a (flavor) perception, together result in the perception of a flavor, its liking. or its choice. This model borrows on ideas from priming, situated/embodied cognition, and (food-related) perception.......Flavor is multisensory; several interacting sensory systems-taste, smell, and mouthfeel-together comprise "flavor," making it a cognitively constructed percept rather than a bottom-up sensory one. In this chapter, some of the complications this entails for flavor priming are introduced, along...

  7. Reexamining unconscious response priming: A liminal-prime paradigm.

    Science.gov (United States)

    Avneon, Maayan; Lamy, Dominique

    2018-03-01

    Research on the limits of unconscious processing typically relies on the subliminal-prime paradigm. However, this paradigm is limited in the issues it can address. Here, we examined the implications of using the liminal-prime paradigm, which allows comparing unconscious and conscious priming with constant stimulation. We adapted an iconic demonstration of unconscious response priming to the liminal-prime paradigm. On the one hand, temporal attention allocated to the prime and its relevance to the task increased the magnitude of response priming. On the other hand, the longer RTs associated with the dual task inherent to the paradigm resulted in response priming being underestimated, because unconscious priming effects were shorter-lived than conscious-priming effects. Nevertheless, when the impact of long RTs was alleviated by considering the fastest trials or by imposing a response deadline, conscious response priming remained considerably larger than unconscious response priming. These findings suggest that conscious perception strongly modulates response priming. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Soluble ICAM-1 activates lung macrophages and enhances lung injury

    DEFF Research Database (Denmark)

    Schmal, H; Czermak, B J; Lentsch, A B

    1998-01-01

    production of TNF-alpha and the CXC chemokine, macrophage inflammatory protein-2 (MIP-2). Alveolar macrophages exhibited cytokine responses to both sICAM-1 and immobilized sICAM-1, while rat PBMCs failed to demonstrate similar responses. Exposure of alveolar macrophages to sICAM-1 resulted in NFkappa......B activation (which was blocked by the presence of the aldehyde peptide inhibitor of 28S proteosome and by genistein, a tyrosine kinase inhibitor). As expected, cross-linking of CD18 on macrophages with Ab resulted in generation of TNF-alpha and MIP-2. This response was also inhibited in the presence...... of TNF-alpha and MIP-2 and increased neutrophil recruitment. Therefore, through engagement of beta2 integrins, sICAM-1 enhances alveolar macrophage production of MIP-2 and TNF-alpha, the result of which is intensified lung injury after intrapulmonary disposition of immune complexes....

  9. Macrophage Functions in Early Dissemination and Dormancy of Breast Cancer

    Science.gov (United States)

    2016-09-01

    mammary gland development 17,18, 69   arguing that normal mammary epithelial cells cooperate with these innate immune cells 70   for invasive... cells lacking 218     11   lymphoid and granulocytic markers (Supplementary Fig.3B). viSNE plots 30 of myelo-219   monocytic cells (Fig.5A...macrophages are actively recruited by pre-malignant ErbB2 overexpressing cancer cells and that these intra-epithelial macrophages then produce factors

  10. Macrophages in synovial inflammation

    Directory of Open Access Journals (Sweden)

    Aisling eKennedy

    2011-10-01

    Full Text Available AbstractSynovial macrophages are one of the resident cell types in synovial tissue and while they remain relatively quiescent in the healthy joint, they become activated in the inflamed joint and, along with infiltrating monocytes/macrophages, regulate secretion of pro-inflammatory cytokines and enzymes involved in driving the inflammatory response and joint destruction. Synovial macrophages are positioned throughout the sub-lining layer and lining layer at the cartilage-pannus junction and mediate articular destruction. Sub-lining macrophages are now also considered as the most reliable biomarker for disease severity and response to therapy in rheumatoid arthritis (RA. There is a growing understanding of the molecular drivers of inflammation and an appreciation that the resolution of inflammation is an active process rather than a passive return to homeostasis, and this has implications for our understanding of the role of macrophages in inflammation. Macrophage phenotype determines the cytokine secretion profile and tissue destruction capabilities of these cells. Whereas inflammatory synovial macrophages have not yet been classified into one phenotype or another it is widely known that TNFα and IL-l, characteristically released by M1 macrophages, are abundant in RA while IL-10 activity, characteristic of M2 macrophages, is somewhat diminished.Here we will briefly review our current understanding of macrophages and macrophage polarisation in RA as well as the elements implicated in controlling polarisation, such as cytokines and transcription factors like NFκB, IRFs and NR4A, and pro-resolving factors, such as LXA4 and other lipid mediators which may promote a non-inflammatory, pro-resolving phenotype and may represent a novel therapeutic paradigm.

  11. PrimeFaces blueprints

    CERN Document Server

    Jonna, Sudheer

    2014-01-01

    If you are a Java developer with experience of frontend UI development, and want to take the plunge to develop stunning UI applications with the most popular JSF framework, PrimeFaces, then this book is for you. For those with entrepreneurial aspirations, this book will provide valuable insights into how to utilize successful business models.

  12. Macrophage heterogeneity in tissues: phenotypic diversity and functions

    Science.gov (United States)

    Gordon, Siamon; Plüddemann, Annette; Martinez Estrada, Fernando

    2014-01-01

    During development and throughout adult life, macrophages derived from hematopoietic progenitors are seeded throughout the body, initially in the absence of inflammatory and infectious stimuli as tissue-resident cells, with enhanced recruitment, activation, and local proliferation following injury and pathologic insults. We have learned a great deal about macrophage properties ex vivo and in cell culture, but their phenotypic heterogeneity within different tissue microenvironments remains poorly characterized, although it contributes significantly to maintaining local and systemic homeostasis, pathogenesis, and possible treatment. In this review, we summarize the nature, functions, and interactions of tissue macrophage populations within their microenvironment and suggest questions for further investigation. PMID:25319326

  13. Superficial Priming in Episodic Recognition

    Science.gov (United States)

    Dopkins, Stephen; Sargent, Jesse; Ngo, Catherine T.

    2010-01-01

    We explored the effect of superficial priming in episodic recognition and found it to be different from the effect of semantic priming in episodic recognition. Participants made recognition judgments to pairs of items, with each pair consisting of a prime item and a test item. Correct positive responses to the test item were impeded if the prime…

  14. [Macrophages in human semen].

    Science.gov (United States)

    Bouvet, Beatriz Reina; Brufman, Adriana Silvia; Paparella, Cecilia Vicenta; Feldman, Rodolfo Nestor; Gatti, Vanda Nora; Solis, Edita Amalia

    2003-11-01

    To investigate the presence of macrophages in human semen samples and the function they carry out in the seminal fluid. Their presence was studied in relation to spermatic morphology, percentage of spermatozoids with native DNA, and presence of antispermatic antibodies. The work was performed with semen samples from 31 unfertile males from 63 couples in which the "female factor" was ruled out as the cause of infertility. Sperm study according to WHO (1992) was carried out in all samples, in addition to: DNA study with acridine orange as fluorocrom, macrophage concentration by neutral red in a Neubauer camera, and detection of antispermatic antibodies with a mixed agglutination test (TAC II) (validated with Mar Screen-Fertility technologies). Sperm morphology was evaluated by Papanicolaou test. 19/31 selected sperm samples (61.3%) showed increased concentration of macrophages, 13 of them (41.9%) with denaturalized DNA, and 8 (25.8%) abnormal morphology. Six samples showed increased macrophage concentration and predominance of native DNA, whereas 11 samples showed increased macrophages and abnormal morphology. Among 18 (58.1%) samples showing antispermatic antibodies 14 (77.7%) had an increased concentration of macrophages. Statistical analysis resulted in a high correlation between macrophage concentration and increased percentage of spermatozoids with denaturalized DNA (p < 0.05). An increased concentration of macrophages is associated with the presence of antispermatic antibodies (p < 0.05). There was not evidence of significant association between concentration of macrophages and percentage of morphologically normal spermatozoids (p < 0.05). We can conclude that macrophages are present in human semen and participate in immunovigilance contributing to improve the seminal quality.

  15. Subliminal semantic priming in speech.

    Directory of Open Access Journals (Sweden)

    Jérôme Daltrozzo

    Full Text Available Numerous studies have reported subliminal repetition and semantic priming in the visual modality. We transferred this paradigm to the auditory modality. Prime awareness was manipulated by a reduction of sound intensity level. Uncategorized prime words (according to a post-test were followed by semantically related, unrelated, or repeated target words (presented without intensity reduction and participants performed a lexical decision task (LDT. Participants with slower reaction times in the LDT showed semantic priming (faster reaction times for semantically related compared to unrelated targets and negative repetition priming (slower reaction times for repeated compared to semantically related targets. This is the first report of semantic priming in the auditory modality without conscious categorization of the prime.

  16. Accumulation of M1-like macrophages in type 2 diabetic islets is followed by a systemic shift in macrophage polarization.

    Science.gov (United States)

    Cucak, Helena; Grunnet, Lars Groth; Rosendahl, Alexander

    2014-01-01

    Human T2D is characterized by a low-grade systemic inflammation, loss of β-cells, and diminished insulin production. Local islet immunity is still poorly understood, and hence, we evaluated macrophage subpopulations in pancreatic islets in the well-established murine model of T2D, the db/db mouse. Already at 8 weeks of disease, on average, 12 macrophages were observed in the diabetic islets, whereas only two were recorded in the nondiabetic littermates. On a detailed level, the islet resident macrophages increased fourfold compared with nondiabetic littermates, whereas a pronounced recruitment (eightfold) of a novel subset of macrophages (CD68+F4/80-) was observed. The majority of the CD68+F4/80+ but only 40% of the CD68+F4/80- islet macrophages expressed CD11b. Both islet-derived macrophage subsets expressed moderate MHC-II, high galectin-3, and low CD80/CD86 levels, suggesting the cells to be macrophages rather than DCs. On a functional level, the vast majority of the macrophages in the diabetic islets was of the proinflammatory, M1-like phenotype. The systemic immunity in diabetic animals was characterized by a low-grade inflammation with elevated cytokine levels and increase of splenic cytokine, producing CD68+F4/80- macrophages. In late-stage diabetes, the cytokine signature changed toward a TGF-β-dominated profile, coinciding with a significant increase of galectin-3-positive macrophages in the spleen. In summary, our results show that proinflammatory M1-like galectin-3+ CD80/CD86(low) macrophages invade diabetic islets. Moreover, the innate immunity matures in a diabetes-dependent manner from an initial proinflammatory toward a profibrotic phenotype, supporting the concept that T2D is an inflammatory disease.

  17. Conditioned medium from alternatively activated macrophages induce mesangial cell apoptosis via the effect of Fas

    International Nuclear Information System (INIS)

    Huang, Yuan; Luo, Fangjun; Li, Hui; Jiang, Tao; Zhang, Nong

    2013-01-01

    During inflammation in the glomerulus, the proliferation of myofiroblast-like mesangial cells is commonly associated with the pathological process. Macrophages play an important role in regulating the growth of resident mesangial cells in the glomeruli. Alternatively activated macrophage (M2 macrophage) is a subset of macrophages induced by IL-13/IL-4, which is shown to play a repair role in glomerulonephritis. Prompted by studies of development, we performed bone marrow derived macrophage and rat mesangial cell co-culture study. Conditioned medium from IL-4 primed M2 macrophages induced rat mesangial cell apoptosis. The pro-apoptotic effect of M2 macrophages was demonstrated by condensed nuclei stained with Hoechst 33258, increased apoptosis rates by flow cytometry analysis and enhanced caspase-3 activation by western blot. Fas protein was up-regulated in rat mesangial cells, and its neutralizing antibody ZB4 partly inhibited M2 macrophage-induced apoptosis. The up-regulated arginase-1 expression in M2 macrophage also contributed to this apoptotic effect. These results indicated that the process of apoptosis triggered by conditioned medium from M2 macrophages, at least is partly conducted through Fas in rat mesangial cells. Our findings provide compelling evidence that M2 macrophages control the growth of mesangial cells in renal inflammatory conditions. - Highlights: • Conditioned-medium from M2 macrophages induces rat mesangial cell (MsC) apoptosis. • M2 macrophage conditioned medium exerts its pro-apoptotic effects via Fas ligand. • Arginase-1 activity in M2 macrophages plays a role in inducing apoptosis in rat MsC

  18. Conditioned medium from alternatively activated macrophages induce mesangial cell apoptosis via the effect of Fas

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Yuan; Luo, Fangjun; Li, Hui; Jiang, Tao; Zhang, Nong, E-mail: nzhang@fudan.edu.cn

    2013-11-15

    During inflammation in the glomerulus, the proliferation of myofiroblast-like mesangial cells is commonly associated with the pathological process. Macrophages play an important role in regulating the growth of resident mesangial cells in the glomeruli. Alternatively activated macrophage (M2 macrophage) is a subset of macrophages induced by IL-13/IL-4, which is shown to play a repair role in glomerulonephritis. Prompted by studies of development, we performed bone marrow derived macrophage and rat mesangial cell co-culture study. Conditioned medium from IL-4 primed M2 macrophages induced rat mesangial cell apoptosis. The pro-apoptotic effect of M2 macrophages was demonstrated by condensed nuclei stained with Hoechst 33258, increased apoptosis rates by flow cytometry analysis and enhanced caspase-3 activation by western blot. Fas protein was up-regulated in rat mesangial cells, and its neutralizing antibody ZB4 partly inhibited M2 macrophage-induced apoptosis. The up-regulated arginase-1 expression in M2 macrophage also contributed to this apoptotic effect. These results indicated that the process of apoptosis triggered by conditioned medium from M2 macrophages, at least is partly conducted through Fas in rat mesangial cells. Our findings provide compelling evidence that M2 macrophages control the growth of mesangial cells in renal inflammatory conditions. - Highlights: • Conditioned-medium from M2 macrophages induces rat mesangial cell (MsC) apoptosis. • M2 macrophage conditioned medium exerts its pro-apoptotic effects via Fas ligand. • Arginase-1 activity in M2 macrophages plays a role in inducing apoptosis in rat MsC.

  19. Depletion of resident macrophages does not alter sensory regeneration in the avian cochlea.

    Directory of Open Access Journals (Sweden)

    Mark E Warchol

    Full Text Available Macrophages are the primary effector cells of the innate immune system and are also activated in response to tissue injury. The avian cochlea contains a population of resident macrophages, but the precise function of those cells is not known. The present study characterized the behavior of cochlear macrophages after aminoglycoside ototoxicity and also examined the possible role of macrophages in sensory regeneration. We found that the undamaged chick cochlea contains a large resting population of macrophages that reside in the hyaline cell region, immediately outside the abneural (inferior border of the sensory epithelium. Following ototoxic injury, macrophages appear to migrate out of the hyaline cell region and towards the basilar membrane, congregating immediately below the lesioned sensory epithelium. In order to determine whether recruited macrophages contribute to the regeneration of sensory receptors, we quantified supporting cell proliferation and hair cell recovery after the elimination of most resident macrophages via application of liposomally-encapsulated clodronate. Examination of macrophage-depleted specimens at two days following ototoxic injury revealed no deficits in hair cell clearance, when compared to normal controls. In addition, we found that elimination of macrophages did not affect either regenerative proliferation of supporting cells or the production of replacement hair cells. However, we did find that macrophage-depleted cochleae contained reduced numbers of proliferative mesothelial cells below the basilar membrane. Our data suggest that macrophages are not required for normal debris clearance and regeneration, but that they may play a role in the maintenance of the basilar membrane.

  20. Hyper-inflammation and skin destruction mediated by rosiglitazone activation of macrophages in IL-6 deficiency

    DEFF Research Database (Denmark)

    Das, Lopa M; Rosenjack, Julie; Au, Liemin

    2015-01-01

    Injury initiates recruitment of macrophages to support tissue repair; however, excessive macrophage activity may exacerbate tissue damage causing further destruction and subsequent delay in wound repair. Here we show that the peroxisome proliferation-activated receptor-γ agonist, rosiglitazone (R...

  1. Macrophage Populations in Visceral Adipose Tissue from Pregnant Women: Potential Role of Obesity in Maternal Inflammation

    Directory of Open Access Journals (Sweden)

    Eyerahi Bravo-Flores

    2018-04-01

    Full Text Available Obesity is associated with inflammatory changes and accumulation and phenotype polarization of adipose tissue macrophages (ATMs. Obese pregnant women have alterations in adipose tissue composition, but a detailed description of macrophage population is not available. In this study, we characterized macrophage populations in visceral adipose tissue (VAT from pregnant women with normal, overweight, and obese pregestational weight. Immunophenotyping of macrophages from VAT biopsies was performed by flow cytometry using CD45 and CD14 as markers of hematopoietic and monocyte linage, respectively, while HLA-DR, CD11c, CD163, and CD206 were used as pro- and anti-inflammatory markers. Adipocyte number and size were evaluated by light microscopy. The results show that pregnant women that were overweight and obese during the pregestational period had adipocyte hypertrophy. Two different macrophage populations in VAT were identified: recruited macrophages (CD45+CD14+, and a novel population lacking CD45, which was considered to be a resident macrophages subset (CD45−CD14+. The number of resident HLA−DRlow/− macrophages showed a negative correlation with body mass index (BMI. Both resident and recruited macrophages from obese women expressed higher CD206 levels. CD11c expression was higher in resident HLA-DR+ macrophages from obese women. A strong correlation between CD206 and CD11c markers and BMI was observed. Our findings show that being overweight and obese in the pregestational period is associated with adipocyte hypertrophy and specific ATMs populations in VAT.

  2. The elusive antifibrotic macrophage

    Directory of Open Access Journals (Sweden)

    Adhyatmika eAdhyatmika

    2015-11-01

    Full Text Available Fibrotic diseases, especially of the liver, the cardiovascular system, the kidneys, and the lungs account for approximately 45% of deaths in Western societies. Fibrosis is a serious complication associated with aging and/or chronic inflammation or injury and cannot be treated effectively yet. It is characterized by excessive deposition of extracellular matrix (ECM proteins by myofibroblasts and impaired degradation by macrophages. This ultimately destroys the normal structure of an organ, which leads to loss of function. Most efforts to develop drugs have focused on inhibiting ECM production by myofibroblasts and have not yielded many effective drugs yet. Another option is to stimulate the cells that are responsible for degradation and uptake of excess ECM, i.e. antifibrotic macrophages. However, macrophages are plastic cells that have many faces in fibrosis, including profibrotic behaviour stimulating ECM production. This can be dependent on their origin, as the different organs have tissue-resident macrophages with different origins and a various influx of incoming monocytes in steady-state conditions and during fibrosis. To be able to pharmacologically stimulate the right kind of behaviour in fibrosis, a thorough characterization of antifibrotic macrophages is necessary, as well as an understanding of the signals they need to degrade ECM. In this review we will summarize the current state of the art regarding the antifibrotic macrophage phenotype and the signals that stimulate its behaviour.

  3. Past Their Prime

    OpenAIRE

    Friedman, Rebecca E

    2012-01-01

    Past Their Prime is a half-hour documentary about Colo— the oldest living gorilla in captivity — on her 55th birthday, and her place in the world of geriatric zoo animal care.                It’s winter at the Columbus Zoo in Columbus, Ohio. In the ape house elderly visitors browse slowly, wrapped in down jackets. Children run from exhibit to exhibit, pointing at the animals they see and announcing each one to their grandparents. Behind the glass, Colo, the...

  4. The Upregulation of Integrin αDβ2 (CD11d/CD18) on Inflammatory Macrophages Promotes Macrophage Retention in Vascular Lesions and Development of Atherosclerosis.

    Science.gov (United States)

    Aziz, Moammir H; Cui, Kui; Das, Mitali; Brown, Kathleen E; Ardell, Christopher L; Febbraio, Maria; Pluskota, Elzbieta; Han, Juying; Wu, Huaizhu; Ballantyne, Christie M; Smith, Jonathan D; Cathcart, Martha K; Yakubenko, Valentin P

    2017-06-15

    Macrophage accumulation is a critical step during development of chronic inflammation, initiating progression of many devastating diseases. Leukocyte-specific integrin α D β 2 (CD11d/CD18) is dramatically upregulated on macrophages at inflammatory sites. Previously we found that CD11d overexpression on cell surfaces inhibits in vitro cell migration due to excessive adhesion. In this study, we have investigated how inflammation-mediated CD11d upregulation contributes to macrophage retention at inflammatory sites during atherogenesis. Atherosclerosis was evaluated in CD11d -/- /ApoE -/- mice after 16 wk on a Western diet. CD11d deficiency led to a marked reduction in lipid deposition in aortas and isolated macrophages. Macrophage numbers in aortic sinuses of CD11d -/- mice were reduced without affecting their apoptosis and proliferation. Adoptive transfer of fluorescently labeled wild-type and CD11d -/- monocytes into ApoE -/- mice demonstrated similar recruitment from circulation, but reduced accumulation of CD11d -/- macrophages within the aortas. Furthermore, CD11d expression was significantly upregulated on macrophages in atherosclerotic lesions and M1 macrophages in vitro. Interestingly, expression of the related ligand-sharing integrin CD11b was not altered. This difference defines their distinct roles in the regulation of macrophage migration. CD11d-deficient M1 macrophages demonstrated improved migration in a three-dimensional fibrin matrix and during resolution of peritoneal inflammation, whereas migration of CD11b -/- M1 macrophages was not affected. These results prove the contribution of high densities of CD11d to macrophage arrest during atherogenesis. Because high expression of CD11d was detected in several inflammation-dependent diseases, we suggest that CD11d/CD18 upregulation on proinflammatory macrophages may represent a common mechanism for macrophage retention at inflammatory sites, thereby promoting chronic inflammation and disease development

  5. Multiple Myeloma Macrophages: Pivotal Players in the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Simona Berardi

    2013-01-01

    Full Text Available Tumor microenvironment is essential for multiple myeloma (MM growth, progression, and drug resistance through provision of survival signals and secretion of growth and proangiogenic factors. This paper examines the importance of macrophages within MM bone marrow (BM microenvironment, referred to as MM-associated macrophages, as a potential niche component that supports tumor plasma cells. These macrophages are derived from peripheral blood monocytes recruited into the tumor. Upon activation by MM plasma cells and mesenchymal stromal cells, macrophages can release growth factors, proteolytic enzymes, cytokines, and inflammatory mediators that promote plasma cell growth and survival. Macrophages promote tumor progression through several mechanisms including angiogenesis, growth, and drug resistance. Indeed, these macrophages are essential for the induction of an angiogenic response through vasculogenic mimicry, and this ability proceeds in step with progression of the plasma cell tumors. Data suggest that macrophages play an important role in the biology and survival of patients with MM, and they may be a target for the MM antivascular management.

  6. Prime time sexual harassment.

    Science.gov (United States)

    Grauerholz, E; King, A

    1997-04-01

    This study explores the explicit and implicit messages of sexual harassment that viewers receive when viewing prime-time television in the US. A content analysis of 48 hours of prime-time television reveals that sexual harassment on television is both highly visible and invisible. Sexual harassment is rendered visible simply by its prominence in these programs. Incidents involving quid-pro-quo harassment and environmental harassment occur with regularity on television. Furthermore, about 84% of the shows studied contained at least one incident of sexual harassment; yet these acts of sexual harassment remained largely invisible because none of the behaviors were labeled as sexual harassment. These incidents are presented in humorous ways, and victims are generally unharmed and very effective at ending the harassment. Although such programs may actually reflect the reality of many women's lives in terms of prevalence of sexual harassment, they perpetuate several myths about sexual harassment, such as that sexual harassment is not serious and that victims should be able to handle the situations themselves.

  7. Transposed-Letter Priming Effects with Masked Subset Primes: A Re-Examination of the "Relative Position Priming Constraint"

    Science.gov (United States)

    Stinchcombe, Eric J.; Lupker, Stephen J.; Davis, Colin J.

    2012-01-01

    Three experiments are reported investigating the role of letter order in orthographic subset priming (e.g., "grdn"-GARDEN) using both the conventional masked priming technique as well as the sandwich priming technique in a lexical decision task. In all three experiments, subset primes produced priming with the effect being considerably…

  8. Primes, Geometry and Condensed Matter

    Directory of Open Access Journals (Sweden)

    Al Rabeh R. H.

    2009-07-01

    Full Text Available Fascination with primes dates back to the Greeks and before. Primes are named by some "the elementary particles of arithmetic" as every nonprime integer is made of a unique set of primes. In this article we point to new connections between primes, geometry and physics which show that primes could be called "the elementary particles of physics" too. This study considers the problem of closely packing similar circles/spheres in 2D/3D space. This is in effect a discretization process of space and the allowable number in a pack is found to lead to some unexpected cases of prime configurations which is independent of the size of the constituents. We next suggest that a non-prime can be considered geometrically as a symmetric collection that is separable (factorable into similar parts- six is two threes or three twos for example. A collection that has no such symmetry is a prime. As a result, a physical prime aggregate is more difficult to split symmetrically resulting in an inherent stability. This "number/physical" stability idea applies to bigger collections made from smaller (prime units leading to larger stable prime structures in a limitless scaling up process. The distribution of primes among numbers can be understood better using the packing ideas described here and we further suggest that differing numbers (and values of distinct prime factors making a nonprime collection is an important factor in determining the probability and method of possible and subsequent disintegration. Disintegration is bound by energy conservation and is closely related to symmetry by Noether theorems. Thinking of condensed matter as the packing of identical elements, we examine plots of the masses of chemical elements of the periodic table, and also those of the elementary particles of physics, and show that prime packing rules seem to play a role in the make up of matter. The plots show convincingly that the growth of prime numbers and that of the masses of

  9. Primes, Geometry and Condensed Matter

    Directory of Open Access Journals (Sweden)

    Al Rabeh R. H.

    2009-07-01

    Full Text Available Fascination with primes dates back to the Greeks and before. Primes are named by some “the elementary particles of arithmetic” as every nonprime integer is made of a unique set of primes. In this article we point to new connections between primes, geometry and physics which show that primes could be called “the elementary particles of physics” too. This study considers the problem of closely packing similar circles / spheres in 2D / 3D space. This is in effect a discretization process of space and the allowable num- ber in a pack is found to lead to some unexpected cases of prime configurations which is independent of the size of the constituents. We next suggest that a non-prime can be considered geometrically as a symmetric collection that is separable (factorable into similar parts- six is two threes or three twos for example. A collection that has no such symmetry is a prime. As a result, a physical prime aggregate is more difficult to split symmetrically resulting in an inherent stability. This “number / physical” stability idea applies to bigger collections made from smaller (prime units leading to larger sta- ble prime structures in a limitless scaling up process. The distribution of primes among numbers can be understood better using the packing ideas described here and we further suggest that differing numbers (and values of distinct prime factors making a nonprime collection is an important factor in determining the probability and method of possible and subsequent disintegration. Disintegration is bound by energy conservation and is closely related to symmetry by Noether theorems. Thinking of condensed matter as the packing of identical elements, we examine plots of the masses of chemical elements of the periodic table, and also those of the elementary particles of physics, and show that prime packing rules seem to play a role in the make up of matter. The plots show con- vincingly that the growth of prime numbers and that

  10. Sequential experiments with primes

    CERN Document Server

    Caragiu, Mihai

    2017-01-01

    With a specific focus on the mathematical life in small undergraduate colleges, this book presents a variety of elementary number theory insights involving sequences largely built from prime numbers and contingent number-theoretic functions. Chapters include new mathematical ideas and open problems, some of which are proved in the text. Vector valued MGPF sequences, extensions of Conway’s Subprime Fibonacci sequences, and linear complexity of bit streams derived from GPF sequences are among the topics covered in this book. This book is perfect for the pure-mathematics-minded educator in a small undergraduate college as well as graduate students and advanced undergraduate students looking for a significant high-impact learning experience in mathematics.

  11. Rhizosphere priming: a nutrient perspective

    Directory of Open Access Journals (Sweden)

    Feike Auke Dijkstra

    2013-07-01

    Full Text Available Rhizosphere priming is the change in decomposition of soil organic matter (SOM caused by root activity. Rhizosphere priming plays a crucial role in soil carbon (C dynamics and their response to global climate change. Rhizosphere priming may be affected by soil nutrient availability, but rhizosphere priming itself can also affect nutrient supply to plants. These interactive effects may be of particular relevance in understanding the sustained increase in plant growth and nutrient supply in response to a rise in atmospheric CO2 concentration. We examined how these interactions were affected by elevated CO2 in two similar semiarid grassland field studies. We found that an increase in rhizosphere priming enhanced the release of nitrogen (N through decomposition of a larger fraction of SOM in one study, but not in the other. We postulate that rhizosphere priming may enhance N supply to plants in systems that are N limited, but that rhizosphere priming may not occur in systems that are phosphorus (P limited. Under P limitation, rhizodeposition may be used for mobilisation of P, rather than for decomposition of SOM. Therefore, with increasing atmospheric CO2 concentrations, rhizosphere priming may play a larger role in affecting C sequestration in N poor than in P poor soils.

  12. Continued Funding for Prime Development

    Science.gov (United States)

    2012-04-18

    PHP language with the help of CMF Drupal-6. The standard modules of the Drupal core set are developed by third parties and obtained from the...repository drupal.org. Part of the modules was modified specifically for the PrIMe portal. The PrIMe portal uses MySQL for the database technology. It is

  13. Mechanisms of subliminal response priming.

    Science.gov (United States)

    Kiesel, Andrea; Kunde, Wilfried; Hoffmann, Joachim

    2008-07-15

    Subliminal response priming has been considered to operate on several stages, e.g. perceptual, central or motor stages might be affected. While primes' impact on target perception has been clearly demonstrated, semantic response priming recently has been thrown into doubt (e.g. Klinger, Burton, & Pitts, 2000). Finally, LRP studies have revealed that subliminal primes evoke motor processes. Yet, the premises for such prime-evoked motor activation are not settled. A transfer of priming to stimuli that have never been presented as targets appears particularly interesting because it suggests a level of processing that goes beyond a reactivation of previously acquired S-R links. Yet, such transfer has not always withstood empirical testing. To account for these contradictory results, we proposed a two-process model (Kunde, Kiesel, & Hoffmann, 2003): First, participants build up expectations regarding imperative stimuli for the required responses according to experience and/or instructions. Second, stimuli that match these "action triggers" directly activate the corresponding motor responses irrespective of their conscious identification. In line with these assumptions, recent studies revealed that non-target primes induce priming when they fit the current task intentions and when they are expected in the experimental setting.

  14. MPQS with three large primes

    NARCIS (Netherlands)

    Leyland, P.; Lenstra, A.K.; Dodson, B.; Muffett, A.; Wagstaff, S.; Fieker, C.; Kohel, D.R.

    2002-01-01

    We report the factorization of a 135-digit integer by the triple-large-prime variation of the multiple polynomial quadratic sieve. Previous workers [6][10] had suggested that using more than two large primes would be counterproductive, because of the greatly increased number of false reports from

  15. PrimeFaces beginner's guide

    CERN Document Server

    Reddy, K Siva Prasad

    2013-01-01

    A guide for beginner's with step-by-step instructions and an easy-to-follow approach.PrimeFaces Beginners Guide is a simple and effective guide for beginners, wanting to learn and implement PrimeFaces in their JSF-based applications. Some basic JSF and jQuery skills are required before you start working through the book.

  16. Cell Elasticity Determines Macrophage Function

    Science.gov (United States)

    Patel, Naimish R.; Bole, Medhavi; Chen, Cheng; Hardin, Charles C.; Kho, Alvin T.; Mih, Justin; Deng, Linhong; Butler, James; Tschumperlin, Daniel; Fredberg, Jeffrey J.; Krishnan, Ramaswamy; Koziel, Henry

    2012-01-01

    Macrophages serve to maintain organ homeostasis in response to challenges from injury, inflammation, malignancy, particulate exposure, or infection. Until now, receptor ligation has been understood as being the central mechanism that regulates macrophage function. Using macrophages of different origins and species, we report that macrophage elasticity is a major determinant of innate macrophage function. Macrophage elasticity is modulated not only by classical biologic activators such as LPS and IFN-γ, but to an equal extent by substrate rigidity and substrate stretch. Macrophage elasticity is dependent upon actin polymerization and small rhoGTPase activation, but functional effects of elasticity are not predicted by examination of gene expression profiles alone. Taken together, these data demonstrate an unanticipated role for cell elasticity as a common pathway by which mechanical and biologic factors determine macrophage function. PMID:23028423

  17. Cell elasticity determines macrophage function.

    Directory of Open Access Journals (Sweden)

    Naimish R Patel

    Full Text Available Macrophages serve to maintain organ homeostasis in response to challenges from injury, inflammation, malignancy, particulate exposure, or infection. Until now, receptor ligation has been understood as being the central mechanism that regulates macrophage function. Using macrophages of different origins and species, we report that macrophage elasticity is a major determinant of innate macrophage function. Macrophage elasticity is modulated not only by classical biologic activators such as LPS and IFN-γ, but to an equal extent by substrate rigidity and substrate stretch. Macrophage elasticity is dependent upon actin polymerization and small rhoGTPase activation, but functional effects of elasticity are not predicted by examination of gene expression profiles alone. Taken together, these data demonstrate an unanticipated role for cell elasticity as a common pathway by which mechanical and biologic factors determine macrophage function.

  18. Priming semantico e museografia / Semantic priming and museography

    Directory of Open Access Journals (Sweden)

    Annalisa Banzi

    2012-05-01

    Full Text Available Il priming è una tipologia di memoria implicita che facilita l’apprendimento di stimoli di diversa natura (stimoli visivi, semantici, etc.. Un allestimento museale che adotti strumenti basati sul priming potrebbe aiutare il pubblico a selezionare i contenuti relativi agli oggetti esposti. In questo articolo viene descritta l’applicazione del priming semantico allo spazio museale. Questa operazione in prima battutta potrebbe essere letta come una mancanza di fiducia nelle capacità cognitive del visitatore nel discriminare il significato delle informazioni. In realtà è una forma di sostegno per aiutare il visitatore a sviluppare gradualmente una propria metodologia di approccio ai contenuti proposti nel museo. Grazie al priming, il pubblico riceve una serie di stimoli che possono aiutare a costituire la base delle proprie conoscenze in ambito storico-artistico ed essere il punto di partenza sul quale costruire un metodo critico.   Many psychological aspects such as motivation, emotion, and attention, affect human learning. Among these, priming triggers and tunes implicit memory processes. Hence the goal of this paper is to check whether semantic priming can be used as an effective tool to design a supportive museum environment where people can easily learn. Moreover, the resulting stronger and more persistent memories could encourage museum visitors to learn more and better, and to develop a method to “read” the artworks. After a brief overview of current models of semantic priming, practical and theoretical issues are considered and discussed.

  19. The Prime Numbers Hidden Symmetric Structure and its Relation to the Twin Prime Infinitude and an Improved Prime Number Theorem

    CERN Document Server

    Mikoss, I

    2006-01-01

    Due to the sieving process represented by a Secondary Sieving Map; during the generation of the prime numbers, geometric structures with definite symmetries are formed which become evident through their geometrical representations. The study of these structures allows the development of a constructive prime generating formula. This defines a mean prime density yielding a second order recursive and discrete prime producing formula and a second order differential equation whose solutions produce an improved Prime Number Theorem. Applying these results to twin prime pairs is possible to generate a Twin Prime Number Theorem and important conclusions about the infinitude of the twin primes.

  20. The Alveolar Microenvironment of Patients Infected with Human Immunodeficiency Virus Does Not Modify Alveolar Macrophage Interactions with Streptococcus pneumoniae

    Science.gov (United States)

    Jagoe, R. Thomas; Jarman, Elizabeth R.; North, James C.; Pridmore, Alison; Musaya, Janelisa; French, Neil; Zijlstra, Eduard E.; Molyneux, Malcolm E.; Read, Robert C.

    2013-01-01

    We tested the hypothesis that HIV infection results in activation of alveolar macrophages and that this might be associated with impaired defense against pneumococcus. We compared alveolar macrophages and lymphocytes in 131 bronchoalveolar lavage samples from HIV-infected and healthy controls using inflammatory gene microarrays, flow cytometry, real-time PCR, and enzyme-linked immunosorbent assay (ELISA) to determine the pattern of macrophage activation associated with HIV infection and the effect of this activation on defense against pneumococcus. We used gamma interferon (IFN-γ) priming to mimic the cellular milieu in HIV-infected lungs. InnateDB and BioLayout 3D were used to analyze the interactions of the upregulated genes. Alveolar macrophages from HIV-infected adults showed increased gene expression and cytokine production in a classical pattern. Bronchoalveolar lavage from HIV-infected subjects showed excess CD8+ lymphocytes with activated phenotype. Toll-like receptor 4 (TLR4) expression was increased in macrophages from HIV-infected subjects, but function was similar between the groups; lung lavage fluid did not inhibit TLR function in transfected HeLa cells. Alveolar macrophages from HIV-infected subjects showed normal binding and internalization of opsonized pneumococci, with or without IFN-γ priming. Alveolar macrophages from HIV-infected subjects showed classical activation compared to that of healthy controls, but this does not alter macrophage interactions with pneumococci. PMID:23576675

  1. Co-expression of HIV-1 virus-like particles and granulocyte-macrophage colony stimulating factor by GEO-D03 DNA vaccine

    Science.gov (United States)

    Hellerstein, Michael; Xu, Yongxian; Marino, Tracie; Lu, Shan; Yi, Hong; Wright, Elizabeth R.; Robinson, Harriet L.

    2012-01-01

    Here, we report on GEO-D03, a DNA vaccine that co-expresses non-infectious HIV-1 virus-like particles (VLPs) and the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). The virus-like particles display the native gp160 form of the HIV-1 Envelope glycoprotein (Env) and are designed to elicit antibody against the natural form of Env on virus and virus-infected cells. The DNA-expressed HIV Gag, Pol and Env proteins also have the potential to elicit virus-specific CD4 and CD8 T cells. The purpose of the co-expressed GM-CSF is to target a cytokine that recruits, expands and differentiates macrophages and dendritic cells to the site of VLP expression. The GEO-D03 DNA vaccine is currently entered into human trials as a prime for a recombinant modified vaccinia Ankara (MVA) boost. In preclinical studies in macaques using an SIV prototype vaccine, this vaccination regimen elicited both anti-viral T cells and antibody, and provided 70% protection against acquisition during 12 weekly rectal exposures with a heterologous SIV. Higher avidity of the Env-specific Ab for the native form of the Env in the challenge virus correlated with lower likelihood of SIV infection. PMID:23111169

  2. Network topologies and dynamics leading to endotoxin tolerance and priming in innate immune cells.

    Directory of Open Access Journals (Sweden)

    Yan Fu

    Full Text Available The innate immune system, acting as the first line of host defense, senses and adapts to foreign challenges through complex intracellular and intercellular signaling networks. Endotoxin tolerance and priming elicited by macrophages are classic examples of the complex adaptation of innate immune cells. Upon repetitive exposures to different doses of bacterial endotoxin (lipopolysaccharide or other stimulants, macrophages show either suppressed or augmented inflammatory responses compared to a single exposure to the stimulant. Endotoxin tolerance and priming are critically involved in both immune homeostasis and the pathogenesis of diverse inflammatory diseases. However, the underlying molecular mechanisms are not well understood. By means of a computational search through the parameter space of a coarse-grained three-node network with a two-stage Metropolis sampling approach, we enumerated all the network topologies that can generate priming or tolerance. We discovered three major mechanisms for priming (pathway synergy, suppressor deactivation, activator induction and one for tolerance (inhibitor persistence. These results not only explain existing experimental observations, but also reveal intriguing test scenarios for future experimental studies to clarify mechanisms of endotoxin priming and tolerance.

  3. Modified Multi Prime RSA Cryptosystem

    Science.gov (United States)

    Ghazali Kamardan, M.; Aminudin, N.; Che-Him, Norziha; Sufahani, Suliadi; Khalid, Kamil; Roslan, Rozaini

    2018-04-01

    RSA [1] is one of the mostly used cryptosystem in securing data and information. Though, it has been recently discovered that RSA has some weaknesses and in advance technology, RSA is believed to be inefficient especially when it comes to decryption. Thus, a new algorithm called Multi prime RSA, an extended version of the standard RSA is studied. Then, a modification is made to the Multi prime RSA where another keys is shared secretly between the receiver and the sender to increase the securerity. As in RSA, the methodology used for modified Multi-prime RSA also consists of three phases; 1. Key Generation in which the secret and public keys are generated and published. In this phase, the secrecy is improved by adding more prime numbers and addition of secret keys. 2. Encryption of the message using the public and secret keys given. 3. Decryption of the secret message using the secret key generated. For the decryption phase, a method called Chinese Remainder Theorem is used which helps to fasten the computation. Since Multi prime RSA use more than two prime numbers, the algorithm is more efficient and secure when compared to the standard RSA. Furthermore, in modified Multi prime RSA another secret key is introduced to increase the obstacle to the attacker. Therefore, it is strongly believed that this new algorithm is better and can be an alternative to the RSA.

  4. Cholesterol Oxidase Binds TLR2 and Modulates Functional Responses of Human Macrophages

    Directory of Open Access Journals (Sweden)

    Katarzyna Bednarska

    2014-01-01

    Full Text Available Cholesterol oxidase (ChoD is considered to be an important virulence factor for Mycobacterium tuberculosis (Mtb, but its influence on macrophage activity is unknown. Here we used Nocardia erythropolis ChoD, which is very similar to the Mtb enzyme (70% identity at the amino-acid level, to evaluate the impact of bacterial ChoD on the activity of THP-1-derived macrophages in vitro. We found that ChoD decreased the surface expression of Toll-like receptor type 2 (TLR2 and complement receptor 3 (CR3 on these macrophages. Flow cytometry and confocal microscopy showed that ChoD competed with lipoteichoic acid for ligand binding sites on TLR2 but not on CR3, suggesting that ChoD signaling is mediated via TLR2. Binding of ChoD to the membrane of macrophages had diverse effects on the activity of macrophages, activating p38 mitogen activated kinase and stimulating production of a large amount of interleukin-10. Moreover, ChoD primed macrophages to enhance the production of reactive oxygen species in response to the phorbol myristate acetate, which was reduced by “switching off” TLR-derived signaling through interleukin-1 receptor-associated kinases 1 and 4 inhibition. Our study revealed that ChoD interacts directly with macrophages via TLR2 and influences the biological activity of macrophages during the development of the initial response to infection.

  5. Optical coding theory with Prime

    CERN Document Server

    Kwong, Wing C

    2013-01-01

    Although several books cover the coding theory of wireless communications and the hardware technologies and coding techniques of optical CDMA, no book has been specifically dedicated to optical coding theory-until now. Written by renowned authorities in the field, Optical Coding Theory with Prime gathers together in one volume the fundamentals and developments of optical coding theory, with a focus on families of prime codes, supplemented with several families of non-prime codes. The book also explores potential applications to coding-based optical systems and networks. Learn How to Construct

  6. Trolling New Media: Violent Extremist Groups Recruiting Through Social Media

    Science.gov (United States)

    2015-12-01

    We must make the Internet our tool.”67 In addition to al Neda, al Qaeda maintains several other websites such as al Ansar (the Helpers ) and al...players can hone their sniper skills by executing Prime Minister Ariel Sharon.126 Just as violent extremist groups have expanded recruiting efforts

  7. Experimental Stroke Differentially Affects Discrete Subpopulations of Splenic Macrophages

    Directory of Open Access Journals (Sweden)

    Laura McCulloch

    2018-05-01

    Full Text Available Changes to the immune system after stroke are complex and can result in both pro-inflammatory and immunosuppressive consequences. Following ischemic stroke, brain resident microglia are activated and circulating monocytes are recruited to the injury site. In contrast, there is a systemic deactivation of monocytes/macrophages that may contribute to immunosuppression and the high incidence of bacterial infection experienced by stroke patients. The manipulation of macrophage subsets may be a useful therapeutic strategy to reduce infection and improve outcome in patients after stroke. Recent research has enhanced our understanding of the heterogeneity of macrophages even within the same tissue. The spleen is the largest natural reservoir of immune cells, many of which are mobilized to the site of injury after ischemic stroke and is notable for the diversity of its functionally distinct macrophage subpopulations associated with specific micro-anatomical locations. Here, we describe the effects of experimental stroke in mice on these distinct splenic macrophage subpopulations. Red pulp (RP and marginal zone macrophages (MZM specifically showed increases in density and alterations in micro-anatomical location. These changes were not due to increased recruitment from the bone marrow but may be associated with increases in local proliferation. Genes associated with phagocytosis and proteolytic processing were upregulated in the spleen after stroke with increased expression of the lysosome-associated protein lysosomal-associated membrane proteins specifically increased in RP and MZM subsets. In contrast, MHC class II expression was reduced specifically in these populations. Furthermore, genes associated with macrophage ability to communicate with other immune cells, such as co-stimulatory molecules and inflammatory cytokine production, were also downregulated in the spleen after stroke. These findings suggest that selective splenic macrophage functions

  8. Ovation Prime Real-Time

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Ovation Prime Real-Time (OPRT) product is a real-time forecast and nowcast model of auroral power and is an operational implementation of the work by Newell et...

  9. Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment

    International Nuclear Information System (INIS)

    Chanmee, Theerawut; Ontong, Pawared; Konno, Kenjiro; Itano, Naoki

    2014-01-01

    During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy

  10. Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Chanmee, Theerawut [Institute of Advanced Technology, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Ontong, Pawared [Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Konno, Kenjiro [Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Itano, Naoki, E-mail: itanon@cc.kyoto-su.ac.jp [Institute of Advanced Technology, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan)

    2014-08-13

    During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy.

  11. Psychotherapy augmentation through preconscious priming

    Directory of Open Access Journals (Sweden)

    Francois eBorgeat

    2013-03-01

    Full Text Available Objective: To test the hypothesis that repeated preconscious (masked priming of personalized positive cognitions could augment cognitive change and facilitate achievement of patients’ goals following a therapy.Methods: Twenty social phobic patients (13 women completed a 36 weeks study beginning by 12 weeks of group behavioural therapy. After the therapy, they received 6 weeks of preconscious priming and 6 weeks of a control procedure in a randomized cross-over design. The Priming condition involved listening twice daily with a passive attitude to a recording of individualized formulations of appropriate cognitions and attitudes masked by music. The Control condition involved listening to an indistinguishable recording where the formulations had been replaced by random numbers. Changes in social cognitions were measured by the Social Interaction Self Statements Test (SISST.Results: Patients improved following therapy. The Priming procedure was associated with increased positive cognitions and decreased negative cognitions on the SISST while the Control procedure was not. The Priming procedure induced more cognitive change when applied immediately after the group therapy. Conclusion: An effect of priming was observed on social phobia related cognitions in the expected direction. This self administered addition to a therapy could be seen as an augmentation strategy.

  12. Technology and Navy Recruiting

    National Research Council Canada - National Science Library

    Golfin, Peggy

    1997-01-01

    Since November 1996, CNA has participated on a Technology Task Force established by the Commander, Navy Recruiting Command, to address several issues concerning the use of technology and Navy recruiting...

  13. Identification and characterization of monoclonal antibodies specific for macrophages at intermediate stages in the tumoricidal activation pathway

    International Nuclear Information System (INIS)

    Paulnock, D.M.; Lambert, L.E.

    1990-01-01

    Macrophage activation for tumor cell killing is a multistep pathway in which responsive macrophages interact sequentially with priming and triggering stimuli in the acquisition of full tumoricidal activity. A number of mediators have been identified which have activating capability, including in particular IFN-gamma and bacterial LPS. Although the synergistic functional response of normal macrophages to sequential incubation with these activation signals has been well-established, characterization of the intermediate stages in the activation pathway has been difficult. We have developed a model system for examination of various aspects of macrophage activation, through the use of the murine macrophage tumor cell line, RAW 264.7. These cells, like normal macrophages, exhibit a strict requirement for interaction with both IFN-gamma and LPS in the development of tumor cytolytic activity. In addition, these cells can be stably primed by the administration of gamma-radiation. In the studies reported here, we have used RAW 264.7 cells treated with IFN-gamma alone or with IFN-gamma plus LPS to stimulate the production of rat mAb probes recognizing cell surface changes occurring during the activation process. In this way we have identified three Ag associated with intermediate stages of the activation process. One Ag, TM-1, is expressed on RAW 264.7 cells primed by IFN-gamma or gamma-radiation. This surface Ag thus identifies cells at the primed cell intermediate stage of the tumoricidal activation pathway regardless of the mechanism of activation. A second Ag, TM-2, is expressed on IFN-treated RAW 264.7 cells but not on RAW 264.7 cells primed with gamma-radiation alone. Expression of this Ag can be induced by treatment of irradiated cells with IFN-gamma, but is not induced by IFN-gamma treatment of a noncytolytic cell line, WEHI-3

  14. Sequential Stereotype Priming: A Meta-Analysis.

    Science.gov (United States)

    Kidder, Ciara K; White, Katherine R; Hinojos, Michelle R; Sandoval, Mayra; Crites, Stephen L

    2017-08-01

    Psychological interest in stereotype measurement has spanned nearly a century, with researchers adopting implicit measures in the 1980s to complement explicit measures. One of the most frequently used implicit measures of stereotypes is the sequential priming paradigm. The current meta-analysis examines stereotype priming, focusing specifically on this paradigm. To contribute to ongoing discussions regarding methodological rigor in social psychology, one primary goal was to identify methodological moderators of the stereotype priming effect-whether priming is due to a relation between the prime and target stimuli, the prime and target response, participant task, stereotype dimension, stimulus onset asynchrony (SOA), and stimuli type. Data from 39 studies yielded 87 individual effect sizes from 5,497 participants. Analyses revealed that stereotype priming is significantly moderated by the presence of prime-response relations, participant task, stereotype dimension, target stimulus type, SOA, and prime repetition. These results carry both practical and theoretical implications for future research on stereotype priming.

  15. On the Control of Single-Prime Negative Priming: The Effects of Practice and Time Course

    Science.gov (United States)

    Chao, Hsuan-Fu

    2009-01-01

    Single-prime negative priming refers to the phenomenon wherein repetition of a prime as the probe target results in delayed response. Sometimes this effect has been found to be contingent on participants' unawareness of the primes, and sometimes it has not. Further, sometimes this effect has been found to be eliminated when the prime could predict…

  16. TNF Counterbalances the Emergence of M2 Tumor Macrophages

    Directory of Open Access Journals (Sweden)

    Franz Kratochvill

    2015-09-01

    Full Text Available Cancer can involve non-resolving, persistent inflammation where varying numbers of tumor-associated macrophages (TAMs infiltrate and adopt different activation states between anti-tumor M1 and pro-tumor M2 phenotypes. Here, we resolve a cascade causing differential macrophage phenotypes in the tumor microenvironment. Reduction in TNF mRNA production or loss of type I TNF receptor signaling resulted in a striking pattern of enhanced M2 mRNA expression. M2 gene expression was driven in part by IL-13 from eosinophils co-recruited with inflammatory monocytes, a pathway that was suppressed by TNF. Our data define regulatory nodes within the tumor microenvironment that balance M1 and M2 populations. Our results show macrophage polarization in cancer is dynamic and dependent on the balance between TNF and IL-13, thus providing a strategy for manipulating TAMs.

  17. The Recruitment Process:

    DEFF Research Database (Denmark)

    Holm, Anna

    , which were carried out in Denmark in 2008-2009 using qualitative research methods, revealed changes in the sequence, divisibility and repetitiveness of a number of recruitment tasks and subtasks. The new recruitment process design was identified and presented in the paper. The study concluded......The aim of this research was to determine whether the introduction of e-recruitment has an impact on the process and underlying tasks, subtasks and activities of recruitment. Three large organizations with well-established e-recruitment practices were included in the study. The three case studies...

  18. Macrophage immunoregulatory pathways in tuberculosis.

    Science.gov (United States)

    Rajaram, Murugesan V S; Ni, Bin; Dodd, Claire E; Schlesinger, Larry S

    2014-12-01

    Macrophages, the major host cells harboring Mycobacterium tuberculosis (M.tb), are a heterogeneous cell type depending on their tissue of origin and host they are derived from. Significant discord in macrophage responses to M.tb exists due to differences in M.tb strains and the various types of macrophages used to study tuberculosis (TB). This review will summarize current concepts regarding macrophage responses to M.tb infection, while pointing out relevant differences in experimental outcomes due to the use of divergent model systems. A brief description of the lung environment is included since there is increasing evidence that the alveolar macrophage (AM) has immunoregulatory properties that can delay optimal protective host immune responses. In this context, this review focuses on selected macrophage immunoregulatory pattern recognition receptors (PRRs), cytokines, negative regulators of inflammation, lipid mediators and microRNAs (miRNAs). Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Cardiac macrophage biology in the steady-state heart, the aging heart, and following myocardial infarction

    Science.gov (United States)

    Ma, Yonggang; Mouton, Alan J.; Lindsey, Merry L.

    2018-01-01

    Macrophages play critical roles in homeostatic maintenance of the myocardium under normal conditions and in tissue repair after injury. In the steady-state heart, resident cardiac macrophages remove senescent and dying cells and facilitate electrical conduction. In the aging heart, the shift in macrophage phenotype to a proinflammatory subtype leads to inflammaging. Following myocardial infarction (MI), macrophages recruited to the infarct produce both proinflammatory and anti-inflammatory mediators (cytokines, chemokines, matrix metalloproteinases, and growth factors), phagocytize dead cells, and promote angiogenesis and scar formation. These diverse properties are attributed to distinct macrophage subtypes and polarization status. Infarct macrophages exhibit a proinflammatory M1 phenotype early and become polarized toward an anti-inflammatory M2 phenotype later post- MI. Although this classification system is oversimplified and needs to be refined to accommodate the multiple different macrophage subtypes that have been recently identified, general concepts on macrophage roles are independent of subtype classification. This review summarizes current knowledge about cardiac macrophage origins, roles, and phenotypes in the steady state, with aging, and after MI, as well as highlights outstanding areas of investigation. PMID:29106912

  20. Tie2 signaling cooperates with TNF to promote the pro-inflammatory activation of human macrophages independently of macrophage functional phenotype.

    Science.gov (United States)

    García, Samuel; Krausz, Sarah; Ambarus, Carmen A; Fernández, Beatriz Malvar; Hartkamp, Linda M; van Es, Inge E; Hamann, Jörg; Baeten, Dominique L; Tak, Paul P; Reedquist, Kris A

    2014-01-01

    Angiopoietin (Ang) -1 and -2 and their receptor Tie2 play critical roles in regulating angiogenic processes during development, homeostasis, tumorigenesis, inflammation and tissue repair. Tie2 signaling is best characterized in endothelial cells, but a subset of human and murine circulating monocytes/macrophages essential to solid tumor formation express Tie2 and display immunosuppressive properties consistent with M2 macrophage polarization. However, we have recently shown that Tie2 is strongly activated in pro-inflammatory macrophages present in rheumatoid arthritis patient synovial tissue. Here we examined the relationship between Tie2 expression and function during human macrophage polarization. Tie2 expression was observed under all polarization conditions, but was highest in IFN-γ and IL-10 -differentiated macrophages. While TNF enhanced expression of a common restricted set of genes involved in angiogenesis and inflammation in GM-CSF, IFN-γ and IL-10 -differentiated macrophages, expression of multiple chemokines and cytokines, including CXCL3, CXCL5, CXCL8, IL6, and IL12B was further augmented in the presence of Ang-1 and Ang-2, via Tie2 activation of JAK/STAT signaling. Conditioned medium from macrophages stimulated with Ang-1 or Ang-2 in combination with TNF, sustained monocyte recruitment. Our findings suggest a general role for Tie2 in cooperatively promoting the inflammatory activation of macrophages, independently of polarization conditions.

  1. Biology of Bony Fish Macrophages

    OpenAIRE

    Hodgkinson, Jordan W.; Grayfer, Leon; Belosevic, Miodrag

    2015-01-01

    Macrophages are found across all vertebrate species, reside in virtually all animal tissues, and play critical roles in host protection and homeostasis. Various mechanisms determine and regulate the highly plastic functional phenotypes of macrophages, including antimicrobial host defenses (pro-inflammatory, M1-type), and resolution and repair functions (anti-inflammatory/regulatory, M2-type). The study of inflammatory macrophages in immune defense of teleosts has garnered much attention, and ...

  2. Structurally well-defined macrophage activating factor derived from vitamin D3-binding protein has a potent adjuvant activity for immunization.

    Science.gov (United States)

    Yamamoto, N; Naraparaju, V R

    1998-06-01

    Freund's adjuvant produced severe inflammation that augments development of antibodies. Thus, mixed administration of antigens with adjuvant was not required as long as inflammation was induced in the hosts. Since macrophage activation for phagocytosis and antigen processing is the first step of antibody development, inflammation-primed macrophage activation plays a major role in immune development. Therefore, macrophage activating factor should act as an adjuvant for immunization. The inflammation-primed macrophage activation process is the major macrophage activating cascade that requires participation of serum vitamin D3-binding protein (DBP; human DBP is known as Gc protein) and glycosidases of B and T lymphocytes. Stepwise incubation of Gc protein with immobilized beta-galactosidase and sialidase efficiently generated the most potent macrophage activating factor (designated GcMAF) we have ever encountered. Administration of GcMAF (20 or 100 pg/mouse) resulted in stimulation of the progenitor cells for extensive mitogenesis and activation of macrophages. Administration of GcMAF (100 pg/mouse) along with immunization of mice with sheep red blood cells (SRBC) produced a large number of anti-SRBC antibody secreting splenic cells in 2-4 days. Thus, GcMAF has a potent adjuvant activity for immunization. Although malignant tumours are poorly immunogenic, 4 days after GcMAF-primed immunization of mice with heat-killed Ehrlich ascites tumour cells, the ascites tumour was no longer transplantable in these mice.

  3. Bioelectric modulation of macrophage polarization

    Science.gov (United States)

    Li, Chunmei; Levin, Michael; Kaplan, David L.

    2016-02-01

    Macrophages play a critical role in regulating wound healing and tissue regeneration by changing their polarization state in response to local microenvironmental stimuli. The native roles of polarized macrophages encompass biomaterials and tissue remodeling needs, yet harnessing or directing the polarization response has been largely absent as a potential strategy to exploit in regenerative medicine to date. Recent data have revealed that specific alteration of cells’ resting potential (Vmem) is a powerful tool to direct proliferation and differentiation in a number of complex tissues, such as limb regeneration, craniofacial patterning and tumorigenesis. In this study, we explored the bioelectric modulation of macrophage polarization by targeting ATP sensitive potassium channels (KATP). Glibenclamide (KATP blocker) and pinacidil (KATP opener) treatment not only affect macrophage polarization, but also influence the phenotype of prepolarized macrophages. Furthermore, modulation of cell membrane electrical properties can fine-tune macrophage plasticity. Glibenclamide decreased the secretion and gene expression of selected M1 markers, while pinacidil augmented M1 markers. More interestingly, glibencalmide promoted macrophage alternative activation by enhancing certain M2 markers during M2 polarization. These findings suggest that control of bioelectric properties of macrophages could offer a promising approach to regulate macrophage phenotype as a useful tool in regenerative medicine.

  4. The structure factor of primes

    Science.gov (United States)

    Zhang, G.; Martelli, F.; Torquato, S.

    2018-03-01

    Although the prime numbers are deterministic, they can be viewed, by some measures, as pseudo-random numbers. In this article, we numerically study the pair statistics of the primes using statistical-mechanical methods, particularly the structure factor S(k) in an interval M ≤slant p ≤slant M + L with M large, and L/M smaller than unity. We show that the structure factor of the prime-number configurations in such intervals exhibits well-defined Bragg-like peaks along with a small ‘diffuse’ contribution. This indicates that primes are appreciably more correlated and ordered than previously thought. Our numerical results definitively suggest an explicit formula for the locations and heights of the peaks. This formula predicts infinitely many peaks in any non-zero interval, similar to the behavior of quasicrystals. However, primes differ from quasicrystals in that the ratio between the location of any two predicted peaks is rational. We also show numerically that the diffuse part decays slowly as M and L increases. This suggests that the diffuse part vanishes in an appropriate infinite-system-size limit.

  5. Antigen Requirements for Efficient Priming of CD8+ T Cells by Leishmania major-Infected Dendritic Cells

    Science.gov (United States)

    Bertholet, Sylvie; Debrabant, Alain; Afrin, Farhat; Caler, Elisabeth; Mendez, Susana; Tabbara, Khaled S.; Belkaid, Yasmine; Sacks, David L.

    2005-01-01

    CD4+ and CD8+ T-cell responses have been shown to be critical for the development and maintenance of acquired resistance to infections with the protozoan parasite Leishmania major. Monitoring the development of immunodominant or clonally restricted T-cell subsets in response to infection has been difficult, however, due to the paucity of known epitopes. We have analyzed the potential of L. major transgenic parasites, expressing the model antigen ovalbumin (OVA), to be presented by antigen-presenting cells to OVA-specific OT-II CD4+ or OT-I CD8+ T cells. Truncated OVA was expressed in L. major as part of a secreted or nonsecreted chimeric protein with L. donovani 3′ nucleotidase (NT-OVA). Dendritic cells (DC) but not macrophages infected with L. major that secreted NT-OVA could prime OT-I T cells to proliferate and release gamma interferon. A diminished T-cell response was observed when DC were infected with parasites expressing nonsecreted NT-OVA or with heat-killed parasites. Inoculation of mice with transgenic parasites elicited the proliferation of adoptively transferred OT-I T cells and their recruitment to the site of infection in the skin. Together, these results demonstrate the possibility of targeting heterologous antigens to specific cellular compartments in L. major and suggest that proteins secreted or released by L. major in infected DC are a major source of peptides for the generation of parasite-specific CD8+ T cells. The ability of L. major transgenic parasites to activate OT-I CD8+ T cells in vivo will permit the analysis of parasite-driven T-cell expansion, differentiation, and recruitment at the clonal level. PMID:16177338

  6. MicroRNAs Control Macrophage Formation and Activation: The Inflammatory Link between Obesity and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Richard Cheng-An Chang

    2014-07-01

    Full Text Available Activation and recruitment of resident macrophages in tissues in response to physiological stress are crucial regulatory processes in promoting the development of obesity-associated metabolic disorders and cardiovascular diseases. Recent studies have provided compelling evidence that microRNAs play important roles in modulating monocyte formation, macrophage maturation, infiltration into tissues and activation. Macrophage-dependent systemic physiological and tissue-specific responses also involve cell-cell interactions between macrophages and host tissue niche cell components, including other tissue-resident immune cell lineages, adipocytes, vascular smooth muscle and others. In this review, we highlight the roles of microRNAs in regulating the development and function of macrophages in the context of obesity, which could provide insights into the pathogenesis of obesity-related metabolic syndrome and cardiovascular diseases.

  7. Interaction of differentiated human adipocytes with macrophages leads to trogocytosis and selective IL-6 secretion

    OpenAIRE

    Sárvári, Anitta Kinga; Doan-Xuan, Quang-Minh; Bacsó, Zsolt; Csomós, István; Balajthy, Zoltán; Fésüs, László

    2015-01-01

    Obesity leads to adipose tissue inflammation that is characterized by increased release of proinflammatory molecules and the recruitment of activated immune cells. Although macrophages are present in the highest number among the immune cells in obese adipose tissue, not much is known about their direct interaction with adipocytes. We have introduced an ex vivo experimental system to characterize the cellular interactions and the profile of secreted cytokines in cocultures of macrophages and h...

  8. Italy's Prime Minister visits CERN

    CERN Multimedia

    Stefania Pandolfi

    2015-01-01

    On Tuesday, 7 July 2015, the Prime Minister of the Italian Republic, Matteo Renzi, visited CERN. He was accompanied by a delegation that included Italy's Minister for Education, University and Research, Stefania Giannini.   From left to right: Fernando Ferroni, President of the Istituto Nazionale di Fisica Nucleare (INFN); Sergio Bertolucci, CERN Director for Research and Scientific Computing; Stefania Giannini, Italy's Minister of Education, University and Research; Matteo Renzi, Prime Minister of the Italian Republic; Fabiola Gianotti, CERN Director-General Designate; Rolf Heuer, CERN Director-General.   The Prime Minister was welcomed by members of the CERN Management together with former CERN Director-General and Senator for Life of the Italian Republic, Carlo Rubbia. After a brief general introduction to CERN’s activities by Rolf Heuer, the Italian delegation visited LHC Point 1. After a tour of the ATLAS control room, they donned helmets to visit th...

  9. Differentiation of the endometrial macrophage during pregnancy in the cow.

    Directory of Open Access Journals (Sweden)

    Lilian J Oliveira

    Full Text Available BACKGROUND: The presence of conceptus alloantigens necessitates changes in maternal immune function. One player in this process may be the macrophage. In the cow, there is large-scale recruitment of macrophages expressing CD68 and CD14 to the uterine endometrium during pregnancy. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, the function of endometrial macrophages during pregnancy was inferred by comparison of the transcriptome of endometrial CD14(+ cells isolated from pregnant cows as compared to that of blood CD14(+ cells. The pattern of gene expression was largely similar for CD14(+ cells from both sources, suggesting that cells from both tissues are from the monocyte/macrophage lineage. A total of 1,364 unique genes were differentially expressed, with 680 genes upregulated in endometrial CD14(+ cells as compared to blood CD14(+ cells and with 674 genes downregulated in endometrial CD14(+ cells as compared to blood CD14(+ cells. Twelve genes characteristic of M2 activated macrophages (SLCO2B1, GATM, MRC1, ALDH1A1, PTGS1, RNASE6, CLEC7A, DPEP2, CD163, CCL22, CCL24, and CDH1 were upregulated in endometrial CD14(+ cells. M2 macrophages play roles in immune regulation, tissue remodeling, angiogenesis and apoptosis. Consistent with a role in tissue remodeling, there was over-representation of differentially expressed genes in endometrium for three ontologies related to proteolysis. A role in apoptosis is suggested by the observation that the most overrepresented gene in endometrial CD14(+ cells was GZMA. CONCLUSIONS: Results indicate that at least a subpopulation of endometrial macrophages cells differentiates along an M2 activation pathway during pregnancy and that the cells are likely to play roles in immune regulation, tissue remodeling, angiogenesis, and apoptosis.

  10. Pharmacological Regulation of Neuropathic Pain Driven by Inflammatory Macrophages

    Directory of Open Access Journals (Sweden)

    Norikazu Kiguchi

    2017-11-01

    Full Text Available Neuropathic pain can have a major effect on quality of life but current therapies are often inadequate. Growing evidence suggests that neuropathic pain induced by nerve damage is caused by chronic inflammation. Upon nerve injury, damaged cells secrete pro-inflammatory molecules that activate cells in the surrounding tissue and recruit circulating leukocytes to the site of injury. Among these, the most abundant cell type is macrophages, which produce several key molecules involved in pain enhancement, including cytokines and chemokines. Given their central role in the regulation of peripheral sensitization, macrophage-derived cytokines and chemokines could be useful targets for the development of novel therapeutics. Inhibition of key pro-inflammatory cytokines and chemokines prevents neuroinflammation and neuropathic pain; moreover, recent studies have demonstrated the effectiveness of pharmacological inhibition of inflammatory (M1 macrophages. Nicotinic acetylcholine receptor ligands and T helper type 2 cytokines that reduce M1 macrophages are able to relieve neuropathic pain. Future translational studies in non-human primates will be crucial for determining the regulatory mechanisms underlying neuroinflammation-associated neuropathic pain. In turn, this knowledge will assist in the development of novel pharmacotherapies targeting macrophage-driven neuroinflammation for the treatment of intractable neuropathic pain.

  11. E-recruitment

    DEFF Research Database (Denmark)

    Holm, Anna

    2012-01-01

    E-recruitment, also known as online or web-based recruitment, is little discussed in research from an organizational perspective. The purpose of this chapter is therefore to analyze and discuss the process of e-recruitment, its key constituents and organizing principles. In doing so I draw...... on the results of a qualitative study conducted in 2008-2009, and on data stemming from industrial reports, articles from practitioner magazines, and in-depth interviews. The chapter provides a summary of e-recruitment properties and a composite matrix of the overall elements of e-recruitment organizing. E-recruitment...... is viewed as a case of virtual organizing- the organization of processes and activities which, via technology and human agents, facilitate time- and space-independent interaction and collaboration. In closure I offer a brief discussion of implications of the findings for HR managers and professionals...

  12. Macrophage elastase (MMP-12: a pro-inflammatory mediator?

    Directory of Open Access Journals (Sweden)

    Soazig Nénan

    2005-03-01

    Full Text Available As many metalloproteinases (MMPs, macrophage elastase (MMP-12 is able to degrade extracellular matrix components such as elastin and is involved in tissue remodeling processes. Studies using animal models of acute and chronic pulmonary inflammatory diseases, such as pulmonary fibrosis and chronic obstrutive pulmonary disease (COPD, have given evidences that MMP-12 is an important mediator of the pathogenesis of these diseases. However, as very few data regarding the direct involvement of MMP-12 in inflammatory process in the airways were available, we have instilled a recombinant form of human MMP-12 (rhMMP-12 in mouse airways. Hence, we have demonstrated that this instillation induced a severe inflammatory cell recruitment characterized by an early accumulation of neutrophils correlated with an increase in proinflammatory cytokines and in gelatinases and then by a relatively stable recruitment of macrophages in the lungs over a period of ten days. Another recent study suggests that resident alveolar macrophages and recruited neutrophils are not involved in the delayed macrophage recruitment. However, epithelial cells could be one of the main targets of rhMMP-12 in our model. We have also reported that a corticoid, dexamethasone, phosphodiesterase 4 inhibitor, rolipram and a non-selective MMP inhibitor, marimastat could reverse some of these inflammatory events. These data indicate that our rhMMP-12 model could mimic some of the inflammatory features observed in COPD patients and could be used for the pharmacological evaluation of new anti-inflammatory treatment. In this review, data demonstrating the involvement of MMP-12 in the pathogenesis of pulmonary fibrosis and COPD as well as our data showing a pro-inflammatory role for MMP-12 in mouse airways will be summarized.

  13. Instant PrimeFaces starter

    CERN Document Server

    Hlavats, Ian

    2013-01-01

    Get to grips with a new technology, understand what it is and what it can do for you, and then get to work with the most important features and tasks. Instant Primefaces Starter is a fast-paced, introductory guide designed to give you all the information you need to start using Primfaces, instantly.Instant PrimeFaces Starter is great for developers looking to get started quickly with PrimeFaces. It's assumed that you have some JSF experience already, as well as familiarity with other Java technologies such as CDI and JPA and an understanding of MVC principles, object-relational mapping (ORM),

  14. Enhanced M1 macrophage polarization in human helicobacter pylori-associated atrophic gastritis and in vaccinated mice.

    Directory of Open Access Journals (Sweden)

    Marianne Quiding-Järbrink

    Full Text Available BACKGROUND: Infection with Helicobacter pylori triggers a chronic gastric inflammation that can progress to atrophy and gastric adenocarcinoma. Polarization of macrophages is a characteristic of both cancer and infection, and may promote progression or resolution of disease. However, the role of macrophages and their polarization during H. pylori infection has not been well defined. METHODOLOGY/PRINCIPAL FINDINGS: By using a mouse model of infection and gastric biopsies from 29 individuals, we have analyzed macrophage recruitment and polarization during H. pylori infection by flow cytometry and real-time PCR. We found a sequential recruitment of neutrophils, eosinophils and macrophages to the gastric mucosa of infected mice. Gene expression analysis of stomach tissue and sorted macrophages revealed that gastric macrophages were polarized to M1 after H. pylori infection, and this process was substantially accelerated by prior vaccination. Human H. pylori infection was characterized by a mixed M1/M2 polarization of macrophages. However, in H. pylori-associated atrophic gastritis, the expression of inducible nitric oxide synthase was markedly increased compared to uncomplicated gastritis, indicative of an enhanced M1 macrophage polarization in this pre-malignant lesion. CONCLUSIONS/SIGNIFICANCE: These results show that vaccination of mice against H. pylori amplifies M1 polarization of gastric macrophages, and that a similar enhanced M1 polarization is present in human H. pylori-induced atrophic gastritis.

  15. The pros and cons of masked priming.

    Science.gov (United States)

    Forster, K I

    1998-03-01

    Masked priming paradigms offer the promise of tapping automatic, strategy-free lexical processing, as evidenced by the lack of expectancy disconfirmation effects, and proportionality effects in semantic priming experiments. But several recent findings suggest the effects may be prelexical. These findings concern nonword priming effects in lexical decision and naming, the effects of mixed-case presentation on nonword priming, and the dependence of priming on the nature of the distractors in lexical decision, suggesting possible strategy effects. The theory underlying each of these effects is discussed, and alternative explanations are developed that do not preclude a lexical basis for masked priming effects.

  16. Epigenetic regulation of macrophage function

    NARCIS (Netherlands)

    Hoeksema, M.A.

    2016-01-01

    Atherosclerosis is a lipid-driven chronic inflammatory disorder with a key role for macrophages in all disease stages. Macrophages are involved as scavengers of lipids, regulate inflammation, attract other immune cells and contribute to the resolution of inflammation, fibrosis and plaque stability.

  17. Biology of Bony Fish Macrophages

    Directory of Open Access Journals (Sweden)

    Jordan W. Hodgkinson

    2015-11-01

    Full Text Available Macrophages are found across all vertebrate species, reside in virtually all animal tissues, and play critical roles in host protection and homeostasis. Various mechanisms determine and regulate the highly plastic functional phenotypes of macrophages, including antimicrobial host defenses (pro-inflammatory, M1-type, and resolution and repair functions (anti-inflammatory/regulatory, M2-type. The study of inflammatory macrophages in immune defense of teleosts has garnered much attention, and antimicrobial mechanisms of these cells have been extensively studied in various fish models. Intriguingly, both similarities and differences have been documented for the regulation of lower vertebrate macrophage antimicrobial defenses, as compared to what has been described in mammals. Advances in our understanding of the teleost macrophage M2 phenotypes likewise suggest functional conservation through similar and distinct regulatory strategies, compared to their mammalian counterparts. In this review, we discuss the current understanding of the molecular mechanisms governing teleost macrophage functional heterogeneity, including monopoetic development, classical macrophage inflammatory and antimicrobial responses as well as alternative macrophage polarization towards tissues repair and resolution of inflammation.

  18. Biology of Bony Fish Macrophages.

    Science.gov (United States)

    Hodgkinson, Jordan W; Grayfer, Leon; Belosevic, Miodrag

    2015-11-30

    Macrophages are found across all vertebrate species, reside in virtually all animal tissues, and play critical roles in host protection and homeostasis. Various mechanisms determine and regulate the highly plastic functional phenotypes of macrophages, including antimicrobial host defenses (pro-inflammatory, M1-type), and resolution and repair functions (anti-inflammatory/regulatory, M2-type). The study of inflammatory macrophages in immune defense of teleosts has garnered much attention, and antimicrobial mechanisms of these cells have been extensively studied in various fish models. Intriguingly, both similarities and differences have been documented for the regulation of lower vertebrate macrophage antimicrobial defenses, as compared to what has been described in mammals. Advances in our understanding of the teleost macrophage M2 phenotypes likewise suggest functional conservation through similar and distinct regulatory strategies, compared to their mammalian counterparts. In this review, we discuss the current understanding of the molecular mechanisms governing teleost macrophage functional heterogeneity, including monopoetic development, classical macrophage inflammatory and antimicrobial responses as well as alternative macrophage polarization towards tissues repair and resolution of inflammation.

  19. The neural basis of love as a subliminal prime: an event-related functional magnetic resonance imaging study.

    Science.gov (United States)

    Ortigue, S; Bianchi-Demicheli, F; Hamilton, A F de C; Grafton, S T

    2007-07-01

    Throughout the ages, love has been defined as a motivated and goal-directed mechanism with explicit and implicit mechanisms. Recent evidence demonstrated that the explicit representation of love recruits subcorticocortical pathways mediating reward, emotion, and motivation systems. However, the neural basis of the implicit (unconscious) representation of love remains unknown. To assess this question, we combined event-related functional magnetic resonance imaging (fMRI) with a behavioral subliminal priming paradigm embedded in a lexical decision task. In this task, the name of either a beloved partner, a neutral friend, or a passionate hobby was subliminally presented before a target stimulus (word, nonword, or blank), and participants were required to decide if the target was a word or not. Behavioral results showed that subliminal presentation of either a beloved's name (love prime) or a passion descriptor (passion prime) enhanced reaction times in a similar fashion. Subliminal presentation of a friend's name (friend prime) did not show any beneficial effects. Functional results showed that subliminal priming with a beloved's name (as opposed to either a friend's name or a passion descriptor) specifically recruited brain areas involved in abstract representations of others and the self, in addition to motivation circuits shared with other sources of passion. More precisely, love primes recruited the fusiform and angular gyri. Our findings suggest that love, as a subliminal prime, involves a specific neural network that surpasses a dopaminergic-motivation system.

  20. Yersinia pestis Requires Host Rab1b for Survival in Macrophages.

    Directory of Open Access Journals (Sweden)

    Michael G Connor

    2015-10-01

    Full Text Available Yersinia pestis is a facultative intracellular pathogen that causes the disease known as plague. During infection of macrophages Y. pestis actively evades the normal phagosomal maturation pathway to establish a replicative niche within the cell. However, the mechanisms used by Y. pestis to subvert killing by the macrophage are unknown. Host Rab GTPases are central mediators of vesicular trafficking and are commonly targeted by bacterial pathogens to alter phagosome maturation and killing by macrophages. Here we demonstrate for the first time that host Rab1b is required for Y. pestis to effectively evade killing by macrophages. We also show that Rab1b is specifically recruited to the Yersinia containing vacuole (YCV and that Y. pestis is unable to subvert YCV acidification when Rab1b expression is knocked down in macrophages. Furthermore, Rab1b knockdown also altered the frequency of association between the YCV with the lysosomal marker Lamp1, suggesting that Rab1b recruitment to the YCV directly inhibits phagosome maturation. Finally, we show that Rab1b knockdown also impacts the pH of the Legionella pneumophila containing vacuole, another pathogen that recruits Rab1b to its vacuole. Together these data identify a novel role for Rab1b in the subversion of phagosome maturation by intracellular pathogens and suggest that recruitment of Rab1b to the pathogen containing vacuole may be a conserved mechanism to control vacuole pH.

  1. Characteristic of Rings. Prime Fields

    Directory of Open Access Journals (Sweden)

    Schwarzweller Christoph

    2015-12-01

    Full Text Available The notion of the characteristic of rings and its basic properties are formalized [14], [39], [20]. Classification of prime fields in terms of isomorphisms with appropriate fields (ℚ or ℤ/p are presented. To facilitate reasonings within the field of rational numbers, values of numerators and denominators of basic operations over rationals are computed.

  2. Prime Suspect, Second Row Center

    Science.gov (United States)

    Laird, Ellen A.

    2011-01-01

    His father had been hacked to death in his own bed with an ax the previous November. His mother was similarly brutalized and left for dead with her husband but survived. On the last Monday of that August, after several months and many investigative twists, turns, and fumbles, there sat the son--the prime suspect--in Ellen Laird's literature class,…

  3. On primes in Lucas sequences

    Czech Academy of Sciences Publication Activity Database

    Křížek, Michal; Somer, L.

    2015-01-01

    Roč. 53, č. 1 (2015), s. 2-23 ISSN 0015-0517 R&D Projects: GA ČR GA14-02067S Institutional support: RVO:67985840 Keywords : Lucas sequence * primes Subject RIV: BA - General Mathematics http://www.fq.math.ca/Abstracts/53-1/somer.pdf

  4. Macrophages under pressure: the role of macrophage polarization in hypertension.

    Science.gov (United States)

    Harwani, Sailesh C

    2018-01-01

    Hypertension is a multifactorial disease involving the nervous, renal, and cardiovascular systems. Macrophages are the most abundant and ubiquitous immune cells, placing them in a unique position to serve as key mediators between these components. The polarization of macrophages confers vast phenotypic and functional plasticity, allowing them to act as proinflammatory, homeostatic, and anti-inflammatory agents. Key differences between the M1 and M2 phenotypes, the 2 subsets at the extremes of this polarization spectrum, place macrophages at a juncture to mediate many mechanisms involved in the pathogenesis of hypertension. Neuronal and non-neuronal regulation of the immune system, that is, the "neuroimmuno" axis, plays an integral role in the polarization of macrophages. In hypertension, the neuroimmuno axis results in synchronization of macrophage mobilization from immune cell reservoirs and their chemotaxis, via increased expression of chemoattractants, to end organs critical in the development of hypertension. This complicated system is largely coordinated by the dichotomous actions of the autonomic neuronal and non-neuronal activation of cholinergic, adrenergic, and neurohormonal receptors on macrophages, leading to their ability to "switch" between phenotypes at sites of active inflammation. Data from experimental models and human studies are in concordance with each other and support a central role for macrophage polarization in the pathogenesis of hypertension. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Recruitment of general practices

    DEFF Research Database (Denmark)

    Riis, Allan; Jensen, Cathrine Elgaard; Maindal, Helle Terkildsen

    2016-01-01

    -factors as determinants for successfully recruiting healthcare professionals: relationships, reputation, requirements, rewards, reciprocity, resolution, and respect. Method: This is a process evaluation of the seven R-factors. We applied these factors to guide the design of our recruitment strategy as well as to make......Introduction: Health service research often involves the active participation of healthcare professionals. However, their ability and commitment to research varies. This can cause recruitment difficulties and thereby prolong the study period and inflate budgets. Solberg has identified seven R...... adjustments when recruiting general practices in a guideline implementation study. In the guideline implementation study, we studied the effect of outreach visits, quality reports, and new patient stratification tools for low back pain patients. Results: During a period of 15 months, we recruited 60 practices...

  6. A Time- and Compartment-Specific Activation of Lung Macrophages in Hypoxic Pulmonary Hypertension.

    Science.gov (United States)

    Pugliese, Steven C; Kumar, Sushil; Janssen, William J; Graham, Brian B; Frid, Maria G; Riddle, Suzette R; El Kasmi, Karim C; Stenmark, Kurt R

    2017-06-15

    Studies in various animal models suggest an important role for pulmonary macrophages in the pathogenesis of pulmonary hypertension (PH). Yet, the molecular mechanisms characterizing the functional macrophage phenotype relative to time and pulmonary localization and compartmentalization remain largely unknown. In this study, we used a hypoxic murine model of PH in combination with FACS to quantify and isolate lung macrophages from two compartments over time and characterize their programing via RNA sequencing approaches. In response to hypoxia, we found an early increase in macrophage number that was restricted to the interstitial/perivascular compartment, without recruitment of macrophages to the alveolar compartment or changes in the number of resident alveolar macrophages. Principal component analysis demonstrated significant differences in overall gene expression between alveolar and interstitial macrophages (IMs) at baseline and after 4 and 14 d hypoxic exposure. Alveolar macrophages at both day 4 and 14 and IMs at day 4 shared a conserved hypoxia program characterized by mitochondrial dysfunction, proinflammatory gene activation, and mTORC1 signaling, whereas IMs at day 14 demonstrated a unique anti-inflammatory/proreparative programming state. We conclude that the pathogenesis of vascular remodeling in hypoxic PH involves an early compartment-independent activation of lung macrophages toward a conserved hypoxia program, with the development of compartment-specific programs later in the course of the disease. Thus, harnessing time- and compartment-specific differences in lung macrophage polarization needs to be considered in the therapeutic targeting of macrophages in hypoxic PH and potentially other inflammatory lung diseases. Copyright © 2017 by The American Association of Immunologists, Inc.

  7. DMPD: Macrophage-stimulating protein and RON receptor tyrosine kinase: potentialregulators of macrophage inflammatory activities. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12472665 Macrophage-stimulating protein and RON receptor tyrosine kinase: potential...:545-53. (.png) (.svg) (.html) (.csml) Show Macrophage-stimulating protein and RON receptor tyrosine kinase:...le Macrophage-stimulating protein and RON receptor tyrosine kinase: potentialregulators of macrophage inflam

  8. Structural priming, action planning, and grammar.

    Science.gov (United States)

    MacDonald, Maryellen C; Weiss, Daniel J

    2017-01-01

    Structural priming is poorly understood and cannot inform accounts of grammar for two reasons. First, those who view performance as grammar + processing will always be able to attribute psycholinguistic data to processing rather than grammar. Second, structural priming may be simply an example of hysteresis effects in general action planning. If so, then priming offers no special insight into grammar.

  9. Priming methods in semantics and pragmatics.

    Science.gov (United States)

    Maldonado, Mora; Spector, Benjamin; Chemla, Emmanuel

    2017-01-01

    Structural priming is a powerful method to inform linguistic theories. We argue that this method extends nicely beyond syntax to theories of meaning. Priming, however, should still be seen as only one of the tools available for linguistic data collection. Specifically, because priming can occur at different, potentially conflicting levels, it cannot detect every aspect of linguistic representations.

  10. We Can Still Be Friends: IFN-γ Breaks Up Macrophage Enhancers.

    Science.gov (United States)

    Novakovic, Boris; Wang, Cheng; Logie, Colin

    2017-08-15

    Interferon (IFN)-γ can prime macrophages for inflammatory responses by several mechanisms, including enhancer establishment and gene activation. In this issue of Immunity, Kang et al. (2017) provide insight into the mechanisms of IFN-γ-mediated gene repression as they show that IFN-γ promotes the disassembly of select active enhancers by interfering with enhancer-binding transcription factor MAF. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Aggressive priming online: Facebook adverts can prime aggressive cognitions

    OpenAIRE

    Buchanan, Tom

    2015-01-01

    Through the process of priming, incidental stimuli in our environments can influence our thoughts, feelings and behavior. This may be true of incidental stimuli in online environments, such as adverts on websites. Two experiments (N=325, N=331) showed that the mere presence of advertisements with violent content on a simulated Facebook page induced higher levels of aggression-related cognition in comparison to non-violent adverts (d=0.56 , d=0.71). In a subsequent word recognition task, parti...

  12. The effects of exogenous fatty acids and niacin on human monocyte-macrophage plasticity.

    Science.gov (United States)

    Montserrat-de la Paz, Sergio; Rodriguez, Dolores; Cardelo, Magdalena P; Naranjo, Maria C; Bermudez, Beatriz; Abia, Rocio; Muriana, Francisco J G; Lopez, Sergio

    2017-08-01

    Macrophage plasticity allows adapting to different environments, having a dual activity in inflammatory-related diseases. Our hypothesis is that the type of dietary fatty acids into human postprandial triglyceride-rich lipoproteins (TRLs), alone or in combination with niacin (vitamin B3), could modulate the plasticity of monocytes-macrophages. We isolated TRLs at the postprandial peak from blood samples of healthy volunteers after the ingestion of a meal rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) or MUFAs plus omega-3 long-chain polyunsaturated fatty acids (LCPUFAs). Autologous monocytes isolated at fasting were first induced to differentiate into naïve macrophages. We observed that postprandial TRL-MUFAs, particularly in combination with niacin, enhance competence to monocytes to differentiate and polarise into M2 macrophages. Postprandial TRL-SFAs made polarised macrophages prone to an M1 phenotype. In contrast to dietary SFAs, dietary MUFAs in the meals plus immediate-release niacin primed circulating monocytes for a reduced postprandial pro-inflammatory profile. Our study underlines a role of postprandial TRLs as a metabolic entity in regulating the plasticity of the monocyte-macrophage lineage and also brings an understanding of the mechanisms by which dietary fatty acids are environmental factors fostering the innate immune responsiveness in humans. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. T Cell Zone Resident Macrophages Silently Dispose of Apoptotic Cells in the Lymph Node.

    Science.gov (United States)

    Baratin, Myriam; Simon, Léa; Jorquera, Audrey; Ghigo, Clément; Dembele, Doulaye; Nowak, Jonathan; Gentek, Rebecca; Wienert, Stephan; Klauschen, Frederick; Malissen, Bernard; Dalod, Marc; Bajénoff, Marc

    2017-08-15

    In lymph nodes (LNs), dendritic cells (DCs) are thought to dispose of apoptotic cells, a function pertaining to macrophages in other tissues. We found that a population of CX3CR1 + MERTK + cells located in the T cell zone of LNs, previously identified as DCs, are efferocytic macrophages. Lineage-tracing experiments and shield chimeras indicated that these T zone macrophages (TZM) are long-lived macrophages seeded in utero and slowly replaced by blood monocytes after birth. Imaging the LNs of mice in which TZM and DCs express different fluorescent proteins revealed that TZM-and not DCs-act as the only professional scavengers, clearing apoptotic cells in the LN T cell zone in a CX3CR1-dependent manner. Furthermore, similar to other macrophages, TZM appear inefficient in priming CD4 T cells. Thus, efferocytosis and T cell activation in the LN are uncoupled processes designated to macrophages and DCs, respectively, with implications to the maintenance of immune homeostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. French Prime Minister tours CERN

    CERN Multimedia

    Anaïs Schaeffer

    2012-01-01

    On 30 July, Jean-Marc Ayrault, the Prime Minister of the French Republic, and Geneviève Fioraso, the Minister of Higher Education and Research, visited the Laboratory.   After being met by the Director-General at LHC Point 5, they visited the CMS control centre and experiment cavern, and got a glimpse of the LHC tunnel at Point 5. The visit ended with a round-table discussion with French and other international members of CERN’s scientific community. During the discussion, the Prime Minister reaffirmed that “support for fundamental research has to be maintained, and France must continue to invest in education, research and innovation.” He also paid tribute to CERN's role in international cooperation, which he qualified as “a fine example of science without borders.”

  15. Priming motivation through unattended speech.

    Science.gov (United States)

    Radel, Rémi; Sarrazin, Philippe; Jehu, Marie; Pelletier, Luc

    2013-12-01

    This study examines whether motivation can be primed through unattended speech. Study 1 used a dichotic-listening paradigm and repeated strength measures. In comparison to the baseline condition, in which the unattended channel was only composed by neutral words, the presence of words related to high (low) intensity of motivation led participants to exert more (less) strength when squeezing a hand dynamometer. In a second study, a barely audible conversation was played while participants' attention was mobilized on a demanding task. Participants who were exposed to a conversation depicting intrinsic motivation performed better and persevered longer in a subsequent word-fragment completion task than those exposed to the same conversation made unintelligible. These findings suggest that motivation can be primed without attention. © 2013 The British Psychological Society.

  16. Z(prime) Phenomenology and the LHC

    International Nuclear Information System (INIS)

    Rizzo, Thomas G.

    2006-01-01

    A brief pedagogical overview of the phenomenology of Z(prime) gauge bosons is ILC in determining Z(prime) properties is also discussed. and explore in detail how the LHC may discover and help elucidate the models, review the current constraints on the possible properties of a Z(prime) nature of these new particles. We provide an overview of the Z(prime) studies presented. Such particles can arise in various electroweak extensions of that have been performed by both ATLAS and CMS. The role of the the Standard Model (SM). We provide a quick survey of a number of Z(prime)

  17. Recruiting and Retaining Cyberwarriors

    National Research Council Canada - National Science Library

    Westermeyer, Roger H

    2008-01-01

    .... Recruiting and retaining this highly skilled workforce is a significant challenge for the Air Force due to the high public and private sector demand for people with IT and related engineering skills...

  18. Recruiting and Retaining Cyberwarriors

    Science.gov (United States)

    2008-02-07

    2007 hearing of the House Oversight and Government Reform Subcommittee on Information Policy, Gregory Wilshusen, director of Information Technology at...Abbott Laboratories in Chicago, recruiters are reaching out to College students by offering flexible work schedules, telecommuting , full tuition

  19. Macrophages loaded with gold nanoshells for photothermal ablation of glioma: An in vitro model

    Science.gov (United States)

    Makkouk, Amani Riad

    The current median survival of patients with glioblastoma multiforme (GBM), the most common type of glioma, remains at 14.6 months despite multimodal treatments (surgery, radiotherapy and chemotherapy). This research aims to study the feasibility of photothermal ablation of glioma using gold nanoshells that are heated upon laser irradiation at their resonance wavelength. The novelty of our approach lies in improving nanoshell tumor delivery by loading them in macrophages, which are known to be recruited to gliomas via tumor-released chemoattractive agents. Ferumoxides, superparamagnetic iron oxide (SPIO) nanoparticles, are needed as an additional macrophage load in order to visualize macrophage accumulation in the tumor with magnetic resonance imaging (MRI) prior to laser irradiation. The feasibility of this approach was studied in an in vitro model of glioma spheroids with the use of continuous wave (CW) laser light for ablation. The optimal loading of both murine and rat macrophages with Ferumoxides was determined using inductively coupled plasma atomic emission spectroscopy (ICP-AES). Higher concentrations of SPIO were observed in rat macrophages, and the optimal concentration was chosen at 100 microg Fe/ml. Macrophages were found to be very sensitive to near infra-red (NIR) laser irradiation, and their use as vehicles was thus not expected to hinder the function of loaded nanoshells as tumor-ablating tools. The intracellular presence of gold nanoshells in macrophages was confirmed with TEM imaging. Next, the loading of both murine and rat macrophages with gold nanoshells was studied using UV/Vis spectrophotometry, where higher nanoshell uptake was found in rat macrophages. Incubation of loaded murine and rat macrophages with rat C-6 and human ACBT spheroids, respectively, resulted in their infiltration of the spheroids. Subsequent laser irradiation at 55 W/cm2 for 10 min and follow-up of spheroid average diameter size over 14 days post-irradiation showed that

  20. Nurse recruitment. Going places.

    Science.gov (United States)

    Buchan, James

    2002-08-01

    Overseas nurses account for 40 per cent of all new registrations in the UK and this may be rising to 50 per cent. This upward trend is likely to continue. International recruitment is to be part of the NHS's long-term strategy and is becoming the focus of increasing policy attention. The international labour market will become tighter: the US needs to recruit an extra million nurses of its own.

  1. Electronic Recruitment at CERN

    CERN Multimedia

    2004-01-01

    The Human Resources Department switches to electronic recruitment. From now on whenever you are involved in a recruitment action you will receive an e-mail giving you access to a Web folder. Inside you will find a shortlist of applications drawn up by the Human Resources Department. This will allow you to consult the folder, at the same time as everyone else involved in the recruitment process, for the vacancy you are interested in. This new electronic recruitment system, known as e-RT, will be introduced in a presentation given at 10 a.m. on 11 February in the Main Auditorium. Implemented by AIS (Administrative Information Services) and the Human Resources Department, e-RT will cover vacancies open in all of CERN's recruitment programmes. The electronic application system was initially made available to technical students in July 2003. By December it was extended to summer students, fellows, associates and Local Staff. Geraldine Ballet from the Recruitment Service prefers e-RT to mountains of paper! The Hu...

  2. The macrophage-histiocytic system

    Energy Technology Data Exchange (ETDEWEB)

    Cross, A

    1971-04-01

    The macrophage-histiocytic system is primarily concerned with the phagocytosis and degradation either of foreign material that enters the organism or of senile and damaged cells belonging to the organism itself. The system includes various kinds of cells with the common ability to process and eventually degrade and digest the ingested material. Two morphological characteristics of these cells are linked to their phagocytic functions: intra-cytoplasmic vacuoles and lysosomes. Although endothelial and fibroblastic cells can ingest particles, it seems that most cells of the macrophage-histiocytic system belong to the monocyte series. The stem cell of the system is still a matter for discussion and the mature cells have attracted a large and confusing array of names. Most of the experimental work with irradiation has involved macrophages of the peritoneal cavity and lymph nodes. It is likely that the other cells of the macrophage-histiocytic system are affected in the same way by irradiation, but this is not certain.

  3. Acquisition of repertoires of suppressor T cells under the influence of macrophages

    International Nuclear Information System (INIS)

    Soejima, T.; Nagayama, A.; Sado, T.; Taniguchi, M.

    1988-01-01

    Acquisition of repertoires and genetic restriction specificities of suppressor T cells (Ts) and their factors were studied by using full allogeneic radiation bone marrow chimera and H-2 congenic pairs, B10.A(3R) and B10.A(5R), which received conventional or cloned macrophages by cell transfer. Suppressor T-cell factor (TsF) from C3H----C57BL/6 or C57BL/6----C3H chimera suppressed only donor but not host-type responses of either C3H or C57BL/6, in an antigen-specific fashion. However, if chimera mice were given conventional or cloned macrophages of the host type, the chimera TsF in turn suppressed both the responses of C3H and C57BL/6 mice but not those of the third party, BALB/c, indicating that macrophages are responsible for the acquisition of host restriction specificity. Similarly, B10.A(5R) mice developed I-Jb restricted Ts or TsF when the B10.A(3R) macrophage cell line was injected at the time of antigen priming. The reverse was also true. B10.A(3R) mice did generate I-Jk restricted Ts when they received the B10.A(5R) macrophage cell line. Thus, the results clearly demonstrated that B10.A(3R) or B10.A(5R) mice potentially possessed their ability to express both I-Jk and I-Jb determinants and that repertoires and genetic restriction specificity of Ts and their TsF were acquired at a macrophage level at the time of antigen-priming

  4. FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in obesity.

    Science.gov (United States)

    Xiong, Xiao-Qing; Geng, Zhi; Zhou, Bing; Zhang, Feng; Han, Ying; Zhou, Ye-Bo; Wang, Jue-Jin; Gao, Xing-Ya; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2018-06-01

    Obesity-induced chronic inflammation is critical in the pathogenesis of insulin resistance, and the recruitment and proinflammatory activation of adipose tissue macrophages (ATMs) is important for the development of this process. Here, we examined the effects of fibronectin type III domain-containing 5 (FNDC5) on inflammation and insulin resistance in high-fat diet-induced obese mice. Male wild-type (WT) and FNDC5 -/- mice were fed with standard chow (Ctrl) or high fat diet (HFD) for 20 weeks to induce obesity and insulin resistance. Firstly, effects of FNDC5 gene deletion on obesity, insulin resistance, macrophage accumulation and polarization and adipose tissue inflammation were determined in mice. Secondly, the macrophage polarity shift was further examined with flow cytometry in isolated stromal vascular fraction (SVF). Thirdly, the effects of exogenous FNDC5 on lipopolysaccharide (LPS)-induced macrophage polarization, inflammation and the underlying signaling mechanism were investigated in RAW264.7 macrophages and primary mouse peritoneal cavity macrophages (PMs). Finally, the therapeutic effects of FNDC5 overexpression were examined in HFD-induced obese WT and FNDC5 -/- mice. FNDC5 gene deletion aggravated obesity, insulin resistance, fat accumulation and inflammation accompanied with enhanced AMPK inhibition, macrophages recruitment and M1 polarization in mice fed with HFD. Exogenous FNDC5 inhibited LPS-induced M1 macrophage polarization and inflammatory cytokine production via AMPK phosphorylation in both RAW264.7 macrophages and PMs. FNDC5 overexpression attenuated insulin resistance, AMPK inhibition, M1 macrophage polarization and inflammatory cytokine production in adipose tissue of obese WT and FNDC5 -/- mice. FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in HFD-induced obesity. FNDC5 plays several beneficial roles in obesity and may be used as a therapeutic regimen for preventing

  5. DMPD: The actions of bacterial DNA on murine macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10534106 The actions of bacterial DNA on murine macrophages. Sester DP, Stacey KJ, ... Show The actions of bacterial DNA on murine macrophages. PubmedID 10534106 Title The actions of bacterial DNA on murine macrophage

  6. Insights into the role of macrophage migration inhibitory factor in obesity and insulin resistance.

    LENUS (Irish Health Repository)

    Finucane, Orla M

    2012-11-01

    High-fat diet (HFD)-induced obesity has emerged as a state of chronic low-grade inflammation characterised by a progressive infiltration of immune cells, particularly macrophages, into obese adipose tissue. Adipose tissue macrophages (ATM) present immense plasticity. In early obesity, M2 anti-inflammatory macrophages acquire an M1 pro-inflammatory phenotype. Pro-inflammatory cytokines including TNF-α, IL-6 and IL-1β produced by M1 ATM exacerbate local inflammation promoting insulin resistance (IR), which consequently, can lead to type-2 diabetes mellitus (T2DM). However, the triggers responsible for ATM recruitment and activation are not fully understood. Adipose tissue-derived chemokines are significant players in driving ATM recruitment during obesity. Macrophage migration inhibitory factor (MIF), a chemokine-like inflammatory regulator, is enhanced during obesity and is directly associated with the degree of peripheral IR. This review focuses on the functional role of macrophages in obesity-induced IR and highlights the importance of the unique inflammatory cytokine MIF in propagating obesity-induced inflammation and IR. Given MIF chemotactic properties, MIF may be a primary candidate promoting ATM recruitment during obesity. Manipulating MIF inflammatory activities in obesity, using pharmacological agents or functional foods, may be therapeutically beneficial for the treatment and prevention of obesity-related metabolic diseases.

  7. Stroma cell priming in enteric lymphoid organ morphogenesis

    Directory of Open Access Journals (Sweden)

    Manuela eFerreira

    2012-07-01

    Full Text Available The lymphoid system is equipped with a network of specialized platforms located at strategic sites, which grant strict immune-surveillance and efficient immune responses. The development of these peripheral secondary lymphoid organs occurs mainly in utero, while tertiary lymphoid structures can form in adulthood generally in response to persistent infection and inflammation. Regardless of the lymphoid tissue and intrinsic cellular and molecular differences, it is now well established that the recruitment of fully functional Lymphoid Tissue inducer (LTi cells to presumptive lymphoid organ sites, and their consequent close and reciprocal interaction with resident stroma cells, are central to secondary lymphoid organ formation. In contrast, the nature of events that initially prime resident sessile stroma cells to recruit and retain LTi cells remains poorly understood.

  8. Visualisation of chicken macrophages using transgenic reporter genes: insights into the development of the avian macrophage lineage.

    Science.gov (United States)

    Balic, Adam; Garcia-Morales, Carla; Vervelde, Lonneke; Gilhooley, Hazel; Sherman, Adrian; Garceau, Valerie; Gutowska, Maria W; Burt, David W; Kaiser, Pete; Hume, David A; Sang, Helen M

    2014-08-01

    We have generated the first transgenic chickens in which reporter genes are expressed in a specific immune cell lineage, based upon control elements of the colony stimulating factor 1 receptor (CSF1R) locus. The Fms intronic regulatory element (FIRE) within CSF1R is shown to be highly conserved in amniotes and absolutely required for myeloid-restricted expression of fluorescent reporter genes. As in mammals, CSF1R-reporter genes were specifically expressed at high levels in cells of the macrophage lineage and at a much lower level in granulocytes. The cell lineage specificity of reporter gene expression was confirmed by demonstration of coincident expression with the endogenous CSF1R protein. In transgenic birds, expression of the reporter gene provided a defined marker for macrophage-lineage cells, identifying the earliest stages in the yolk sac, throughout embryonic development and in all adult tissues. The reporter genes permit detailed and dynamic visualisation of embryonic chicken macrophages. Chicken embryonic macrophages are not recruited to incisional wounds, but are able to recognise and phagocytose microbial antigens. © 2014. Published by The Company of Biologists Ltd.

  9. Wrath of God: religious primes and punishment.

    Science.gov (United States)

    McKay, Ryan; Efferson, Charles; Whitehouse, Harvey; Fehr, Ernst

    2011-06-22

    Recent evidence indicates that priming participants with religious concepts promotes prosocial sharing behaviour. In the present study, we investigated whether religious priming also promotes the costly punishment of unfair behaviour. A total of 304 participants played a punishment game. Before the punishment stage began, participants were subliminally primed with religion primes, secular punishment primes or control primes. We found that religious primes strongly increased the costly punishment of unfair behaviours for a subset of our participants--those who had previously donated to a religious organization. We discuss two proximate mechanisms potentially underpinning this effect. The first is a 'supernatural watcher' mechanism, whereby religious participants punish unfair behaviours when primed because they sense that not doing so will enrage or disappoint an observing supernatural agent. The second is a 'behavioural priming' mechanism, whereby religious primes activate cultural norms pertaining to fairness and its enforcement and occasion behaviour consistent with those norms. We conclude that our results are consistent with dual inheritance proposals about religion and cooperation, whereby religions harness the byproducts of genetically inherited cognitive mechanisms in ways that enhance the survival prospects of their adherents.

  10. Macrophage CGI-58 Attenuates Inflammatory Responsiveness via Promotion of PPARγ Signaling

    Directory of Open Access Journals (Sweden)

    Dan Yang

    2016-02-01

    Full Text Available Background/Aims: Comparative gene identification-58 (CGI-58, an adipose triglyceride lipase (ATGL coactivator, strongly promotes ATGL-mediated triglyceride (TG catabolism. Beyond its function in promoting lipolysis, other features of CGI-58 have been proposed. Here, we investigated the role of CGI-58 in the regulation of inflammatory responsiveness in macrophages. Methods: Macrophage-specific GCI-58 transgenic mice (TG and wild type mice (WT were fed a high fat diet (HFD, and RAW264.7 cells were treated with lipopolysaccharide (LPS. The peroxisome proliferator-activated receptor (PPAR signaling was detected. The inflammatory responsiveness and mitochondrial function were examined. Results: TG mice showed lower serum levels of proinflammatory cytokines and better mitochondrial function in macrophages compared with WT control. Knockdown of CGI-58 in RAW264.7 cells aggravated LPS-induced inflammation and mitochondrial dysfunction. CGI-58 overexpression and silencing in macrophages induced and inhibited PPARγ expression and activity, respectively. Most importantly, the PPARγ-specific agonist rosiglitazone significantly suppressed inflammation and mitochondrial dysfunction induced by CGI-58 deficiency. Furthermore, knockdown of PPARγ in macrophages significantly dampened the role of CGI-58 in suppression of inflammation and mitochondrial dysfunction. Interestingly, CGI-58 inhibited histone deacetylation and the recruitment of histone deacetylase (HDAC to the PPARγ promoter. Finally, ATGL deficiency did not affect inflammatory responsiveness and PPARγ signaling in macrophages. Conclusion: These results demonstrate that macrophage CGI-58 enhances PPARγ signaling and thus suppresses inflammatory responsiveness and mitochondrial dysfunction.

  11. Erythropoietin protects against rhabdomyolysis-induced acute kidney injury by modulating macrophage polarization

    Science.gov (United States)

    Wang, Shuo; Zhang, Chao; Li, Jiawei; Niyazi, Sidikejiang; Zheng, Long; Xu, Ming; Rong, Ruiming; Yang, Cheng; Zhu, Tongyu

    2017-01-01

    Erythropoietin (EPO) is a well-known hormone that is clinically used for the treatment of anemia. Very recently, an increasing body of evidence showed that EPO could still regulate bioactivities of macrophages. However, the details about the immunomodulatory effect of EPO on macrophages are not fully delineated, particularly in the setting of renal damages. Therefore, in the present study, we determined whether EPO could exert an impact on the dynamics of macrophages in a well-established model of rhabdomyolysis-induced acute kidney injury and explored the potential mechanisms. EPO was found to ameliorate kidney injuries by reducing macrophages recruitment and promoting phenotype switch toward M2 macrophages in vivo. It was also confirmed that EPO could directly suppress pro-inflammatory responses of M1 macrophages and promote M2 marker expression in vitro. Data indicated the possible involvement of Jak2/STAT3/STAT6 pathway in the augmentation of EPO on M2 polarization. These results improved the understanding of the immunoregulatory capacity of EPO on macrophages, which might optimize the therapeutic modalities of EPO. PMID:28383559

  12. Macrophage Depletion Attenuates Extracellular Matrix Deposition and Ductular Reaction in a Mouse Model of Chronic Cholangiopathies

    Science.gov (United States)

    Syn, Wing-Kin; Lagaisse, Kimberly; van Hul, Noemi; Heindryckx, Femke; Sowa, Jan-Peter; Peeters, Liesbeth; Van Vlierberghe, Hans; Leclercq, Isabelle A.; Canbay, Ali

    2016-01-01

    Chronic cholangiopathies, such as primary and secondary sclerosing cholangitis, are progressive disease entities, associated with periportal accumulation of inflammatory cells, encompassing monocytes and macrophages, peribiliary extracellular matrix (ECM) deposition and ductular reaction (DR). This study aimed to elucidate the relevance of macrophages in the progression of chronic cholangiopathies through macrophage depletion in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) mouse model. One group of mice received a single i.p. injection of Clodronate encapsulated liposomes (CLOLipo) at day 7 of a 14 day DDC treatment, while control animals were co-treated with PBSLipo instead. Mice were sacrificed after 7 or respectively 14 days of treatment for immunohistochemical assessment of macrophage recruitment (F4/80), ECM deposition (Sirius Red, Laminin) and DR (CK19). Macrophage depletion during a 14 day DDC treatment resulted in a significant inhibition of ECM deposition. Porto-lobular migration patterns of laminin-rich ECM and ductular structures were significantly attenuated and a progression of DR was effectively inhibited by macrophage depletion. CLOLipo co-treatment resulted in a confined DR to portal regions without amorphous cell clusters. This study suggests that therapeutic options selectively directed towards macrophages might represent a feasible treatment for chronic cholestatic liver diseases. PMID:27618307

  13. Novel Action of Carotenoids on Non-Alcoholic Fatty Liver Disease: Macrophage Polarization and Liver Homeostasis.

    Science.gov (United States)

    Ni, Yinhua; Zhuge, Fen; Nagashimada, Mayumi; Ota, Tsuguhito

    2016-06-24

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. It is characterized by a wide spectrum of hepatic changes, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is considered a hepatic manifestation of metabolic syndrome; however, mechanisms underlying the onset and progression of NAFLD are still unclear. Resident and recruited macrophages are key players in the homeostatic function of the liver and in the progression of NAFLD to NASH. Progress has been made in understanding the molecular mechanisms underlying the polarized activation of macrophages. New NAFLD therapies will likely involve modification of macrophage polarization by restraining M1 activation or driving M2 activation. Carotenoids are potent antioxidants and anti-inflammatory micronutrients that have been used to prevent and treat NAFLD. In addition to their antioxidative action, carotenoids can regulate macrophage polarization and thereby halt the progression of NASH. In this review, we summarize the molecular mechanisms of macrophage polarization and the function of liver macrophages/Kupffer cells in NAFLD. From our review, we propose that dietary carotenoids, such as β-cryptoxanthin and astaxanthin, be used to prevent or treat NAFLD through the regulation of macrophage polarization and liver homeostasis.

  14. Natural gas prime movers: A prime income opportunity?

    International Nuclear Information System (INIS)

    Katz, M.G.

    1997-01-01

    Although almost every factory, for example, uses compressed air to operate and control equipment--from power tools to packaging machinery--most air compressors are driven by electric motors. Similarly, although industry uses refrigeration for everything from freezing food to chilling warehouses to making chemicals and ice to operating skating rinks, natural gas powers only about 100 industrial refrigeration units in North America. But several factors are beginning to make natural gas more attractive as a prime mover. For one thing, the rising cost of electricity, with its demand or time-of-day and summer on-peak charges, has everyone looking for ways to cut their electric bills. At the same time, in the wake of deregulation of the nation's electric industry, customers can build on-site power plants that use natural gas to generate their own electricity, or have outside power suppliers or energy service companies (ESCOs) do it for them. Waste and exhaust heat, which can represent up to 60% of the total energy supplied from both engines and turbines, can be captured and used. Finally, growing concern over electric power outages has made natural gas more attractive for mission-critical operations, while new financing options let people buy and install natural gas prime movers more easily

  15. Lactoferricin Peptides Increase Macrophages' Capacity To Kill Mycobacterium avium.

    Science.gov (United States)

    Silva, Tânia; Moreira, Ana C; Nazmi, Kamran; Moniz, Tânia; Vale, Nuno; Rangel, Maria; Gomes, Paula; Bolscher, Jan G M; Rodrigues, Pedro N; Bastos, Margarida; Gomes, Maria Salomé

    2017-01-01

    Mycobacterial infections cause a significant burden of disease and death worldwide. Their treatment is long, toxic, costly, and increasingly prone to failure due to bacterial resistance to currently available antibiotics. New therapeutic options are thus clearly needed. Antimicrobial peptides represent an important source of new antimicrobial molecules, both for their direct activity and for their immunomodulatory potential. We have previously reported that a short version of the bovine antimicrobial peptide lactoferricin with amino acids 17 to 30 (LFcin17-30), along with its variants obtained by specific amino acid substitutions, killed Mycobacterium avium in broth culture. In the present work, those peptides were tested against M. avium living inside its natural host cell, the macrophage. We found that the peptides increased the antimicrobial action of the conventional antibiotic ethambutol inside macrophages. Moreover, the d-enantiomer of the lactoferricin peptide (d-LFcin17-30) was more stable and induced significant killing of intracellular mycobacteria by itself. Interestingly, d-LFcin17-30 did not localize to M. avium -harboring phagosomes but induced the production of proinflammatory cytokines and increased the formation of lysosomes and autophagosome-like vesicles. These results lead us to conclude that d-LFcin17-30 primes macrophages for intracellular microbial digestion through phagosomal maturation and/or autophagy, culminating in mycobacterial killing. IMPORTANCE The genus Mycobacterium comprises several pathogenic species, including M. tuberculosis , M. leprae , M. avium , etc. Infections caused by these bacteria are particularly difficult to treat due to their intrinsic impermeability, low growth rate, and intracellular localization. Antimicrobial peptides are increasingly acknowledged as potential treatment tools, as they have a high spectrum of activity, low tendency to induce bacterial resistance, and immunomodulatory properties. In this study, we

  16. The impact of splenectomy on human coronary artery atherosclerosis and vascular macrophage distribution.

    Science.gov (United States)

    Li, Yu; Stone, James R

    Splenectomy can potentially impact atherosclerosis through multiple mechanisms including altered lipid homeostasis, increased coagulation, and altered macrophage recruitment to the plaque. In patients, splenectomy has been associated with increased rates of coronary artery events, while in experimental mice, splenectomy causes increased atherosclerosis but reduces systemic monocyte supply. In this study, the direct impact of splenectomy on human coronary artery atherosclerotic plaque severity and macrophage content was investigated. Coronary artery atherosclerotic plaque severity was determined at autopsy in 18 long-term (≥10 years) splenectomy patients and 90 matched control patients. Coronary artery macrophage content was evaluated in mild atherosclerotic plaques of 11 mid- to long-term (≥1 year) splenectomy patients and 11 matched control patients. Splenectomy was associated with reduced coronary artery atherosclerosis (P=.03). The association was most pronounced for the subgroup of patients who had undergone splenectomy 20 years or more prior to death (P=.02). There was no difference in the density of macrophages in the plaque, media, or adventitia upon comparing splenectomy and control patients. In the control group, there was no correlation between the macrophage densities in the three arterial layers. However, in the splenectomy patients, there was a strong correlation in the macrophage densities across the plaque, media, and adventitia (P≤.0002), with resulting slopes that were significantly greater than seen in the control patients (P=.0007-.011). These findings indicate that, in humans, splenectomy is associated with lower coronary artery atherosclerotic plaque severity and altered coronary artery macrophage distribution. These results suggest that the spleen can modulate the recruitment of macrophages into human coronary arteries and the progression of atherosclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. VEGF-production by CCR2-dependent macrophages contributes to laser-induced choroidal neovascularization.

    Directory of Open Access Journals (Sweden)

    Torsten A Krause

    Full Text Available Age-related macular degeneration (AMD is the most prevalent cause of blindness in the elderly, and its exsudative subtype critically depends on local production of vascular endothelial growth factor A (VEGF. Mononuclear phagocytes, such as macrophages and microglia cells, can produce VEGF. Their precursors, for example monocytes, can be recruited to sites of inflammation by the chemokine receptor CCR2, and this has been proposed to be important in AMD. To investigate the role of macrophages and CCR2 in AMD, we studied intracellular VEGF content in a laser-induced murine model of choroidal neovascularisation. To this end, we established a technique to quantify the VEGF content in cell subsets from the laser-treated retina and choroid separately. 3 days after laser, macrophage numbers and their VEGF content were substantially elevated in the choroid. Macrophage accumulation was CCR2-dependent, indicating recruitment from the circulation. In the retina, microglia cells were the main VEGF+ phagocyte type. A greater proportion of microglia cells contained VEGF after laser, and this was CCR2-independent. On day 6, VEGF-expressing macrophage numbers had already declined, whereas numbers of VEGF+ microglia cells remained increased. Other sources of VEGF detectable by flow cytometry included in dendritic cells and endothelial cells in both retina and choroid, and Müller cells/astrocytes in the retina. However, their VEGF content was not increased after laser. When we analyzed flatmounts of laser-treated eyes, CCR2-deficient mice showed reduced neovascular areas after 2 weeks, but this difference was not evident 3 weeks after laser. In summary, CCR2-dependent influx of macrophages causes a transient VEGF increase in the choroid. However, macrophages augmented choroidal neovascularization only initially, presumably because VEGF production by CCR2-independent eye cells prevailed at later time points. These findings identify macrophages as a relevant source

  18. Innate immune response of alveolar macrophage to house dust mite allergen is mediated through TLR2/-4 co-activation.

    Directory of Open Access Journals (Sweden)

    Chia-Fang Liu

    Full Text Available House dust mite, Dermatophagoides pteronyssinus (Der p, is one of the major allergens responsible for allergic asthma. However, the putative receptors involved in the signalization of Der p to the innate immune cells are still poorly defined as well as the impact of their activation on the outcome of the allergen-induced cell response. We previously reported that the HDM activation of mouse alveolar macrophages (AM involves the TLR4/CD14 cell surface receptor complex. Here using a TLR ligand screening essay, we demonstrate that HDM protein extract engages the TLR2, in addition to the TLR4, in engineered TLR-transfected HEK cells but also in the MH-S mouse alveolar macrophage cell line model. Moreover we found that the concomitant recruitment of the MH-S cell's TLR2 and TLR4 receptors by the HDM extract activates the MyD88-dependent signaling pathway and leads to the secretion of the NF-κB regulated pro-inflammatory factors NO and TNF-α. However unlike with the canonical TLR4 ligand (i.e. the bacterial LPS mobilization of TLR4 by the HDM extract induces a reduced production of the IL-12 pro-inflammatory cytokine and fails to trigger the expression of the T-bet transcription factor. Finally we demonstrated that HDM extract down-regulates LPS induced IL-12 and T-bet expression through a TLR2 dependent mechanism. Therefore, we propose that the simultaneous engagement of the TLR2 and TLR4 receptors by the HDM extract results in a cross regulated original activation pattern of the AM which may contribute to the Th2 polarization of the allergen-induced immune response. The deciphering of these cross-regulation networks is of prime importance to open the way for original therapeutic strategies taking advantage of these receptors and their associated signaling pathways to treat allergic asthma.

  19. Imaging of macrophage-related lung diseases

    International Nuclear Information System (INIS)

    Marten, Katharina; Hansell, David M.

    2005-01-01

    Macrophage-related pulmonary diseases are a heterogeneous group of disorders characterized by macrophage accumulation, activation or dysfunction. These conditions include smoking-related interstitial lung diseases, metabolic disorders such as Niemann-Pick or Gaucher disease, and rare primary lung tumors. High-resolution computed tomography abnormalities include pulmonary ground-glass opacification secondary to infiltration by macrophages, centrilobular nodules or interlobular septal thickening reflecting peribronchiolar or septal macrophage accumulation, respectively, emphysema caused by macrophage dysfunction, and honeycombing following macrophage-related lung matrix remodeling. (orig.)

  20. Priming of antiherbivore defensive responses in plants

    Institute of Scientific and Technical Information of China (English)

    Jinwon Kim; Gary W.Felton

    2013-01-01

    Defense priming is defined as increased readiness of defense induction.A growing body of literature indicates that plants (or intact parts of a plant) are primed in anticipation of impending environmental stresses,both biotic and abiotic,and upon the following stimulus,induce defenses more quickly and strongly.For instance,some plants previously exposed to herbivore-inducible plant volatiles (HIPVs) from neighboring plants under herbivore attack show faster or stronger defense activation and enhanced insect resistance when challenged with secondary insect feeding.Research on priming of antiherbivore defense has been limited to the HIPV-mediated mechanism until recently,but significant advances were made in the past three years,including non-HIPV-mediated defense priming,epigenetic modifications as the molecular mechanism of priming,and others.It is timely to consider the advances in research on defense priming in the plantinsect interactions.

  1. The effect of priming with a love concept on blood donation promise.

    Science.gov (United States)

    Charles-Sire, Virginie; Guéguen, Nicolas; Meineri, Sébastien; Martin, Angélique; Bullock, Andrea

    2014-02-01

    This field study on blood donor behavior tests the effectiveness of semantic priming on donor intention and commitment. Using face-to-face interactions, participants were primed with the concept of love and solicited to promise blood to the French National Blood Bank. Results showed a significant effect on willingness to donate blood and on donor commitment. The relatively simple and easily implemented technique used in this study could be of interest in improving performance of recruitment and retention campaigns. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Sales Force Recruitment

    OpenAIRE

    Flaviu MEGHISAN

    2008-01-01

    The sales plan is put into practice through the tasks associated with sales plan implementation. Whereas sales plan formulation focuses on "doing the right things," implementation emphasizes "doing things right." The three major tasks involved in implementing a sales plan are (1) salesforce recruitment and selection, (2) salesforce training, and (3) salesforce motivation and compensation.

  3. Recruitment and Retention.

    Science.gov (United States)

    Combs, Jolene

    1986-01-01

    Suggests ways community college journalism instructors can recruit and retain students in journalism classes (e.g., host a high school press day, fund a journalism scholarship, sponsor events for high school journalism teachers and advisers, serve as counselor for journalism majors, have a yearly journalism convocation, and involve campus…

  4. E-recruitment

    DEFF Research Database (Denmark)

    Holm, Anna B.

    2012-01-01

    tasks and subtasks. For management, the main task is now that of communicating with candidates. In addition, a new on-going task of maintaining a corporate career website has become an integral part of the new recruitment process. The new design is presented in the following, and its implications...

  5. Bilateral robotic priming before task-oriented approach in subacute stroke rehabilitation: a pilot randomized controlled trial.

    Science.gov (United States)

    Hsieh, Yu-Wei; Wu, Ching-Yi; Wang, Wei-En; Lin, Keh-Chung; Chang, Ku-Chou; Chen, Chih-Chi; Liu, Chien-Ting

    2017-02-01

    To investigate the treatment effects of bilateral robotic priming combined with the task-oriented approach on motor impairment, disability, daily function, and quality of life in patients with subacute stroke. A randomized controlled trial. Occupational therapy clinics in medical centers. Thirty-one subacute stroke patients were recruited. Participants were randomly assigned to receive bilateral priming combined with the task-oriented approach (i.e., primed group) or to the task-oriented approach alone (i.e., unprimed group) for 90 minutes/day, 5 days/week for 4 weeks. The primed group began with the bilateral priming technique by using a bimanual robot-aided device. Motor impairments were assessed by the Fugal-Meyer Assessment, grip strength, and the Box and Block Test. Disability and daily function were measured by the modified Rankin Scale, the Functional Independence Measure, and actigraphy. Quality of life was examined by the Stroke Impact Scale. The primed and unprimed groups improved significantly on most outcomes over time. The primed group demonstrated significantly better improvement on the Stroke Impact Scale strength subscale ( p = 0.012) and a trend for greater improvement on the modified Rankin Scale ( p = 0.065) than the unprimed group. Bilateral priming combined with the task-oriented approach elicited more improvements in self-reported strength and disability degrees than the task-oriented approach by itself. Further large-scale research with at least 31 participants in each intervention group is suggested to confirm the study findings.

  6. Can Faces Prime a Language?

    Science.gov (United States)

    Woumans, Evy; Martin, Clara D; Vanden Bulcke, Charlotte; Van Assche, Eva; Costa, Albert; Hartsuiker, Robert J; Duyck, Wouter

    2015-09-01

    Bilinguals have two languages that are activated in parallel. During speech production, one of these languages must be selected on the basis of some cue. The present study investigated whether the face of an interlocutor can serve as such a cue. Spanish-Catalan and Dutch-French bilinguals were first familiarized with certain faces, each of which was associated with only one language, during simulated Skype conversations. Afterward, these participants performed a language production task in which they generated words associated with the words produced by familiar and unfamiliar faces displayed on-screen. When responding to familiar faces, participants produced words faster if the faces were speaking the same language as in the previous Skype simulation than if the same faces were speaking a different language. Furthermore, this language priming effect disappeared when it became clear that the interlocutors were actually bilingual. These findings suggest that faces can prime a language, but their cuing effect disappears when it turns out that they are unreliable as language cues. © The Author(s) 2015.

  7. Complex architecture of primes and natural numbers.

    Science.gov (United States)

    García-Pérez, Guillermo; Serrano, M Ángeles; Boguñá, Marián

    2014-08-01

    Natural numbers can be divided in two nonoverlapping infinite sets, primes and composites, with composites factorizing into primes. Despite their apparent simplicity, the elucidation of the architecture of natural numbers with primes as building blocks remains elusive. Here, we propose a new approach to decoding the architecture of natural numbers based on complex networks and stochastic processes theory. We introduce a parameter-free non-Markovian dynamical model that naturally generates random primes and their relation with composite numbers with remarkable accuracy. Our model satisfies the prime number theorem as an emerging property and a refined version of Cramér's conjecture about the statistics of gaps between consecutive primes that seems closer to reality than the original Cramér's version. Regarding composites, the model helps us to derive the prime factors counting function, giving the probability of distinct prime factors for any integer. Probabilistic models like ours can help to get deeper insights about primes and the complex architecture of natural numbers.

  8. eHealth Recruitment Challenges

    Science.gov (United States)

    Thompson, Debbe; Canada, Ashanti; Bhatt, Riddhi; Davis, Jennifer; Plesko, Lisa; Baranowski, Tom; Cullen, Karen; Zakeri, Issa

    2006-01-01

    Little is known about effective eHealth recruitment methods. This paper presents recruitment challenges associated with enrolling African-American girls aged 8-10 years in an eHealth obesity prevention program, their effect on the recruitment plan, and potential implications for eHealth research. Although the initial recruitment strategy was…

  9. Priming within and across modalities: exploring the nature of rCBF increases and decreases.

    Science.gov (United States)

    Badgaiyan, R D; Schacter, D L; Alpert, N M

    2001-02-01

    Neuroimaging studies suggest that within-modality priming is associated with reduced regional cerebral blood flow (rCBF) in the extrastriate area, whereas cross-modality priming is associated with increased rCBF in prefrontal cortex. To characterize the nature of rCBF changes in within- and cross-modality priming, we conducted two neuroimaging experiments using positron emission tomography (PET). In experiment 1, rCBF changes in within-modality auditory priming on a word stem completion task were observed under same- and different-voice conditions. Both conditions were associated with decreased rCBF in extrastriate cortex. In the different-voice condition there were additional rCBF changes in the middle temporal gyrus and prefrontal cortex. Results suggest that the extrastriate involvement in within-modality priming is sensitive to a change in sensory modality of target stimuli between study and test, but not to a change in the feature of a stimulus within the same modality. In experiment 2, we studied cross-modality priming on a visual stem completion test after encoding under full- and divided-attention conditions. Increased rCBF in the anterior prefrontal cortex was observed in the full- but not in the divided-attention condition. Because explicit retrieval is compromised after encoding under the divided-attention condition, prefrontal involvement in cross-modality priming indicates recruitment of an aspect of explicit retrieval mechanism. The aspect of explicit retrieval that is most likely to be involved in cross-modality priming is the familiarity effect. Copyright 2001 Academic Press.

  10. Priming in concert: Assimilation and contrast with multiple affective and gender primes.

    NARCIS (Netherlands)

    Fockenberg, D.A.; Koole, S.L.; Semin, G.R.

    2008-01-01

    The present research investigated the influence of multiple sequential primes on social categorization processes. Study 1 examined an evaluative decision task in which targets were preceded and succeeded by two primes. As expected, the temporally closest forward primes had assimilative effects on

  11. Unconscious Congruency Priming from Unpracticed Words Is Modulated by Prime-Target Semantic Relatedness

    Science.gov (United States)

    Ortells, Juan J.; Mari-Beffa, Paloma; Plaza-Ayllon, Vanesa

    2013-01-01

    Participants performed a 2-choice categorization task on visible word targets that were preceded by novel (unpracticed) prime words. The prime words were presented for 33 ms and followed either immediately (Experiments 1-3) or after a variable delay (Experiments 1 and 4) by a pattern mask. Both subjective and objective measures of prime visibility…

  12. IAP survivin regulates atherosclerotic macrophage survival

    NARCIS (Netherlands)

    Blanc-Brude, Olivier P.; Teissier, Elisabeth; Castier, Yves; Lesèche, Guy; Bijnens, Ann-Pascal; Daemen, Mat; Staels, Bart; Mallat, Ziad; Tedgui, Alain

    2007-01-01

    Inflammatory macrophage apoptosis is critical to atherosclerotic plaque formation, but its mechanisms remain enigmatic. We hypothesized that inhibitor of apoptosis protein (IAP) survivin regulates macrophage death in atherosclerosis. Western blot analysis revealed discrete survivin expression in

  13. Priming of innate antimycobacterial immunity by heat-killed Listeria monocytogenes induces sterilizing response in the adult zebrafish tuberculosis model

    Directory of Open Access Journals (Sweden)

    Hanna Luukinen

    2018-01-01

    Full Text Available Mycobacterium tuberculosis remains one of the most problematic infectious agents, owing to its highly developed mechanisms to evade host immune responses combined with the increasing emergence of antibiotic resistance. Host-directed therapies aiming to optimize immune responses to improve bacterial eradication or to limit excessive inflammation are a new strategy for the treatment of tuberculosis. In this study, we have established a zebrafish-Mycobacterium marinum natural host-pathogen model system to study induced protective immune responses in mycobacterial infection. We show that priming adult zebrafish with heat-killed Listeria monocytogenes (HKLm at 1 day prior to M. marinum infection leads to significantly decreased mycobacterial loads in the infected zebrafish. Using rag1−/− fish, we show that the protective immunity conferred by HKLm priming can be induced through innate immunity alone. At 24 h post-infection, HKLm priming leads to a significant increase in the expression levels of macrophage-expressed gene 1 (mpeg1, tumor necrosis factor α (tnfa and nitric oxide synthase 2b (nos2b, whereas superoxide dismutase 2 (sod2 expression is downregulated, implying that HKLm priming increases the number of macrophages and boosts intracellular killing mechanisms. The protective effects of HKLm are abolished when the injected material is pretreated with nucleases or proteinase K. Importantly, HKLm priming significantly increases the frequency of clearance of M. marinum infection by evoking sterilizing immunity (25 vs 3.7%, P=0.0021. In this study, immune priming is successfully used to induce sterilizing immunity against mycobacterial infection. This model provides a promising new platform for elucidating the mechanisms underlying sterilizing immunity and to develop host-directed treatment or prevention strategies against tuberculosis. This article has an associated First Person interview with the first author of the paper.

  14. Stacking faults of {gamma}{prime}{prime} phase precipitated in a Ni-15Cr-8Fe-6Nb alloy; Ni-15Cr-8Fe-6Nb gokin ni sekishutsusuru {gamma}{prime}{prime} sonai no sekiso kekkan

    Energy Technology Data Exchange (ETDEWEB)

    Kusabiraki, K; Ikeuchi, S [Toyama University, Toyama (Japan). Faculty of Engineering

    1995-09-01

    The stacking faults of a metastable {gamma}{prime}{prime} phase precipitated in a nickel-base superalloy, a modified NCF 3 type alloy (X-750M) were investigated by transmission electron microscopy and X-ray diffraction method. The {gamma}{prime}{prime} precipitates are circular shaped plates at the early stage of aging and they become elliptic or irregular shaped plates at the latter stage of aging up to 1033K. Contrast which suggests the existence of stacking faults on {l_brace}112{r_brace}{sub {gamma}{prime}{prime}} planes can be seen in many of large {gamma}{prime}{prime} precipitates extracted from the specimens aged at 1033K. It is clear that the values of {gamma}{prime}{prime}/{gamma} lattice mismatch increase with increasing the aging time from the measurement of lattice constants of the {gamma} and the {gamma}{prime}{prime} phase. The formation of stacking faults on {l_brace}112{r_brace}{sub {gamma}{prime}{prime}} in the large {gamma}{prime}{prime} precipitates is due to the movement of an a/6 [111] partial dislocation introduced by {gamma}{prime}{prime} /{gamma} coherency strain. Since a part of stacking sequence has a similar crystal structure to that of a stable {delta} phase precipitates in {gamma} phase, the formation of stacking faults in the {gamma}{prime}{prime} precipitates is considered to be favorable for the stabilization of them. 14 refs., 10 figs., 1 tab.

  15. Role of Osteal Macrophages in Bone Metabolism

    Directory of Open Access Journals (Sweden)

    Sun Wook Cho

    2015-03-01

    Full Text Available Macrophages have been shown to have pleiotropic functions in various pathophysiologies, especially in terms of anti-inflammatory and regenerative activity. Recently, the novel functions of bone marrow resident macrophages (called osteal macrophages were intensively studied in bone development, remodeling and tissue repair processes. This review discusses the current evidence for a role of osteal macrophages in bone modeling, remodeling, and fracture healing processes.

  16. Additive theory of prime numbers

    CERN Document Server

    Hua, L K

    2009-01-01

    Loo-Keng Hua was a master mathematician, best known for his work using analytic methods in number theory. In particular, Hua is remembered for his contributions to Waring's Problem and his estimates of trigonometric sums. Additive Theory of Prime Numbers is an exposition of the classic methods as well as Hua's own techniques, many of which have now also become classic. An essential starting point is Vinogradov's mean-value theorem for trigonometric sums, which Hua usefully rephrases and improves. Hua states a generalized version of the Waring-Goldbach problem and gives asymptotic formulas for the number of solutions in Waring's Problem when the monomial x^k is replaced by an arbitrary polynomial of degree k. The book is an excellent entry point for readers interested in additive number theory. It will also be of value to those interested in the development of the now classic methods of the subject.

  17. Can False Memories Prime Problem Solutions?

    Science.gov (United States)

    Howe, Mark L.; Garner, Sarah R.; Dewhurst, Stephen A.; Ball, Linden J.

    2010-01-01

    Previous research has suggested that false memories can prime performance on related implicit and explicit memory tasks. The present research examined whether false memories can also be used to prime higher order cognitive processes, namely, insight-based problem solving. Participants were asked to solve a number of compound remote associate task…

  18. Visual Priming of Inverted and Rotated Objects

    Science.gov (United States)

    Knowlton, Barbara J.; McAuliffe, Sean P.; Coelho, Chase J.; Hummel, John E.

    2009-01-01

    Object images are identified more efficiently after prior exposure. Here, the authors investigated shape representations supporting object priming. The dependent measure in all experiments was the minimum exposure duration required to correctly identify an object image in a rapid serial visual presentation stream. Priming was defined as the change…

  19. Syntactic priming in American Sign Language.

    Science.gov (United States)

    Hall, Matthew L; Ferreira, Victor S; Mayberry, Rachel I

    2015-01-01

    Psycholinguistic studies of sign language processing provide valuable opportunities to assess whether language phenomena, which are primarily studied in spoken language, are fundamentally shaped by peripheral biology. For example, we know that when given a choice between two syntactically permissible ways to express the same proposition, speakers tend to choose structures that were recently used, a phenomenon known as syntactic priming. Here, we report two experiments testing syntactic priming of a noun phrase construction in American Sign Language (ASL). Experiment 1 shows that second language (L2) signers with normal hearing exhibit syntactic priming in ASL and that priming is stronger when the head noun is repeated between prime and target (the lexical boost effect). Experiment 2 shows that syntactic priming is equally strong among deaf native L1 signers, deaf late L1 learners, and hearing L2 signers. Experiment 2 also tested for, but did not find evidence of, phonological or semantic boosts to syntactic priming in ASL. These results show that despite the profound differences between spoken and signed languages in terms of how they are produced and perceived, the psychological representation of sentence structure (as assessed by syntactic priming) operates similarly in sign and speech.

  20. Negative Priming in Free Recall Reconsidered

    Science.gov (United States)

    Hanczakowski, Maciej; Beaman, C. Philip; Jones, Dylan M.

    2016-01-01

    Negative priming in free recall is the finding of impaired memory performance when previously ignored auditory distracters become targets of encoding and retrieval. This negative priming has been attributed to an aftereffect of deploying inhibitory mechanisms that serve to suppress auditory distraction and minimize interference with learning and…

  1. Syntactic priming in American Sign Language.

    Directory of Open Access Journals (Sweden)

    Matthew L Hall

    Full Text Available Psycholinguistic studies of sign language processing provide valuable opportunities to assess whether language phenomena, which are primarily studied in spoken language, are fundamentally shaped by peripheral biology. For example, we know that when given a choice between two syntactically permissible ways to express the same proposition, speakers tend to choose structures that were recently used, a phenomenon known as syntactic priming. Here, we report two experiments testing syntactic priming of a noun phrase construction in American Sign Language (ASL. Experiment 1 shows that second language (L2 signers with normal hearing exhibit syntactic priming in ASL and that priming is stronger when the head noun is repeated between prime and target (the lexical boost effect. Experiment 2 shows that syntactic priming is equally strong among deaf native L1 signers, deaf late L1 learners, and hearing L2 signers. Experiment 2 also tested for, but did not find evidence of, phonological or semantic boosts to syntactic priming in ASL. These results show that despite the profound differences between spoken and signed languages in terms of how they are produced and perceived, the psychological representation of sentence structure (as assessed by syntactic priming operates similarly in sign and speech.

  2. Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo.

    Science.gov (United States)

    Iqbal, Asif J; McNeill, Eileen; Kapellos, Theodore S; Regan-Komito, Daniel; Norman, Sophie; Burd, Sarah; Smart, Nicola; Machemer, Daniel E W; Stylianou, Elena; McShane, Helen; Channon, Keith M; Chawla, Ajay; Greaves, David R

    2014-10-09

    The recruitment of monocytes and their differentiation into macrophages at sites of inflammation are key events in determining the outcome of the inflammatory response and initiating the return to tissue homeostasis. To study monocyte trafficking and macrophage differentiation in vivo, we have generated a novel transgenic reporter mouse expressing a green fluorescent protein (GFP) under the control of the human CD68 promoter. CD68-GFP mice express high levels of GFP in both monocyte and embryo-derived tissue resident macrophages in adult animals. The human CD68 promoter drives GFP expression in all CD115(+) monocytes of adult blood, spleen, and bone marrow; we took advantage of this to directly compare the trafficking of bone marrow-derived CD68-GFP monocytes to that of CX3CR1(GFP) monocytes in vivo using a sterile zymosan peritonitis model. Unlike CX3CR1(GFP) monocytes, which downregulate GFP expression on differentiation into macrophages in this model, CD68-GFP monocytes retain high-level GFP expression for 72 hours after differentiation into macrophages, allowing continued cell tracking during resolution of inflammation. In summary, this novel CD68-GFP transgenic reporter mouse line represents a powerful resource for analyzing monocyte mobilization and monocyte trafficking as well as studying the fate of recruited monocytes in models of acute and chronic inflammation. © 2014 by The American Society of Hematology.

  3. Adipocytes and Macrophages Interplay in the Orchestration of Tumor Microenvironment: New Implications in Cancer Progression

    Directory of Open Access Journals (Sweden)

    Luís Henrique Corrêa

    2017-09-01

    Full Text Available Inflammation has been known as one of the main keys to the establishment and progression of cancers. Chronic low-grade inflammation is also a strategic condition that underlies the causes and development of metabolic syndrome and obesity. Moreover, obesity has been largely related to poor prognosis of tumors by modulating tumor microenvironment with secretion of several inflammatory mediators by tumor-associated adipocytes (TAAs, which can modulate and recruit tumor-associated macrophages. Thus, the understanding of cellular and molecular mechanisms that underlay and link inflammation, obesity, and cancer is crucial to identify potential targets that interfere with this important route. Knowledge about the exact role of each component of the tumor microenvironment is not yet fully understood, but the new insights in literature highlight the essential role of adipocytes and macrophages interplay as key factor to determine the fate of cancer progression. In this review article, we focus on the functions of adipocytes and macrophages orchestrating cellular and molecular mechanisms that lead to inflammatory modulation in tumor microenvironment, which will be crucial to cancer establishment. We also emphasized the mechanisms by which the tumor promotes itself by recruiting and polarizing macrophages, discussing the role of adipocytes in this process. In addition, we discuss here the newest possible anticancer therapeutic treatments aiming to retard the development of the tumor based on what is known about cancer, adipocyte, and macrophage polarization.

  4. Suppression of annexin A2 by prostaglandin E₂ impairs phagocytic ability of peritoneal macrophages in women with endometriosis.

    Science.gov (United States)

    Wu, Meng-Hsing; Chuang, Pei-Chin; Lin, Yiu-Juian; Tsai, Shaw-Jenq

    2013-04-01

    Is annexin A2 involved in the reduced phagocytic ability of macrophages in endometriosis? Data from women with endometriosis and a murine model of the disease show that expression of annexin A2 in peritoneal macrophages is inhibited by prostaglandin E2 (PGE2) and this impairs the phagocytic ability of macrophages. Endometriosis is a chronic inflammatory disease that recruits many immune cells, especially macrophages, to the peritoneal cavity. The phagocytic ability of peritoneal macrophages isolated from women with endometriosis is reduced. A laboratory study. Thirty-five patients (20 with and 15 without endometriosis) of reproductive age with normal menstrual cycles were recruited. Peritoneal macrophages isolated from women with or without endometriosis were cultured and treated with vehicle, PGE2 and different EP receptor agonists, and the expression of annexin A2 was quantified by RT-PCR and western blotting. Annexin A2 was knocked down (by small interfering RNA) in normal macrophages or overexpressed (by treatment with recombinant protein) in endometriotic macrophages and their phagocytic ability was measured by flow cytometry. Peritoneal macrophages were isolated from a mouse model of endometriosis and treated with PGE2 or cyclo-oxygenase (COX) inhibitors, and annexin A2 mRNA was quantified. Levels of annexin A2 were markedly reduced in peritoneal macrophages from women with endometriosis versus controls (mRNA: P endometriosis versus control) via the EP2/EP4 receptor-dependent signaling pathway. Treatment with PGE2 or knockdown of annexin A2 inhibited the phagocytic ability of macrophages (P peritoneal macrophages were markedly reduced in mice treated with PGE2 (P peritoneal macrophages (P peritoneal cells from patients with endometriosis or that their endometriotic fluid contains increased amounts of PGE2 when compared with control subjects. Inhibiting PGE2 signaling, in order to restore or enhance the phagocytic capability of macrophages, may represent a new

  5. Object color affects identification and repetition priming.

    Science.gov (United States)

    Uttl, Bob; Graf, Peter; Santacruz, Pilar

    2006-10-01

    We investigated the influence of color on the identification of both non-studied and studied objects. Participants studied black and white and color photos of common objects and memory was assessed with an identification test. Consistent with our meta-analysis of prior research, we found that objects were easier to identify from color than from black and white photos. We also found substantial priming in all conditions, and study-to-test changes in an object's color reduced the magnitude of priming. Color-specific priming effects were large for color-complex objects, but minimal for color-simple objects. The pattern and magnitude of priming effects was not influenced either by the extent to which an object always appears in the same color (i.e., whether a color is symptomatic of an object) or by the object's origin (natural versus fabricated). We discuss the implications of our findings for theoretical accounts of object perception and repetition priming.

  6. Lexical priming in Alzheimer's disease and aphasia.

    Science.gov (United States)

    Arroyo-Anlló, Eva Maria; Beauchamps, Mireille; Ingrand, Pierre; Neau, Jean Philippe; Gil, Roger

    2013-01-01

    Lexical priming was examined in patients with Alzheimer's disease and in aphasic patients. Control participants were divided into young and elderly [cf. Arroyo-Anlló et al.: Eur J Cogn Psychol 2004;16:535-553]. For lexical priming, a word-stem completion task was used. Normal elderly participants had lexical priming scores that were significantly lower than those of young individuals. Analysis of covariance with age and educational level as covariates showed that the control participants, aphasic and Alzheimer patients did not differ significantly on the lexical priming task. Our results suggest that performance in the lexical priming task diminishes with physiological aging, but is not significantly affected by mild or moderate Alzheimer's disease or by fluent or non-fluent aphasia. Copyright © 2013 S. Karger AG, Basel.

  7. Priming analogical reasoning with false memories.

    Science.gov (United States)

    Howe, Mark L; Garner, Sarah R; Threadgold, Emma; Ball, Linden J

    2015-08-01

    Like true memories, false memories are capable of priming answers to insight-based problems. Recent research has attempted to extend this paradigm to more advanced problem-solving tasks, including those involving verbal analogical reasoning. However, these experiments are constrained inasmuch as problem solutions could be generated via spreading activation mechanisms (much like false memories themselves) rather than using complex reasoning processes. In three experiments we examined false memory priming of complex analogical reasoning tasks in the absence of simple semantic associations. In Experiment 1, we demonstrated the robustness of false memory priming in analogical reasoning when backward associative strength among the problem terms was eliminated. In Experiments 2a and 2b, we extended these findings by demonstrating priming on newly created homonym analogies that can only be solved by inhibiting semantic associations within the analogy. Overall, the findings of the present experiments provide evidence that the efficacy of false memory priming extends to complex analogical reasoning problems.

  8. HIV-1 and the macrophage

    NARCIS (Netherlands)

    Bol, Sebastiaan M.; Cobos-Jimenez, Viviana; Kootstra, Neeltje A.; van 't Wout, Angelique B.

    2011-01-01

    Macrophages and CD4(+) T cells are natural target cells for HIV-1, and both cell types contribute to the establishment of the viral reservoir that is responsible for continuous residual virus replication during antiretroviral therapy and viral load rebound upon treatment interruption. Scientific

  9. Silencing CCR2 in Macrophages Alleviates Adipose Tissue Inflammation and the Associated Metabolic Syndrome in Dietary Obese Mice.

    Science.gov (United States)

    Kim, Jongkil; Chung, Kunho; Choi, Changseon; Beloor, Jagadish; Ullah, Irfan; Kim, Nahyeon; Lee, Kuen Yong; Lee, Sang-Kyung; Kumar, Priti

    2016-01-26

    Adipose tissue macrophage (ATM)-mediated inflammation is a key feature contributing to the adverse metabolic outcomes of dietary obesity. Recruitment of macrophages to obese adipose tissues (AT) can occur through the engagement of CCR2, the receptor for MCP-1 (monocyte chemoattractant protein-1), which is expressed on peripheral monocytes/macrophages. Here, we show that i.p. administration of a rabies virus glycoprotein-derived acetylcholine receptor-binding peptide effectively delivers complexed siRNA into peritoneal macrophages and ATMs in a mouse model of high-fat diet-induced obesity. Treatment with siRNA against CCR2 inhibited macrophage infiltration and accumulation in AT and, therefore, proinflammatory cytokines produced by macrophages. Consequently, the treatment significantly improved glucose tolerance and insulin sensitivity profiles, and also alleviated the associated symptoms of hepatic steatosis and reduced hepatic triglyceride production. These results demonstrate that disruption of macrophage chemotaxis to the AT through cell-targeted gene knockdown strategies can provide a therapeutic intervention for obesity-related metabolic diseases. The study also highlights a siRNA delivery approach for targeting specific monocyte subsets that contribute to obesity-associated inflammation without affecting the function of other tissue-resident macrophages that are essential for host homeostasis and survival.

  10. Silencing CCR2 in Macrophages Alleviates Adipose Tissue Inflammation and the Associated Metabolic Syndrome in Dietary Obese Mice

    Directory of Open Access Journals (Sweden)

    Jongkil Kim

    2016-01-01

    Full Text Available Adipose tissue macrophage (ATM-mediated inflammation is a key feature contributing to the adverse metabolic outcomes of dietary obesity. Recruitment of macrophages to obese adipose tissues (AT can occur through the engagement of CCR2, the receptor for MCP-1 (monocyte chemoattractant protein-1, which is expressed on peripheral monocytes/macrophages. Here, we show that i.p. administration of a rabies virus glycoprotein-derived acetylcholine receptor-binding peptide effectively delivers complexed siRNA into peritoneal macrophages and ATMs in a mouse model of high-fat diet-induced obesity. Treatment with siRNA against CCR2 inhibited macrophage infiltration and accumulation in AT and, therefore, proinflammatory cytokines produced by macrophages. Consequently, the treatment significantly improved glucose tolerance and insulin sensitivity profiles, and also alleviated the associated symptoms of hepatic steatosis and reduced hepatic triglyceride production. These results demonstrate that disruption of macrophage chemotaxis to the AT through cell-targeted gene knockdown strategies can provide a therapeutic intervention for obesity-related metabolic diseases. The study also highlights a siRNA delivery approach for targeting specific monocyte subsets that contribute to obesity-associated inflammation without affecting the function of other tissue-resident macrophages that are essential for host homeostasis and survival.

  11. False memories and lexical decision: even twelve primes do not cause long-term semantic priming.

    Science.gov (United States)

    Zeelenberg, René; Pecher, Diane

    2002-03-01

    Semantic priming effects are usually obtained only if the prime is presented shortly before the target stimulus. Recent evidence obtained with the so-called false memory paradigm suggests, however, that in both explicit and implicit memory tasks semantic relations between words can result in long-lasting effects when multiple 'primes' are presented. The aim of the present study was to investigate whether these effects would generalize to lexical decision. In four experiments we showed that even as many as 12 primes do not cause long-term semantic priming. In all experiments, however, a repetition priming effect was obtained. The present results are consistent with a number of other results showing that semantic information plays a minimal role in long-term priming in visual word recognition.

  12. Carbon black nanoparticles induce type II epithelial cells to release chemotaxins for alveolar macrophages

    Directory of Open Access Journals (Sweden)

    Donaldson Ken

    2005-12-01

    Full Text Available Abstract Background Alveolar macrophages are a key cell in dealing with particles deposited in the lungs and in determining the subsequent response to that particle exposure. Nanoparticles are considered a potential threat to the lungs and the mechanism of pulmonary response to nanoparticles is currently under intense scrutiny. The type II alveolar epithelial cell has previously been shown to release chemoattractants which can recruit alveolar macrophages to sites of particle deposition. The aim of this study was to assess the responses of a type II epithelial cell line (L-2 to both fine and nanoparticle exposure in terms of secretion of chemotactic substances capable of inducing macrophage migration. Results Exposure of type II cells to carbon black nanoparticles resulted in significant release of macrophage chemoattractant compared to the negative control and to other dusts tested (fine carbon black and TiO2 and nanoparticle TiO2 as measured by macrophage migration towards type II cell conditioned medium. SDS-PAGE analysis of the conditioned medium from particle treated type II cells revealed that a higher number of protein bands were present in the conditioned medium obtained from type II cells treated with nanoparticle carbon black compared to other dusts tested. Size-fractionation of the chemotaxin-rich supernatant determined that the chemoattractants released from the epithelial cells were between 5 and 30 kDa in size. Conclusion The highly toxic nature and reactive surface chemistry of the carbon black nanoparticles has very likely induced the type II cell line to release pro-inflammatory mediators that can potentially induce migration of macrophages. This could aid in the rapid recruitment of inflammatory cells to sites of particle deposition and the subsequent removal of the particles by phagocytic cells such as macrophages and neutrophils. Future studies in this area could focus on the exact identity of the substance(s released by the

  13. Scutellarin Suppresses NLRP3 Inflammasome Activation in Macrophages and Protects Mice against Bacterial Sepsis.

    Science.gov (United States)

    Liu, Yi; Jing, Yan-Yun; Zeng, Chen-Ying; Li, Chen-Guang; Xu, Li-Hui; Yan, Liang; Bai, Wen-Jing; Zha, Qing-Bing; Ouyang, Dong-Yun; He, Xian-Hui

    2017-01-01

    The NLRP3 inflammasome plays a critical role in mediating the innate immune defense against pathogenic infections, but aberrant activation of NLRP3 inflammasome has been linked to a variety of inflammatory diseases. Thus targeting the NLRP3 inflammasome represents a promising therapeutic for the treatment of such diseases. Scutellarin is a flavonoid isolated from Erigeron breviscapus (Vant.) Hand.-Mazz. and has been reported to exhibit potent anti-inflammatory activities, but the underlying mechanism is only partly understood. In this study, we aimed to investigate whether scutellarin could affect the activation of NLRP3 inflammasome in macrophages. The results showed that scutellarin dose-dependently reduced caspase-1 activation and decreased mature interleukin-1β (IL-1β) release in lipopolysaccharide (LPS)-primed macrophages upon ATP or nigericin stimulation, indicating that scutellarin inhibited NLRP3 inflammasome activation in macrophages. Consistent with this, scutellarin also suppressed pyroptotic cell death in LPS-primed macrophages treated with ATP or nigericin. ATP or nigericin-induced ASC speck formation and its oligomerization were blocked by scutellarin pre-treatment. Intriguingly, scutellarin augmented PKA-specific phosphorylation of NLRP3 in LPS-primed macrophages, which was completely blocked by selective PKA inhibitor H89, suggesting that PKA signaling had been involved in the action of scutellarin to suppress NLRP3 inflammasome activation. Supporting this, the inhibitory effect of scutellarin on NLRP3 inflammasome activation was completely counteracted by H89 or adenyl cyclase inhibitor MDL12330A. As NLRP3-dependent release of IL-1β has a critical role in sepsis, the in vivo activity of scutellarin was assayed in a mouse model of bacterial sepsis, which was established by intraperitoneally injection of a lethal dose of viable Escherichia coli . Oral administration of scutellarin significantly improved the survival of mice with bacterial sepsis

  14. Scutellarin Suppresses NLRP3 Inflammasome Activation in Macrophages and Protects Mice against Bacterial Sepsis

    Directory of Open Access Journals (Sweden)

    Yi Liu

    2018-01-01

    Full Text Available The NLRP3 inflammasome plays a critical role in mediating the innate immune defense against pathogenic infections, but aberrant activation of NLRP3 inflammasome has been linked to a variety of inflammatory diseases. Thus targeting the NLRP3 inflammasome represents a promising therapeutic for the treatment of such diseases. Scutellarin is a flavonoid isolated from Erigeron breviscapus (Vant. Hand.-Mazz. and has been reported to exhibit potent anti-inflammatory activities, but the underlying mechanism is only partly understood. In this study, we aimed to investigate whether scutellarin could affect the activation of NLRP3 inflammasome in macrophages. The results showed that scutellarin dose-dependently reduced caspase-1 activation and decreased mature interleukin-1β (IL-1β release in lipopolysaccharide (LPS-primed macrophages upon ATP or nigericin stimulation, indicating that scutellarin inhibited NLRP3 inflammasome activation in macrophages. Consistent with this, scutellarin also suppressed pyroptotic cell death in LPS-primed macrophages treated with ATP or nigericin. ATP or nigericin-induced ASC speck formation and its oligomerization were blocked by scutellarin pre-treatment. Intriguingly, scutellarin augmented PKA-specific phosphorylation of NLRP3 in LPS-primed macrophages, which was completely blocked by selective PKA inhibitor H89, suggesting that PKA signaling had been involved in the action of scutellarin to suppress NLRP3 inflammasome activation. Supporting this, the inhibitory effect of scutellarin on NLRP3 inflammasome activation was completely counteracted by H89 or adenyl cyclase inhibitor MDL12330A. As NLRP3-dependent release of IL-1β has a critical role in sepsis, the in vivo activity of scutellarin was assayed in a mouse model of bacterial sepsis, which was established by intraperitoneally injection of a lethal dose of viable Escherichia coli. Oral administration of scutellarin significantly improved the survival of mice with

  15. Macrophage activation by antiviral acyclic nucleoside phosphonates in dependence on priming immune stimuli

    Czech Academy of Sciences Publication Activity Database

    Zídek, Zdeněk; Franková, Daniela; Holý, Antonín

    2000-01-01

    Roč. 22, č. 12 (2000), s. 1121-1129 ISSN 0192-0561 R&D Projects: GA ČR GA305/00/0048; GA ČR GV203/96/K001 Institutional research plan: CEZ:AV0Z5008914 Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.142, year: 2000

  16. LIPOPOLYSACCHARIDE PRIMING AMPLIFIES LUNG MACROPHAGE TUMOR NECROSIS FACTOR PRODUCTION IN RESPONSE TO AIR PARTICLES. (R824790)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  17. Reprogramming of murine macrophages through TLR2 confers viral resistance via TRAF3-mediated, enhanced interferon production.

    Directory of Open Access Journals (Sweden)

    Darren J Perkins

    Full Text Available The cell surface/endosomal Toll-like Receptors (TLRs are instrumental in initiating immune responses to both bacteria and viruses. With the exception of TLR2, all TLRs and cytosolic RIG-I-like receptors (RLRs with known virus-derived ligands induce type I interferons (IFNs in macrophages or dendritic cells. Herein, we report that prior ligation of TLR2, an event previously shown to induce "homo" or "hetero" tolerance, strongly "primes" macrophages for increased Type I IFN production in response to subsequent TLR/RLR signaling. This occurs by increasing activation of the transcription factor, IFN Regulatory Factor-3 (IRF-3 that, in turn, leads to enhanced induction of IFN-β, while expression of other pro-inflammatory genes are suppressed (tolerized. In vitro or in vivo "priming" of murine macrophages with TLR2 ligands increase virus-mediated IFN induction and resistance to infection. This priming effect of TLR2 is mediated by the selective upregulation of the K63 ubiquitin ligase, TRAF3. Thus, we provide a mechanistic explanation for the observed antiviral actions of MyD88-dependent TLR2 and further define the role of TRAF3 in viral innate immunity.

  18. Cognate status and cross-script translation priming.

    Science.gov (United States)

    Voga, Madeleine; Grainger, Jonathan

    2007-07-01

    Greek-French bilinguals were tested in three masked priming experiments with Greek primes and French targets. Related primes were the translation equivalents of target words, morphologically related to targets, or phonologically related to targets. In Experiment 1, cognate translation equivalents (phonologically similar translations) showed facilitatory priming, relative to matched phonologically related primes, in conditions in which morphologically related primes showed no effect (50-msec prime exposure). Cross-language morphological priming emerged at longer prime exposure durations (66 msec), but cognate primes continued to generate more priming than did those in the morphological condition. In Experiments 2 and 3, the level of phonological overlap across translation equivalents was varied, and priming effects were measured against those for matched phonologically related primes and those in an unrelated prime condition. When measured against the unrelated baseline, cognate primes showed the typical advantage over noncognate primes. However, this cognate advantage disappeared when priming was measured against the phonologically related prime condition. The results are discussed in terms of how translation equivalents are represented in bilingual memory.

  19. The modulatory influence of the functional COMT Val158Met polymorphism on lexical decisions and semantic priming.

    Science.gov (United States)

    Reuter, Martin; Montag, Christian; Peters, Kristina; Kocher, Anne; Kiefer, Markus

    2009-01-01

    The role of the prefrontal Cortex (PFC) in higher cognitive functions - including working memory, conflict resolution, set shifting and semantic processing - has been demonstrated unequivocally. Despite the great heterogeneity among tasks measuring these phenotypes, due in part to the different cognitive sub-processes implied and the specificity of the stimulus material used, there is agreement that all of these tasks recruit an executive control system located in the PFC. On a biochemical level it is known that the dopaminergic system plays an important role in executive control functions. Evidence comes from molecular genetics relating the functional COMT Val158Met polymorphism to working memory and set shifting. In order determine whether this pattern of findings generalises to linguistic and semantic processing, we investigated the effects of the COMT Val158Met polymorphism in lexical decision making using masked and unmasked versions of the semantic priming paradigm on N = 104 healthy subjects. Although we observed strong priming effects in all conditions (masked priming, unmasked priming with short/long stimulus asynchronies (SOAs), direct and indirect priming), COMT was not significantly related to priming, suggesting no reliable influence on semantic processing. However, COMT Val158Met was strongly associated with lexical decision latencies in all priming conditions if considered separately, explaining between 9 and 14.5% of the variance. Therefore, the findings indicate that COMT mainly influences more general executive control functions in the PFC supporting the speed of lexical decisions.

  20. The modulatory influence of the functional COMT Val158Met polymorphism on lexical decisions and semantic priming

    Directory of Open Access Journals (Sweden)

    Martin Reuter

    2009-08-01

    Full Text Available The role of the prefrontal Cortex (PFC in higher cognitive functions - including working memory, conflict resolution, set shifting and semantic processing - has been demonstrated unequivocally. Despite the great heterogeneity among tasks measuring these phenotypes, due in part to the different cognitive sub-processes implied and the specificity of the stimulus material used, there is agreement that all of these tasks recruit an executive control system located in the PFC. On a biochemical level it is known that the dopaminergic system plays an important role in executive control functions. Evidence comes from molecular genetics relating the functional COMT Val158Met polymorphism to working memory and set shifting. In order determine whether this pattern of findings generalises to linguistic and semantic processing, we investigated the effects of the COMT Val158Met polymorphism in lexical decision making using masked and unmasked versions of the semantic priming paradigm on N=104 healthy subjects. Although we observed strong priming effects in all conditions (masked priming, unmasked priming with short/long stimulus asynchronies (SOAs, direct and indirect priming, COMT was not significantly related to masked priming, suggesting no reliable influence on semantic processing. However, COMT Val158Met was strongly associated with lexical decision latencies in all priming conditions if considered separately, explaining between 9 to 14.5 % of the variance. Therefore, the findings indicate that COMT mainly influences more general executive control functions in the PFC supporting the speed of lexical decisions.

  1. Self-Construal Priming Modulates Self-Evaluation under Social Threat

    Directory of Open Access Journals (Sweden)

    Tianyang Zhang

    2017-10-01

    Full Text Available Previous studies have shown that Westerners evaluate themselves in an especially flattering way when faced with a social-evaluative threat. The current study first investigated whether East Asians also have a similar pattern by recruiting Chinese participants and using social-evaluative threat manipulations in which participants perform self-evaluation tasks while adopting different social-evaluative feedbacks (Experiment 1. Then further examined whether the different response patterns can be modulated by different types of self-construal by using social-evaluative threat manipulations in conjunction with a self-construal priming task (Experiment 2. The results showed that, as opposed to Westerners' pattern, Chinese participants rated themselves as having significantly greater above-average effect only when faced with the nonthreatening feedback but not the social-evaluative threat. More importantly, we found that self-construal modulated the self-evaluation under social-evaluative threat: following independent self-construal priming, participants tended to show a greater above-average effect when faced with a social-evaluative threat. However, this pattern in conjunction with a social threat disappeared after participants received interdependent self-construal priming or neutral priming. These findings suggest that the effects of social-evaluative threat on self-evaluation are not culturally universal and is strongly modulated by self-construal priming.

  2. Signaling through MyD88 regulates leukocyte recruitment after brain injury

    DEFF Research Database (Denmark)

    Babcock, Alicia A; Toft-Hansen, Henrik; Owens, Trevor

    2008-01-01

    hippocampus. We now show that significant leukocyte entry into the EC occurs within 3-12 h of stab injury. Whereas T cells showed small, gradual increases over 8 days, macrophage infiltration was pronounced and peaked within 12-24 h. MyD88 deficiency significantly reduced macrophage and T cell recruitment...... for TNF-alpha, IL-1beta, and CCL2, which increased >50-fold after stab injury in C57BL/6 mice at the time of peak expression, were severely reduced in injured MyD88 knockout mice. Leukocyte recruitment and gene expression were unaffected in TLR2-deficient or TLR4 mutant mice. No significant differences...... in gene expression were observed in mice lacking IL-1R or IL-18R. These data show that MyD88-dependent signaling mediates proinflammatory gene expression and leukocyte recruitment after CNS injury....

  3. [Macrophage activation in atherosclerosis. Message 1: Activation of macrophages normally and in atherosclerotic lesions].

    Science.gov (United States)

    Nikiforov, N G; Kornienko, V Y; Karagodin, V P; Orekhov, A N

    2015-01-01

    Macrophages play important role in initiation and progression of inflammation in atherosclerosis. Plaque macrophages were shown to exhibit a phenotypic range that is intermediate between two extremes, M1 (proinflammatory) and M2 (anti-inflammatory). Indeed, in atherosclerosis, macrophages demonstrate phenotypic plasticity to rapidly adjust to changing microenvironmental conditions. In plaque macrophages demonstrate different phenotypes, and besides macrophage phenotypes could be changed. Phenotypes M1, M2, M4, Mhem, HA-mac, M(Hb) u Mox are described in the article. Ability of macrophages change their phenotype also considered.

  4. CX3CL1-mediated macrophage activation contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy.

    Science.gov (United States)

    Huang, Zhen-Zhen; Li, Dai; Liu, Cui-Cui; Cui, Yu; Zhu, He-Quan; Zhang, Wen-Wen; Li, Yong-Yong; Xin, Wen-Jun

    2014-08-01

    Painful peripheral neuropathy is a dose-limiting side effect of paclitaxel therapy, which hampers the optimal clinical management of chemotherapy in cancer patients. Currently the underlying mechanisms remain largely unknown. Here we showed that the clinically relevant dose of paclitaxel (3×8mg/kg, cumulative dose 24mg/kg) induced significant upregulation of the chemokine CX3CL1 in the A-fiber primary sensory neurons in vivo and in vitro and infiltration of macrophages into the dorsal root ganglion (DRG) in rats. Paclitaxel treatment also increased cleaved caspase-3 expression, induced the loss of primary afferent terminal fibers and decreased sciatic-evoked A-fiber responses in the spinal dorsal horn, indicating DRG neuronal apoptosis induced by paclitaxel. In addition, the paclitaxel-induced DRG neuronal apoptosis occurred exclusively in the presence of macrophage in vitro study. Intrathecal or systemic injection of CX3CL1 neutralizing antibody blocked paclitaxel-induced macrophage recruitment and neuronal apoptosis in the DRG, and also attenuated paclitaxel-induced allodynia. Furthermore, depletion of macrophage by systemic administration of clodronate inhibited paclitaxel-induced allodynia. Blocking CX3CL1 decreased activation of p38 MAPK in the macrophage, and inhibition of p38 MAPK activity blocked the neuronal apoptosis and development of mechanical allodynia induced by paclitaxel. These findings provide novel evidence that CX3CL1-recruited macrophage contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Recruiting in remote locations

    Energy Technology Data Exchange (ETDEWEB)

    Ionel, C. [Enerflex Systems Ltd., Calgary, AB (Canada)

    2006-07-01

    This presentation provided details of Enerflex, a leading supplier of products and services to the oil and gas industry, and outlined their personnel hiring policies. Enerflex's core values include community involvement and divisional logo branding. The extensive training that is provided places an emphasis on employee empowerment. The company also places an emphasis on employee safety, diversity, and team building. Competitive salaries are offered along with generous equipment allowances and a flexible benefits program. Benefits include travel and overtime rates; health benefits; retirement savings; scholarship programs; career opportunities; and apprenticeship programs. External technical training is provided. An employee referral program has been developed, and the company's recruitment program also advertises in remote newspapers to develop career streams within remote communities. tabs., figs.

  6. Boomerang recruitment: bridging the gap.

    Science.gov (United States)

    Hart, Karen A

    2009-01-01

    In today's competitive health care recruitment environment, one of the most cost-effective and successful recruitment strategies is alumni or "boomerang" recruitment. A proven business model, alumni recruitment is just beginning to be used in a significant way in the health care arena. The cost to recruit alumni is much lower than for those in the general workforce and the alumni population is a known quantity. Alumni will assimilate much more easily into your corporate culture, will need less orientation and onboarding, and will be more productive.

  7. The prime numbers and their distribution

    CERN Document Server

    Tenenbaum, Gerald

    2000-01-01

    One notable new direction this century in the study of primes has been the influx of ideas from probability. The goal of this book is to provide insights into the prime numbers and to describe how a sequence so tautly determined can incorporate such a striking amount of randomness. The book opens with some classic topics of number theory. It ends with a discussion of some of the outstanding conjectures in number theory. In between are an excellent chapter on the stochastic properties of primes and a walk through an elementary proof of the Prime Number Theorem. This book is suitable for anyone who has had a little number theory and some advanced calculus involving estimates. Its engaging style and invigorating point of view will make refreshing reading for advanced undergraduates through research mathematicians.

  8. Priming in Episodic and Semantic Memory.

    Science.gov (United States)

    McKoon, Gail; Ratcliff, Roger

    1979-01-01

    Four experiments examined priming between newly learned paired associates through two procedures, lexical decision and item recognition. Results argue against a functional separation of the semantic and episodic memory systems. (Author/AM)

  9. Bounded Gaps between Products of Special Primes

    Directory of Open Access Journals (Sweden)

    Ping Ngai Chung

    2014-03-01

    Full Text Available In their breakthrough paper in 2006, Goldston, Graham, Pintz and Yıldırım proved several results about bounded gaps between products of two distinct primes. Frank Thorne expanded on this result, proving bounded gaps in the set of square-free numbers with r prime factors for any r ≥ 2, all of which are in a given set of primes. His results yield applications to the divisibility of class numbers and the triviality of ranks of elliptic curves. In this paper, we relax the condition on the number of prime factors and prove an analogous result using a modified approach. We then revisit Thorne’s applications and give a better bound in each case.

  10. Preserved semantic priming effect in alexia.

    Science.gov (United States)

    Mimura, M; Goodglass, H; Milberg, W

    1996-09-01

    BH, a left-handed patient with alexia and nonfluent aphasia, was presented with a lexical-decision task in which words and pronounceable pseudowords were preceded by semantically related or unrelated picture primes (Experiment 1). In Experiment 2, BH was given an explicit reading task using the word lists from Experiment 1. Performance on Experiment 2 disclosed severe reading deficits in both oral reading and semantic matching of the words to pictures. However, in Experiment 1, BH demonstrated a significant semantic priming effect, responding more accurately and more quickly to words preceded by related primes than by unrelated primes. The present results suggest that even in a patient with severe alexia, implicit access to semantic information can be preserved in the absence of explicit identification. The possibility of categorical gradient in implicit activation (living vs. nonliving) in BH was also discussed, which, however, needs to be clarified in the further investigation.

  11. Suggestibility and negative priming: two replication studies.

    Science.gov (United States)

    David, Daniel; Brown, Richard J

    2002-07-01

    Research suggests that inhibiting the effect of irrelevant stimuli on subsequent thought and action (cognitive inhibition) may be an important component of suggestibility. Two small correlation studies were conducted to address the relationship between different aspects of suggestibility and individual differences in cognitive inhibition, operationalized as the degree of negative priming generated by to-be-ignored stimuli in a semantic categorization task. The first study found significant positive correlations between negative priming, hypnotic suggestibility, and creative imagination; a significant negative correlation was obtained between negative priming and interrogative suggestibility, demonstrating the discriminant validity of the study results. The second study replicated the correlation between negative priming and hypnotic suggestibility, using a different suggestibility measurement procedure that assessed subjective experience and hypnotic involuntariness as well as objective responses to suggestions. These studies support the notion that the ability to engage in cognitive inhibition may be an important component of hypnotic responsivity and maybe of other forms of suggestibility.

  12. Prime alternative algebras that are nearly commutative

    International Nuclear Information System (INIS)

    Pchelintsev, S V

    2004-01-01

    We prove that by deforming the multiplication in a prime commutative alternative algebra using a C-operation we obtain a prime non-commutative alternative algebra. Under certain restrictions on non-commutative algebras this relation between algebras is reversible. Isotopes are special cases of deformations. We introduce and study a linear space generated by the Bruck C-operations. We prove that the Bruck space is generated by operations of rank 1 and 2 and that 'general' Bruck operations of rank 2 are independent in the following sense: a sum of n operations of rank 2 cannot be written as a linear combination of (n-1) operations of rank 2 and an arbitrary operation of rank 1. We describe infinite series of non-isomorphic prime non-commutative algebras of bounded degree that are deformations of a concrete prime commutative algebra

  13. Semantic transparency affects morphological priming . . . eventually.

    Science.gov (United States)

    Heyer, Vera; Kornishova, Dana

    2018-05-01

    Semantic transparency has been in the focus of psycholinguistic research for decades, with the controversy about the time course of the application of morpho-semantic information during the processing of morphologically complex words not yet resolved. This study reports two masked priming studies with English - ness and Russian - ost' nominalisations, investigating how semantic transparency modulates native speakers' morphological priming effects at short and long stimulus onset asynchronies (SOAs). In both languages, we found increased morphological priming for nominalisations at the transparent end of the scale (e.g. paleness - pale) in comparison to items at the opaque end of the scale (e.g. business - busy) but only at longer prime durations. The present findings are in line with models that posit an initial phase of morpho-orthographic (semantically blind) decomposition.

  14. Syntactic Variance and Priming Effects in Translation

    DEFF Research Database (Denmark)

    Bangalore, Srinivas; Behrens, Bergljot; Carl, Michael

    2016-01-01

    The present work investigates the relationship between syntactic variation and priming in translation. It is based on the claim that languages share a common cognitive network of neural activity. When the source and target languages are solicited in a translation context, this shared network can...... lead to facilitation effects, so-called priming effects. We suggest that priming is a default setting in translation, a special case of language use where source and target languages are constantly co-activated. Such priming effects are not restricted to lexical elements, but do also occur...... on the syntactic level. We tested these hypotheses with translation data from the TPR database, more specifically for three language pairs (English-German, English-Danish, and English-Spanish). Our results show that response times are shorter when syntactic structures are shared. The model explains this through...

  15. Life history of plutonium dioxide in the lung: from macrophage to carcinoma

    International Nuclear Information System (INIS)

    Sanders, C.L.; Adee, R.R.; Rhoads, K.; Madison, R.M.

    1976-01-01

    The pulmonary macrophage exerts a large influence upon the distribution of alpha energy from inhaled 239 PuO 2 , while the pulmonary epithelium serves as the prime 'target' cell for neoplastic transformation. In the rat, of the total radiation energy absorbed in the lung, about 80 percent is delivered to the alveolar septae, 19 percent to the vascular tissues and less than 1 percent to the bronchial epithelium. Of the radiation energy delivered to the alveolar septae, about 10 percent is absorbed by alveolar epithelium, 10 percent by macrophage, 10 percent by endothelium and 70 percent by other cellular and noncellular elements. Both the type II alveolar epithelium and the bronchiolar epithelium serve as the probable cells of origin for induced adenocarcinoma

  16. Degree of handedness and priming: Further evidence for a distinction between production and identification priming mechanisms.

    Directory of Open Access Journals (Sweden)

    Donna J. LaVoie

    2015-02-01

    Full Text Available The distinction between implicit and explicit forms of memory retrieval is long-standing, and important to the extent it reveals how different neural architecture supports different aspects of memory function. Similarly, distinctions have been made between kinds of repetition priming, a form of implicit memory retrieval. This study focuses on the production-identification priming distinction, which delineates priming tasks involving verification of stimulus features as compared to priming tasks that require use of a cue to guide response retrieval. Studies investigating this dissociation in dementia or similar patient populations indicate that these forms of priming may differ in their neural bases. The current study looks at degree of handedness as a way of investigating inferred neural architecture supporting these two forms of priming. A growing body of research indicates that degree of handedness (consistent, or CH, versus inconsistent, or ICH is associated with greater interhemispheric interaction and functional access to right hemisphere processing in ICH, with superior performance seen in ICH on memory tasks reliant on this processing. Arguments about the theoretical mechanisms underlying identification and production forms of perceptual priming tasks suggest that performance on these tasks will differ as a function of degree of handedness. We tested this question in a group of CH and ICH young adults, who were asked to study lists of words prior to performing a production priming task (word stem completion, a perceptual word identification task, and a word stem cued recall task. While both handedness groups exhibited reliable priming across tasks, word stem completion priming was greater in ICH than CH participants, with identification priming not differing between groups. This dissociation supports the argument that production and identification forms of priming have different underlying neural bases.

  17. eHealth recruitment challenges.

    Science.gov (United States)

    Thompson, Debbe; Canada, Ashanti; Bhatt, Riddhi; Davis, Jennifer; Plesko, Lisa; Baranowski, Tom; Cullen, Karen; Zakeri, Issa

    2006-11-01

    Little is known about effective eHealth recruitment methods. This paper presents recruitment challenges associated with enrolling African-American girls aged 8-10 years in an eHealth obesity prevention program, their effect on the recruitment plan, and potential implications for eHealth research. Although the initial recruitment strategy was literature-informed, it failed to enroll the desired number of girls within a reasonable time period. Therefore, the recruitment strategy was reformulated to incorporate principles of social marketing and traditional marketing techniques. The resulting plan included both targeted, highly specific strategies (e.g., selected churches), and more broad-based approaches (e.g., media exposure, mass mailings, radio advertisements). The revised plan enabled recruitment goals to be attained. Media appeared to be particularly effective at reaching the intended audience. Future research should identify the most effective recruitment strategies for reaching potential eHealth audiences.

  18. Adoptive transfer of M2 macrophages reduces neuropathic pain via opioid peptides.

    Science.gov (United States)

    Pannell, Maria; Labuz, Dominika; Celik, Melih Ö; Keye, Jacqueline; Batra, Arvind; Siegmund, Britta; Machelska, Halina

    2016-10-07

    During the inflammation which occurs following nerve damage, macrophages are recruited to the site of injury. Phenotypic diversity is a hallmark of the macrophage lineage and includes pro-inflammatory M1 and anti-inflammatory M2 populations. Our aim in this study was to investigate the ability of polarized M0, M1, and M2 macrophages to secrete opioid peptides and to examine their relative contribution to the modulation of neuropathic pain. Mouse bone marrow-derived cells were cultured as unstimulated M0 macrophages or were stimulated into an M1 phenotype using lipopolysaccharide and interferon-γ or into an M2 phenotype using interleukin-4. The macrophage phenotypes were verified using flow cytometry for surface marker analysis and cytokine bead array for cytokine profile assessment. Opioid peptide levels were measured by radioimmunoassay and enzyme immunoassay. As a model of neuropathic pain, a chronic constriction injury (CCI) of the sciatic nerve was employed. Polarized M0, M1, and M2 macrophages (5 × 10 5 cells) were injected perineurally twice, on days 14 and 15 following CCI or sham surgery. Mechanical and heat sensitivity were measured using the von Frey and Hargreaves tests, respectively. To track the injected macrophages, we also transferred fluorescently stained polarized cells and analyzed the surface marker profile of endogenous and injected cells in the nerves ex vivo. Compared to M0 and M1 cells, M2 macrophages contained and released higher amounts of opioid peptides, including Met-enkephalin, dynorphin A (1-17), and β-endorphin. M2 cells transferred perineurally at the nerve injury site reduced mechanical, but not heat hypersensitivity following the second injection. The analgesic effect was reversed by the perineurally applied opioid receptor antagonist naloxone methiodide. M2 cells did not affect sensitivity following sham surgery. Neither M0 nor M1 cells altered mechanical and heat sensitivity in CCI or sham-operated animals. Tracing the

  19. Priming involuntary autobiographical memories in the lab

    OpenAIRE

    Barzykowski, Krystian; Niedźwieńska, Agnieszka

    2018-01-01

    Involuntary autobiographical memories (IAMs) are recollections of personal past that frequently and spontaneously occur in daily life. Initial studies by Mace. Priming involuntary autobiographical memories. Showed that deliberately reminiscing about a certain lifetime period (e.g., high school) significantly increased the number of different IAMs from the same period in subsequent days, suggesting that priming may play a significant role in the retrieval of IAMs in everyday life. In the prese...

  20. On the last digits of consecutive primes

    OpenAIRE

    Holt, Fred B.

    2016-01-01

    Recently Oliver and Soundararajan made conjectures based on computational enumerations about the frequency of occurrence of pairs of last digits for consecutive primes. By studying Eratosthenes sieve, we have identified discrete dynamic systems that exactly model the populations of gaps across stages of Eratosthenes sieve. Our models provide some insight into the observed biases in the occurrences of last digits in consecutive primes, and the models suggest that the biases will ultimately be ...

  1. Non-cognate translation priming in masked priming lexical decision experiments: A meta-analysis.

    Science.gov (United States)

    Wen, Yun; van Heuven, Walter J B

    2017-06-01

    The masked translation priming paradigm has been widely used in the last 25 years to investigate word processing in bilinguals. Motivated by studies reporting mixed findings, in particular for second language (L2) to first language (L1) translation priming, we conducted, for the first time in the literature, a meta-analysis of 64 masked priming lexical decision experiments across 24 studies to assess the effect sizes of L1-L2 and L2-L1 non-cognate translation priming effects in bilinguals. Our meta-analysis also investigated the influence of potential moderators of translation priming effects. The results provided clear evidence of significant translation priming effects for both directions, with L1-L2 translation priming significantly larger than L2-L1 translation priming (i.e., effect size of 0.86 vs. 0.31). The analyses also revealed that L1-L2 translation effect sizes were moderated by the interval between prime and target (ISI), whereas L2-L1 translation effect sizes were modulated by the number of items per cell. Theoretical and methodological implications of this meta-analysis are discussed and recommendations for future studies are provided.

  2. Doxycycline Attenuates Leptospira-Induced IL-1β by Suppressing NLRP3 Inflammasome Priming

    Directory of Open Access Journals (Sweden)

    Wenlong Zhang

    2017-07-01

    Full Text Available Doxycycline (Dox, a semisynthetic antibiotic, has been reported to exert multiple immunomodulatory effects. Treatment with Dox has a satisfactory curative effect against leptospirosis. In addition to its antibacterial action, we supposed that Dox also modulated immune response in controlling leptospira infection. Using J774A.1 mouse macrophages, the effects of Dox on protein and mRNA levels of IL-1β and TNF-α were investigated after infection with live or sonicated Leptospira interrogans serovar Lai strain Lai (56601. Specifically, the level of IL-1β but not TNF-α was sharply decreased when treated with Dox in leptospira-infected macrophages. Western blot analysis showed that Dox suppressed the activation of leptospira-induced MAPK and NF-κB signaling pathways. Using NLRP3-deficient and NLRC4-deficient mice, the data showed that the expression of leptospira-induced IL-1β was mainly dependent on the presence of NLRP3 inflammasome in macrophages. Meanwhile, Dox suppressed leptospira-induced NLRP3 inflammasome priming with the upregulation of the Na/K-ATPase Pump β1 subunit. The inhibition effect of Dox on IL-1β was also conspicuous in cells with lipopolysaccharide and ATP stimulation. These results were confirmed in vivo, as peritoneal fluids of mice and organs of hamsters expressed less IL-1β after treatment of leptospiral infection with Dox. Our results indicated that Dox also modulated immune response to attenuate leptospira-induced IL-1β by suppressing p38, JNK, p65, and NLRP3 inflammasome priming.

  3. Doxycycline Attenuates Leptospira-Induced IL-1β by Suppressing NLRP3 Inflammasome Priming

    Science.gov (United States)

    Zhang, Wenlong; Xie, Xufeng; Wu, Dianjun; Jin, Xuemin; Liu, Runxia; Hu, Xiaoyu; Fu, Yunhe; Ding, Zhuang; Zhang, Naisheng; Cao, Yongguo

    2017-01-01

    Doxycycline (Dox), a semisynthetic antibiotic, has been reported to exert multiple immunomodulatory effects. Treatment with Dox has a satisfactory curative effect against leptospirosis. In addition to its antibacterial action, we supposed that Dox also modulated immune response in controlling leptospira infection. Using J774A.1 mouse macrophages, the effects of Dox on protein and mRNA levels of IL-1β and TNF-α were investigated after infection with live or sonicated Leptospira interrogans serovar Lai strain Lai (56601). Specifically, the level of IL-1β but not TNF-α was sharply decreased when treated with Dox in leptospira-infected macrophages. Western blot analysis showed that Dox suppressed the activation of leptospira-induced MAPK and NF-κB signaling pathways. Using NLRP3-deficient and NLRC4-deficient mice, the data showed that the expression of leptospira-induced IL-1β was mainly dependent on the presence of NLRP3 inflammasome in macrophages. Meanwhile, Dox suppressed leptospira-induced NLRP3 inflammasome priming with the upregulation of the Na/K-ATPase Pump β1 subunit. The inhibition effect of Dox on IL-1β was also conspicuous in cells with lipopolysaccharide and ATP stimulation. These results were confirmed in vivo, as peritoneal fluids of mice and organs of hamsters expressed less IL-1β after treatment of leptospiral infection with Dox. Our results indicated that Dox also modulated immune response to attenuate leptospira-induced IL-1β by suppressing p38, JNK, p65, and NLRP3 inflammasome priming. PMID:28791016

  4. Prime implicants in dynamic reliability analysis

    International Nuclear Information System (INIS)

    Tyrväinen, Tero

    2016-01-01

    This paper develops an improved definition of a prime implicant for the needs of dynamic reliability analysis. Reliability analyses often aim to identify minimal cut sets or prime implicants, which are minimal conditions that cause an undesired top event, such as a system's failure. Dynamic reliability analysis methods take the time-dependent behaviour of a system into account. This means that the state of a component can change in the analysed time frame and prime implicants can include the failure of a component at different time points. There can also be dynamic constraints on a component's behaviour. For example, a component can be non-repairable in the given time frame. If a non-repairable component needs to be failed at a certain time point to cause the top event, we consider that the condition that it is failed at the latest possible time point is minimal, and the condition in which it fails earlier non-minimal. The traditional definition of a prime implicant does not account for this type of time-related minimality. In this paper, a new definition is introduced and illustrated using a dynamic flowgraph methodology model. - Highlights: • A new definition of a prime implicant is developed for dynamic reliability analysis. • The new definition takes time-related minimality into account. • The new definition is needed in dynamic flowgraph methodology. • Results can be represented by a smaller number of prime implicants.

  5. Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions.

    Science.gov (United States)

    Nishiwaki, Satoshi; Nakayama, Takayuki; Murata, Makoto; Nishida, Tetsuya; Terakura, Seitaro; Saito, Shigeki; Kato, Tomonori; Mizuno, Hiroki; Imahashi, Nobuhiko; Seto, Aika; Ozawa, Yukiyasu; Miyamura, Koichi; Ito, Masafumi; Takeshita, Kyosuke; Kato, Hidefumi; Toyokuni, Shinya; Nagao, Keisuke; Ueda, Ryuzo; Naoe, Tomoki

    2014-01-01

    Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that dexamethasone palmitate (DP), a liposteroid, can ameliorate such GVHD by inhibiting macrophage functions. We found that host-derived macrophages could exacerbate GVHD in a mouse model through expression of higher levels of pro-inflammatory TNF-α and IFN-γ, and lower levels of anti-inflammatory IL-10 than resident macrophages in mice without GVHD. DP significantly decreased the viability and migration capacity of primary mouse macrophages compared to conventional dexamethasone in vitro. DP treatment on day 7 and day 14 decreased macrophage number, and attenuated GVHD score and subsequent mortality in a murine model. This is the first study to provide evidence that therapy for GVHD should be changed on the basis of infiltrating cell type.

  6. DMPD: Macrophage differentiation and function in health and disease. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available in health and disease. PubmedID 18251777 Title Macrophage differentiation and function in health and disease...thol Int. 2008 Mar;58(3):143-55. (.png) (.svg) (.html) (.csml) Show Macrophage differentiation and function

  7. Semantic Priming for Coordinate Distant Concepts in Alzheimer's Disease Patients

    Science.gov (United States)

    Perri, R.; Zannino, G. D.; Caltagirone, C.; Carlesimo, G. A.

    2011-01-01

    Semantic priming paradigms have been used to investigate semantic knowledge in patients with Alzheimer's disease (AD). While priming effects produced by prime-target pairs with associative relatedness reflect processes at both lexical and semantic levels, priming effects produced by words that are semantically related but not associated should…

  8. Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice by induction of apoptosis of alveolar macrophages.

    Science.gov (United States)

    Ueno, Manabu; Maeno, Toshitaka; Nishimura, Satoshi; Ogata, Fusa; Masubuchi, Hiroaki; Hara, Kenichiro; Yamaguchi, Kouichi; Aoki, Fumiaki; Suga, Tatsuo; Nagai, Ryozo; Kurabayashi, Masahiko

    2015-03-10

    Alveolar macrophages play a crucial role in the pathogenesis of emphysema, for which there is currently no effective treatment. Bisphosphonates are widely used to treat osteoclast-mediated bone diseases. Here we show that delivery of the nitrogen-containing bisphosphonate alendronate via aerosol inhalation ameliorates elastase-induced emphysema in mice. Inhaled, but not orally ingested, alendronate inhibits airspace enlargement after elastase instillation, and induces apoptosis of macrophages in bronchoalveolar fluid via caspase-3- and mevalonate-dependent pathways. Cytometric analysis indicates that the F4/80(+)CD11b(high)CD11c(mild) population characterizing inflammatory macrophages, and the F4/80(+)CD11b(mild)CD11c(high) population defining resident alveolar macrophages take up substantial amounts of the bisphosphonate imaging agent OsteoSense680 after aerosol inhalation. We further show that alendronate inhibits macrophage migratory and phagocytotic activities and blunts the inflammatory response of alveolar macrophages by inhibiting nuclear factor-κB signalling. Given that the alendronate inhalation effectively induces apoptosis in both recruited and resident alveolar macrophages, we suggest this strategy may have therapeutic potential for the treatment of emphysema.

  9. IQGAP1 is involved in post-ischemic neovascularization by regulating angiogenesis and macrophage infiltration.

    Directory of Open Access Journals (Sweden)

    Norifumi Urao

    2010-10-01

    Full Text Available Neovascularization is an important repair mechanism in response to ischemic injury and is dependent on inflammation, angiogenesis and reactive oxygen species (ROS. IQGAP1, an actin-binding scaffold protein, is a key regulator for actin cytoskeleton and motility. We previously demonstrated that IQGAP1 mediates vascular endothelial growth factor (VEGF-induced ROS production and migration of cultured endothelial cells (ECs; however, its role in post-ischemic neovascularization is unknown.Ischemia was induced by left femoral artery ligation, which resulted in increased IQGAP1 expression in Mac3(+ macrophages and CD31(+ capillary-like ECs in ischemic legs. Mice lacking IQGAP1 exhibited a significant reduction in the post-ischemic neovascularization as evaluated by laser Doppler blood flow, capillary density and α-actin positive arterioles. Furthermore, IQGAP1(-/- mice showed a decrease in macrophage infiltration and ROS production in ischemic muscles, leading to impaired muscle regeneration and increased necrosis and fibrosis. The numbers of bone marrow (BM-derived cells in the peripheral blood were not affected in these knockout mice. BM transplantation revealed that IQGAP1 expressed in both BM-derived cells and tissue resident cells, such as ECs, is required for post-ischemic neovascularization. Moreover, thioglycollate-induced peritoneal macrophage recruitment and ROS production were inhibited in IQGAP1(-/- mice. In vitro, IQGAP1(-/- BM-derived macrophages showed inhibition of migration and adhesion capacity, which may explain the defective macrophage recruitment into the ischemic tissue in IQGAP1(-/- mice.IQGAP1 plays a key role in post-ischemic neovascularization by regulating, not only, ECs-mediated angiogenesis but also macrophage infiltration as well as ROS production. Thus, IQGAP1 is a potential therapeutic target for inflammation- and angiogenesis-dependent ischemic cardiovascular diseases.

  10. Mesenchymal stem cell-educated macrophages

    OpenAIRE

    Eggenhofer Elke; Hoogduijn Martin J

    2012-01-01

    Abstract Mesenchymal stem cells (MSC) mediate their immunosuppressive effects via a variety of mechanisms. One of these mechanisms involves the induction of macrophages with immunomodulatory capacities. This effect of MSC may be exploited when MSC are used as a cell therapeutic product. Furthermore, MSC are resident in tissues where they may locally target infiltrating macrophages to adapt more regulatory properties. The present review discusses the interaction between MSC and macrophages, th...

  11. Quantitative GPCR and ion channel transcriptomics in primary alveolar macrophages and macrophage surrogates

    Directory of Open Access Journals (Sweden)

    Groot-Kormelink Paul J

    2012-10-01

    Full Text Available Abstract Background Alveolar macrophages are one of the first lines of defence against invading pathogens and play a central role in modulating both the innate and acquired immune systems. By responding to endogenous stimuli within the lung, alveolar macrophages contribute towards the regulation of the local inflammatory microenvironment, the initiation of wound healing and the pathogenesis of viral and bacterial infections. Despite the availability of protocols for isolating primary alveolar macrophages from the lung these cells remain recalcitrant to expansion in-vitro and therefore surrogate cell types, such as monocyte derived macrophages and phorbol ester-differentiated cell lines (e.g. U937, THP-1, HL60 are frequently used to model macrophage function. Methods The availability of high throughput gene expression technologies for accurate quantification of transcript levels enables the re-evaluation of these surrogate cell types for use as cellular models of the alveolar macrophage. Utilising high-throughput TaqMan arrays and focussing on dynamically regulated families of integral membrane proteins, we explore the similarities and differences in G-protein coupled receptor (GPCR and ion channel expression in alveolar macrophages and their widely used surrogates. Results The complete non-sensory GPCR and ion channel transcriptome is described for primary alveolar macrophages and macrophage surrogates. The expression of numerous GPCRs and ion channels whose expression were hitherto not described in human alveolar macrophages are compared across primary macrophages and commonly used macrophage cell models. Several membrane proteins known to have critical roles in regulating macrophage function, including CXCR6, CCR8 and TRPV4, were found to be highly expressed in macrophages but not expressed in PMA-differentiated surrogates. Conclusions The data described in this report provides insight into the appropriate choice of cell models for

  12. In vitro Leishmania major promastigote-induced macrophage migration is modulated by sensory and autonomic neuropeptides

    DEFF Research Database (Denmark)

    Ahmed, A A; Wahbi, A; Nordlind, K

    1998-01-01

    Recruitment, migration and adherence of macrophages and their interaction with inoculated promastigotes are key steps in the initiation of the inflammatory process in cutaneous leishmaniasis. Parasite- and nervous system-derived factors might be involved in this process. In the present study...

  13. Motivated reasoning during recruitment.

    Science.gov (United States)

    Kappes, Heather Barry; Balcetis, Emily; De Cremer, David

    2018-03-01

    This research shows how job postings can lead job candidates to see themselves as particularly deserving of hiring and high salary. We propose that these entitlement beliefs entail both personal motivations to see oneself as deserving and the ability to justify those motivated judgments. Accordingly, we predict that people feel more deserving when qualifications for a job are vague and thus amenable to motivated reasoning, whereby people use information selectively to reach a desired conclusion. We tested this hypothesis with a 2-phase experiment (N = 892) using materials drawn from real online job postings. In the first phase of the experiment, participants believed themselves to be more deserving of hiring and deserving of higher pay after reading postings composed of vaguer types of qualifications. In the second phase, yoked observers believed that participants were less entitled overall, but did not selectively discount endorsement of vaguer qualifications, suggesting they were unaware of this effect. A follow-up preregistered experiment (N = 905) using postings with mixed qualification types replicated the effect of including more vague qualifications on participants' entitlement beliefs. Entitlement beliefs are widely seen as problematic for recruitment and retention, and these results suggest that reducing the inclusion of vague qualifications in job postings would dampen the emergence of these beliefs in applicants, albeit at the cost of decreasing application rates and lowering applicants' confidence. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  14. Macrophage antioxidant protection within atherosclerotic plaques.

    Science.gov (United States)

    Gieseg, Steven P; Leake, David S; Flavall, Elizabeth M; Amit, Zunika; Reid, Linzi; Yang, Ya-Ting

    2009-01-01

    Macrophage cells within inflammatory lesions are exposed to a wide range of degrading and cytotoxic molecules including reactive oxygen species. Unlike neutrophils, macrophages do not normally die in this environment but continue to generate oxidants, phagocytose cellular remains, and release a range of cyto-active agents which modulate the immune response. It is this potential of the macrophage cell to survive in an oxidative environment that allows the growth and complexity of advanced atherosclerotic plaques. This review will examine the oxidants encountered by macrophages within an atherosclerotic plaque and describe some of the potential antioxidant mechanisms which enable macrophages to function within inflammatory lesions. Ascorbate, a-tocopherol, and glutathione appear to be central to the protection of macrophages yet additional antioxidant mechanisms appear to be involved. Gamma-Interferon causes macrophages to generate 7,8-dihydroneopterin, neopterin and 3-hydroxyanthranilic acid both of which have antioxidant properties. Manganese superoxide dismutase is also upregulated in macrophages. The evidence that these antioxidants provide further protection, so allowing the macrophage cells to survive within sites of chronic inflammation such as atherosclerotic plaques, will be described.

  15. MONOCYTES AND MACROPHAGES IN PREGNANCY AND PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    Marijke M Faas

    2014-06-01

    Full Text Available Preeclampsia is an important complication in pregnancy, characterized byhypertension and proteinuria in the second half of pregnancy. Generalizedactivation of the inflammatory response is thought to play a role in thepathogenesis of preeclampsia. Monocytes may play a central role in thisinflammatory response. Monocytes are short lived cells, that mature in thecirculation and invade into tissues upon an inflammatory stimulus anddevelop into macrophages. Macrophages are abundantly present in theendometrium and play a role in implantation and placentation in normalpregnancy. In preeclampsia, these macrophages appear to be present in largernumbers and are also activated. In the present review we focused on the roleof monocytes and macrophages in the pathophysiology of preeclampsia.

  16. DMPD: Shaping of monocyte and macrophage function by adenosine receptors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17056121 Shaping of monocyte and macrophage function by adenosine receptors. Hasko ...tml) (.csml) Show Shaping of monocyte and macrophage function by adenosine receptors. PubmedID 17056121 Titl...e Shaping of monocyte and macrophage function by adenosine receptors. Authors Has

  17. DMPD: Macrophage activation by endogenous danger signals. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18161744 Macrophage activation by endogenous danger signals. Zhang X, Mosser DM. J ...Pathol. 2008 Jan;214(2):161-78. (.png) (.svg) (.html) (.csml) Show Macrophage activation by endogenous dange...r signals. PubmedID 18161744 Title Macrophage activation by endogenous danger signals. Authors Zhang X, Moss

  18. DMPD: Regulation of endogenous apolipoprotein E secretion by macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18388328 Regulation of endogenous apolipoprotein E secretion by macrophages. Kockx ...svg) (.html) (.csml) Show Regulation of endogenous apolipoprotein E secretion by macrophages. PubmedID 18388...328 Title Regulation of endogenous apolipoprotein E secretion by macrophages. Aut

  19. DMPD: Macrophage migration inhibitory factor and host innate immune responses tomicrobes. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14620137 Macrophage migration inhibitory factor and host innate immune responses to...microbes. Calandra T. Scand J Infect Dis. 2003;35(9):573-6. (.png) (.svg) (.html) (.csml) Show Macrophage migration... inhibitory factor and host innate immune responses tomicrobes. PubmedID 14620137 Title Macrophage migration

  20. DMPD: Cellular signaling in macrophage migration and chemotaxis. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11073096 Cellular signaling in macrophage migration and chemotaxis. Jones GE. J Leu...koc Biol. 2000 Nov;68(5):593-602. (.png) (.svg) (.html) (.csml) Show Cellular signaling in macrophage migration... and chemotaxis. PubmedID 11073096 Title Cellular signaling in macrophage migration and chemotaxis. Autho

  1. DMPD: Monocyte/macrophage traffic in HIV and SIV encephalitis. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12960230 Monocyte/macrophage traffic in HIV and SIV encephalitis. Kim WK, Corey S, ...Alvarez X, Williams K. J Leukoc Biol. 2003 Nov;74(5):650-6. Epub 2003 Aug 11. (.png) (.svg) (.html) (.csml) Show Monocyte/macrophage... traffic in HIV and SIV encephalitis. PubmedID 12960230 Title Monocyte/macrophage tr

  2. DMPD: CSF-1 and cell cycle control in macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 8981359 CSF-1 and cell cycle control in macrophages. Hamilton JA. Mol Reprod Dev. 1...997 Jan;46(1):19-23. (.png) (.svg) (.html) (.csml) Show CSF-1 and cell cycle control in macrophages. PubmedI...D 8981359 Title CSF-1 and cell cycle control in macrophages. Authors Hamilton JA. Publication Mol Reprod Dev

  3. DMPD: Silica binding and toxicity in alveolar macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18226603 Silica binding and toxicity in alveolar macrophages. Hamilton RF Jr, Thaku...l) Show Silica binding and toxicity in alveolar macrophages. PubmedID 18226603 Title Silica binding and toxicity in alveolar macropha...ges. Authors Hamilton RF Jr, Thakur SA, Holian A. Public

  4. DMPD: Iron regulation of hepatic macrophage TNFalpha expression. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11841920 Iron regulation of hepatic macrophage TNFalpha expression. Tsukamoto H. Fr...ee Radic Biol Med. 2002 Feb 15;32(4):309-13. (.png) (.svg) (.html) (.csml) Show Iron regulation of hepatic macrophage... TNFalpha expression. PubmedID 11841920 Title Iron regulation of hepatic macrophage TNFalpha expres

  5. Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy.

    Science.gov (United States)

    Zhao, Yang; Zhang, Chenran; Gao, Liquan; Yu, Xinhe; Lai, Jianhao; Lu, Dehua; Bao, Rui; Wang, Yanpu; Jia, Bing; Wang, Fan; Liu, Zhaofei

    2017-11-01

    Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission CT imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach. Cancer Res; 77(21); 6021-32. ©2017 AACR . ©2017 American Association for Cancer Research.

  6. Recruitment and selection of employees

    OpenAIRE

    Čermochová, Barbora

    2017-01-01

    The Bachelor's thesis focuses on the process of recruitment and selection of employees. The thesis is divided into theoretical and practical part. The theoretical part includes concepts that are important for understanding of issues of the process of recruitment and selection of employees. The practical part is divided into three chapters. The first chapter briefly describes the company xxx. Next two chapters deal with the process of recruitment and selection of employees in the company. The ...

  7. Rapid response learning of brand logo priming: Evidence that brand priming is not dominated by rapid response learning.

    Science.gov (United States)

    Boehm, Stephan G; Smith, Ciaran; Muench, Niklas; Noble, Kirsty; Atherton, Catherine

    2017-08-31

    Repetition priming increases the accuracy and speed of responses to repeatedly processed stimuli. Repetition priming can result from two complementary sources: rapid response learning and facilitation within perceptual and conceptual networks. In conceptual classification tasks, rapid response learning dominates priming of object recognition, but it does not dominate priming of person recognition. This suggests that the relative engagement of network facilitation and rapid response learning depends on the stimulus domain. Here, we addressed the importance of the stimulus domain for rapid response learning by investigating priming in another domain, brands. In three experiments, participants performed conceptual decisions for brand logos. Strong priming was present, but it was not dominated by rapid response learning. These findings add further support to the importance of the stimulus domain for the relative importance of network facilitation and rapid response learning, and they indicate that brand priming is more similar to person recognition priming than object recognition priming, perhaps because priming of both brands and persons requires individuation.

  8. Recruit and ADVANCE

    Science.gov (United States)

    Rosser, Sue V.

    2007-04-01

    Beginning in 2001, the National Science Foundation launched the ADVANCE Initiative, which has now awarded more than 70 million to some thirty institutions for transformations to advance women. Results of studies on how to attract and retain women students and faculty underpinned our ADVANCE Institutional Transformation grant funded by the NSF for 3.7 million for five years, beginning in 2001. As co-principal investigator on this grant, I insured that this research informed the five major threads of the grant: 1) Four termed ADVANCE professors to mentor junior women faculty in each college; 2) Collection of MIT-Report-like data indicators to assess whether advancement of women really occurs during and after the institutional transformation undertaken through ADVANCE; 3) Family-friendly policies and practices to stop the tenure clock and provide active service, modified duties, lactation stations and day care; 4) Mini-retreats to facilitate access for tenure-track women faculty to male decision-makers and administrators for informal conversations and discussion on topics important to women faculty; 5) Removal of subtle gender, racial, and other biases in promotion and tenure. The dynamic changes resulting from the grant in quality of mentoring, new understanding of promotion and tenure, numbers of women retained and given endowed chairs, and emergence of new family friendly policies gave me hope for genuine diversification of leadership in science and technology. As the grant funding ends, the absence of NSF prestige and monitoring, coupled with a change in academic leadership at the top, provide new challenges for institutionalization, recruitment, and advancement of women into leadership positions in science and engineering.

  9. Shifting evaluation windows : predictable forward primes with long SOAs eliminate the impact of backward primes.

    NARCIS (Netherlands)

    Fockenberg, D. A. F.; Koole, S.L.; Lakens, D.; Semin, G.R.

    2013-01-01

    Recent work suggests that people evaluate target stimuli within short and flexible time periods called evaluation windows. Stimuli that briefly precede a target (forward primes) or briefly succeed a target (backward primes) are often included in the target's evaluation. In this article, the authors

  10. Smelly primes – when olfactory primes do or do not work

    Directory of Open Access Journals (Sweden)

    Monique A Smeets

    2014-02-01

    Full Text Available In applied olfactory cognition the effects that olfactory stimulation can have on (human behavior are investigated. To enable an efficient application of olfactory stimuli a model of how they may lead to a change in behavior is proposed. To this end we use the concept of olfactory priming. Olfactory priming may prompt a special view on priming as the olfactory sense has some unique properties which make odors special types of primes. Examples of such properties are the ability of odors to influence our behavior outside of awareness, to lead to strong affective evaluations, to evoke specific memories, and to associate easily and quickly to other environmental stimuli. Opportunities and limitations for using odors as primes are related to these properties, and alternative explanations for reported findings are offered. Implications for olfactory semantic, construal, behavior and goal priming are given based on a brief overview of the priming literature from social psychology and from olfactory perception science. We end by formulating recommendations and ideas for a future research agenda and applications for olfactory priming.

  11. Scavenger receptor B1 facilitates macrophage uptake of silver nanoparticles and cellular activation

    Energy Technology Data Exchange (ETDEWEB)

    Aldossari, Abdullah A.; Shannahan, Jonathan H. [The University of Colorado Anschutz Medical Campus, Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences (United States); Podila, Ramakrishna [Clemson University, Department of Physics and Astronomy (United States); Brown, Jared M., E-mail: jared.brown@ucdenver.edu [The University of Colorado Anschutz Medical Campus, Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences (United States)

    2015-07-15

    Due to increased use of silver nanoparticles (AgNPs) for their antimicrobial activity, concerns have risen regarding potential adverse human health effects. Scavenger receptor B1 (SR-B1), a major receptor for high-density lipoprotein (HDL), is expressed by macrophages and has also been reported to play a role in recognition of negatively charged particles. We, therefore, hypothesized that SR-B1 mediates macrophage uptake of AgNPs and inflammatory activation. To test this hypothesis, we exposed a mouse macrophage cell line RAW264.7 (RAW) and bone marrow-derived macrophages (BMDM) to 20 nm citrate-suspended AgNPs. To verify the role of the SR-B1 receptor, we utilized a SR-B1 inhibitor (Blt2). In vitro studies demonstrated uptake of AgNPs and HDL-coated AgNPs by macrophages which were significantly reduced following pretreatment with Blt2. Inflammatory cytokine arrays revealed that macrophages exposed to AgNPs up-regulated expression of Tnf-α, Oncostatin m (OSM), Ccl4, Il17f, Ccl7, and Ccl2, whereas Il16 was found to be down-regulated. Macrophage activation was observed following AgNP and HDL-coated AgNP exposure as measured by OSM protein production and increased surface expression of CD86. These markers of activation were reduced with Blt2 pretreatment. The in vitro findings were confirmed in vivo through pulmonary instillation of AgNPs in mice. Pulmonary instillation of AgNPs resulted in a recruitment of inflammatory cells that were reduced in SR-B1-deficient mice or following Blt2 pretreatment. This study suggests that SR-B1 plays a major role in cellular recognition of AgNPs and the induction of cell responses that could contribute to inflammation caused by AgNP exposure.

  12. iNOS+ macrophages: potential alternate and tool for effective tumor therapy

    International Nuclear Information System (INIS)

    Prakash, Hridayesh; KIug, Felix; Jäger, Dirk; Hammerling, Gunter; Beckhove, Philipp

    2014-01-01

    Inefficient migration of immune effector cells in the tumor is a major limitation of effective therapy against solid tumors. This is due to immunosuppressive micro environment and impermissive endothelium which protects tumors from immune attack which is attributed to massive infiltration of tumors by macrophages which are known as tumor associated macrophages which are INOS low , Arginase- 1+ , Ym- 1+ , CD206 + (known as M2 or alternatively activated or tumor associated macrophages). Accumulation of M2 has been associated with the poor prognosis in the majority of cancer patients. Radiotherapy has recently been introduced as a potential strategy to improve cancer immunotherapy and tumor immune rejection. This is the only clinically advanced approach for noninvasive, site-specific intervention in cancer patients. Majority of cancer patients are routinely irradiated with therapeutic and high doses of γ-radiations which frequently manifest severe local/systemic acute. Low dose radiation (LDR) on the other hand may provide good alternatives of HDR for avoiding such toxicities. In this line, our pioneer study demonstrated that local/systemic low dose irradiation of tumors (2 Gy) effectively modified tumor micro environment and facilitated infiltration of peripheral immune effectors cells (T-cells) in neuroendocrine tumor of pancreas called insulinoma in RIP1-Tag5 (RT5) mice and primary human pancreatic carcinoma. Such tumor infiltration of T cells remained strictly dependent on iNOS + peritumoral macrophages. Our study also explicitly revealed that adoptive transfer of iNOS expressing macrophages in unirradiated RIP1-Tag5 (RT5) also offer a promising intervention to establish those populations of macrophages in the tumor tissue that enable therapeutic efficacy of cancer immunotherapy. We here demonstrate the critical role of iNOS + macrophages in joint regulation of tumor micro environment (angiogenesis) as well as effector T cell recruitment into tumor tissue and

  13. Scavenger receptor B1 facilitates macrophage uptake of silver nanoparticles and cellular activation

    Science.gov (United States)

    Aldossari, Abdullah A.; Shannahan, Jonathan H.; Podila, Ramakrishna; Brown, Jared M.

    2015-07-01

    Due to increased use of silver nanoparticles (AgNPs) for their antimicrobial activity, concerns have risen regarding potential adverse human health effects. Scavenger receptor B1 (SR-B1), a major receptor for high-density lipoprotein (HDL), is expressed by macrophages and has also been reported to play a role in recognition of negatively charged particles. We, therefore, hypothesized that SR-B1 mediates macrophage uptake of AgNPs and inflammatory activation. To test this hypothesis, we exposed a mouse macrophage cell line RAW264.7 (RAW) and bone marrow-derived macrophages (BMDM) to 20 nm citrate-suspended AgNPs. To verify the role of the SR-B1 receptor, we utilized a SR-B1 inhibitor (Blt2). In vitro studies demonstrated uptake of AgNPs and HDL-coated AgNPs by macrophages which were significantly reduced following pretreatment with Blt2. Inflammatory cytokine arrays revealed that macrophages exposed to AgNPs up-regulated expression of Tnf- α, Oncostatin m (OSM), Ccl4, Il17f, Ccl7, and Ccl2, whereas Il16 was found to be down-regulated. Macrophage activation was observed following AgNP and HDL-coated AgNP exposure as measured by OSM protein production and increased surface expression of CD86. These markers of activation were reduced with Blt2 pretreatment. The in vitro findings were confirmed in vivo through pulmonary instillation of AgNPs in mice. Pulmonary instillation of AgNPs resulted in a recruitment of inflammatory cells that were reduced in SR-B1-deficient mice or following Blt2 pretreatment. This study suggests that SR-B1 plays a major role in cellular recognition of AgNPs and the induction of cell responses that could contribute to inflammation caused by AgNP exposure.

  14. NOD2 enhances the innate response of alveolar macrophages to Mycobacterium tuberculosis in humans.

    Science.gov (United States)

    Juárez, Esmeralda; Carranza, Claudia; Hernández-Sánchez, Fernando; León-Contreras, Juan C; Hernández-Pando, Rogelio; Escobedo, Dante; Torres, Martha; Sada, Eduardo

    2012-04-01

    A role for the nucleotide-binding oligomerization domain 2 (NOD2) receptor in pulmonary innate immune responses has recently been explored. In the present study, we investigated the role that NOD2 plays in human alveolar macrophage innate responses and determined its involvement in the response to infection with virulent Mycobacterium tuberculosis. Our results showed that NOD2 was expressed in human alveolar macrophages, and significant amounts of IL-1β, IL-6, and TNF-α were produced upon ligand recognition with muramyldipeptide (MDP). NOD2 ligation induced the transcription and protein expression of the antimicrobial peptide LL37 and the autophagy enzyme IRGM in alveolar macrophages, demonstrating a novel function for this receptor in these cells. MDP treatment of alveolar macrophages improved the intracellular growth control of virulent M. tuberculosis; this was associated with a significant release of TNF-α and IL-6 and overexpression of bactericidal LL37. In addition, the autophagy proteins IRGM, LC3 and ATG16L1 were recruited to the bacteria-containing autophagosome after treatment with MDP. In conclusion, our results suggest that NOD2 can modulate the innate immune response of alveolar macrophages and play a role in the initial control of respiratory M. tuberculosis infections. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Telomerase Activation in Atherosclerosis and Induction of Telomerase Reverse Transcriptase Expression by Inflammatory Stimuli in Macrophages

    Science.gov (United States)

    Gizard, Florence; Heywood, Elizabeth B.; Findeisen, Hannes M.; Zhao, Yue; Jones, Karrie L.; Cudejko, Cèline; Post, Ginell R.; Staels, Bart; Bruemmer, Dennis

    2010-01-01

    Objective Telomerase serves as a critical regulator of tissue renewal. Although telomerase activity is inducible in response to various environmental cues, it remains unknown whether telomerase is activated during the inflammatory remodeling underlying atherosclerosis formation. To address this question, we investigated in the present study the regulation of telomerase in macrophages and during atherosclerosis development in LDL-receptor-deficient mice. Methods and Results We demonstrate that inflammatory stimuli activate telomerase in macrophages by inducing the expression of the catalytic subunit telomerase reverse transcriptase (TERT). Reporter and chromatin immunoprecipitation assays identified a previously unrecognized NF-κB response element in the TERT promoter, to which NF-κB is recruited during inflammation. Inhibition of NF-κB signaling completely abolished the induction of TERT expression, characterizing TERT as a bona fide NF-κB target gene. Furthermore, functional experiments revealed that TERT-deficiency results in a senescent cell phenotype. Finally, we demonstrate high levels of TERT expression in macrophages of human atherosclerotic lesions and establish that telomerase is activated during atherosclerosis development in LDL-receptor-deficient mice. Conclusion These results characterize TERT as a previously unrecognized NF-κB target gene in macrophages and demonstrate that telomerase is activated during atherosclerosis. This induction of TERT expression prevents macrophage senescence and may have important implications for the development of atherosclerosis. PMID:21106948

  16. Recruitment Practices And Institutional Change

    DEFF Research Database (Denmark)

    Holm, Anna; Ulhøi, John Parm

    Up to now, there has been little research on recruitment practices from an organizational perspective, and in part it lags behind practice. This paper attempts to rectify this by studying recent changes in the recruitment practices of Danish organizations. We employ new institutional theory......, and individuals’ social cognition. Among other things, this is reflected in the use of online recruitment and employer branding. The study concludes that the recruitment field has transformed and reviewed its practices due to institutional changes in how individuals search for employment and expect to be hired....

  17. Navy Enlisted Recruiting: Alternatives for Improving Recruiter Productivity

    Science.gov (United States)

    2013-03-01

    Instruction CR Chief Recruiter CRF Career Recruiting Force CS Culinary Specialist CT Command Trainer CTI Cryptologic Technician...third week (Module 2) when the students are taught about trends in sales and marketplaces, the art and science of sales, how to prospect for new...8, Aviation Machinist Mates (AD), Aviation Structural Mechanic (AM), Culinary Specialists (CS), and Fire Controlman (FC) had the highest average

  18. Nicotine Impairs Macrophage Control of Mycobacterium tuberculosis.

    Science.gov (United States)

    Bai, Xiyuan; Stitzel, Jerry A; Bai, An; Zambrano, Cristian A; Phillips, Matthew; Marrack, Philippa; Chan, Edward D

    2017-09-01

    Pure nicotine impairs macrophage killing of Mycobacterium tuberculosis (MTB), but it is not known whether the nicotine component in cigarette smoke (CS) plays a role. Moreover, the mechanisms by which nicotine impairs macrophage immunity against MTB have not been explored. To neutralize the effects of nicotine in CS extract, we used a competitive inhibitor to the nicotinic acetylcholine receptor (nAChR)-mecamylamine-as well as macrophages derived from mice with genetic disruption of specific subunits of nAChR. We also determined whether nicotine impaired macrophage autophagy and whether nicotine-exposed T regulatory cells (Tregs) could subvert macrophage anti-MTB immunity. Mecamylamine reduced the CS extract increase in MTB burden by 43%. CS extract increase in MTB was also significantly attenuated in macrophages from mice with genetic disruption of either the α7, β2, or β4 subunit of nAChR. Nicotine inhibited autophagosome formation in MTB-infected THP-1 cells and primary murine alveolar macrophages, as well as increased the intracellular MTB burden. Nicotine increased migration of THP-1 cells, consistent with the increased number of macrophages found in the lungs of smokers. Nicotine induced Tregs to produce transforming growth factor-β. Naive mouse macrophages co-cultured with nicotine-exposed Tregs had significantly greater numbers of viable MTB recovered with increased IL-10 production and urea production, but no difference in secreted nitric oxide as compared with macrophages cocultured with unexposed Tregs. We conclude that nicotine in CS plays an important role in subverting macrophage control of MTB infection.

  19. Anti-Inflammatory Effects of Lactobacillus Rahmnosus and Bifidobacterium Breve on Cigarette Smoke Activated Human Macrophages

    OpenAIRE

    Mortaz, E; Adcock, IM; Ricciardolo, FLM; Varahram, M; Jamaati, H; Velayati, AA; Folkerts, G; Garssen, J

    2015-01-01

    BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major global health problem with cigarette smoke (CS) as the main risk factor for its development. Airway inflammation in COPD involves the increased expression of inflammatory mediators such as CXCL-8 and IL-1β which are important mediators for neutrophil recruitment. Macrophages are an important source of these mediators in COPD. Lactobacillus rhamnosus (L. rhamnosus) and Befidobacterium breve (B. breve) attenuate the development...

  20. A Prime Example of the Maluma/Takete Effect? Testing for Sound Symbolic Priming.

    Science.gov (United States)

    Sidhu, David M; Pexman, Penny M

    2017-09-01

    Certain nonwords, like maluma and takete, are associated with roundness and sharpness, respectively. However, this has typically been demonstrated using explicit tasks. We investigated whether this association would be detectable using a more implicit measure-a sequential priming task. We began with a replication of the standard Maluma/Takete effect (Experiments 1a and 1b) before examining whether round and sharp nonword primes facilitated the categorization of congruent shapes (Experiment 2). We found modest evidence of a priming effect in response accuracy. We next examined whether nonword primes affected categorization of ambiguous shapes, using visual (Experiment 3) and auditory primes (Experiment 4). We found that ambiguous shapes were categorized as round (sharp) more often following the presentation of a round (sharp) nonword. This suggests that phonemes may activate related shape information which then affects the processing of shapes, and that this association emerges even when participants are not explicitly searching for it. Copyright © 2016 Cognitive Science Society, Inc.

  1. Repetition Priming Magnitude Depends on Affirmative Prime Responses: A Test of Two Congruity Explanations.

    Science.gov (United States)

    Fiet, Paula; Sorensen, Linda; Mayne, Zachary; Corgiat, Damon; Woltz, Dan

    2016-01-01

    We conducted 2 experiments to evaluate the impact of positive prime responses on repetition priming effects while decoupling this impact from content congruity and specific evaluation operations. Our first experiment consisted of word-meaning comparison trials that required participants to evaluate synonyms or antonyms. A crossing of evaluation operation with semantic content allowed us to test the goal-content congruity hypothesis against the semantic congruity explanation for greater facilitation from positive response primes. Results suggested that operation-based priming is affected by goal-content congruity. A second experiment tested the observed effect of positive responses on repetition priming using mental rotation of irregular shapes, affording a test of the impact of congruity in evaluation goals and content in a nonverbal stimulus domain. Both experiments produced a pattern of results inconsistent with Schulman's (1974) semantic congruity account and instead implicated a different form of congruity that affects memory for prior operations rather than memory for semantic and episodic content.

  2. CYLD Proteolysis Protects Macrophages from TNF-Mediated Auto-necroptosis Induced by LPS and Licensed by Type I IFN

    Directory of Open Access Journals (Sweden)

    Diana Legarda

    2016-06-01

    Full Text Available Tumor necrosis factor (TNF induces necroptosis, a RIPK3/MLKL-dependent form of inflammatory cell death. In response to infection by Gram-negative bacteria, multiple receptors on macrophages, including TLR4, TNF, and type I IFN receptors, are concurrently activated, but it is unclear how they crosstalk to regulate necroptosis. We report that TLR4 activates CASPASE-8 to cleave and remove the deubiquitinase cylindromatosis (CYLD in a TRIF- and RIPK1-dependent manner to disable necroptosis in macrophages. Inhibiting CASPASE-8 leads to CYLD-dependent necroptosis caused by the TNF produced in response to TLR4 ligation. While lipopolysaccharides (LPS-induced necroptosis was abrogated in Tnf−/− macrophages, a soluble TNF antagonist was not able to do so in Tnf+/+ macrophages, indicating that necroptosis occurs in a cell-autonomous manner. Surprisingly, TNF-mediated auto-necroptosis of macrophages requires type I IFN, which primes the expression of key necroptosis-signaling molecules, including TNFR2 and MLKL. Thus, the TNF necroptosis pathway is regulated by both negative and positive crosstalk.

  3. Priming intelligent behavior: an elusive phenomenon.

    Directory of Open Access Journals (Sweden)

    David R Shanks

    Full Text Available Can behavior be unconsciously primed via the activation of attitudes, stereotypes, or other concepts? A number of studies have suggested that such priming effects can occur, and a prominent illustration is the claim that individuals' accuracy in answering general knowledge questions can be influenced by activating intelligence-related concepts such as professor or soccer hooligan. In 9 experiments with 475 participants we employed the procedures used in these studies, as well as a number of variants of those procedures, in an attempt to obtain this intelligence priming effect. None of the experiments obtained the effect, although financial incentives did boost performance. A Bayesian analysis reveals considerable evidential support for the null hypothesis. The results conform to the pattern typically obtained in word priming experiments in which priming is very narrow in its generalization and unconscious (subliminal influences, if they occur at all, are extremely short-lived. We encourage others to explore the circumstances in which this phenomenon might be obtained.

  4. A computational approach to negative priming

    Science.gov (United States)

    Schrobsdorff, H.; Ihrke, M.; Kabisch, B.; Behrendt, J.; Hasselhorn, M.; Herrmann, J. Michael

    2007-09-01

    Priming is characterized by a sensitivity of reaction times to the sequence of stimuli in psychophysical experiments. The reduction of the reaction time observed in positive priming is well-known and experimentally understood (Scarborough et al., J. Exp. Psycholol: Hum. Percept. Perform., 3, pp. 1-17, 1977). Negative priming—the opposite effect—is experimentally less tangible (Fox, Psychonom. Bull. Rev., 2, pp. 145-173, 1995). The dependence on subtle parameter changes (such as response-stimulus interval) usually varies. The sensitivity of the negative priming effect bears great potential for applications in research in fields such as memory, selective attention, and ageing effects. We develop and analyse a computational realization, CISAM, of a recent psychological model for action decision making, the ISAM (Kabisch, PhD thesis, Friedrich-Schiller-Universitat, 2003), which is sensitive to priming conditions. With the dynamical systems approach of the CISAM, we show that a single adaptive threshold mechanism is sufficient to explain both positive and negative priming effects. This is achieved by comparing results obtained by the computational modelling with experimental data from our laboratory. The implementation provides a rich base from which testable predictions can be derived, e.g. with respect to hitherto untested stimulus combinations (e.g. single-object trials).

  5. Affective Priming in Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Joelle eLeMoult

    2012-10-01

    Full Text Available Research on cognitive biases in depression has provided considerable evidence for the impact of emotion on cognition. Individuals with depression tend to preferentially process mood-congruent material and to show deficits in the processing of positive material leading to biases in attention, memory, and judgments. More research is needed, however, to fully understand which cognitive processes are affected. The current study further examines the impact of emotion on cognition using a priming design with facial expressions of emotion. Specifically, this study tested whether the presentation of facial expressions of emotion affects subsequent processing of affective material in participants with major depressive disorder (MDD and healthy controls (CTL. Facial expressions displaying happy, sad, angry, disgusted, or neutral expressions were presented as primes for 500ms, and participants’ speed to identify a subsequent target’s emotional expression was assessed. All participants displayed greater interference from emotional versus neutral primes, marked by slower response times to judge the emotion of the target face when it was preceded by an emotional prime. Importantly, the CTL group showed the strongest interference when happy emotional expressions served as primes whereas the MDD group failed to show this bias. These results add to a growing literature that shows that depression is associated with difficulties in the processing of positive material.

  6. Priming Intelligent Behavior: An Elusive Phenomenon

    Science.gov (United States)

    Shanks, David R.; Newell, Ben R.; Lee, Eun Hee; Balakrishnan, Divya; Ekelund, Lisa; Cenac, Zarus; Kavvadia, Fragkiski; Moore, Christopher

    2013-01-01

    Can behavior be unconsciously primed via the activation of attitudes, stereotypes, or other concepts? A number of studies have suggested that such priming effects can occur, and a prominent illustration is the claim that individuals' accuracy in answering general knowledge questions can be influenced by activating intelligence-related concepts such as professor or soccer hooligan. In 9 experiments with 475 participants we employed the procedures used in these studies, as well as a number of variants of those procedures, in an attempt to obtain this intelligence priming effect. None of the experiments obtained the effect, although financial incentives did boost performance. A Bayesian analysis reveals considerable evidential support for the null hypothesis. The results conform to the pattern typically obtained in word priming experiments in which priming is very narrow in its generalization and unconscious (subliminal) influences, if they occur at all, are extremely short-lived. We encourage others to explore the circumstances in which this phenomenon might be obtained. PMID:23637732

  7. Proprotein convertase 1/3 inhibited macrophages: A novel therapeutic based on drone macrophages.

    Science.gov (United States)

    Duhamel, Marie; Rodet, Franck; Murgoci, Adriana; Wisztorski, Maxence; Day, Robert; Fournier, Isabelle; Salzet, Michel

    2016-06-01

    We demonstrated here thanks to proteomic, that proprotein convertase 1/3 knockdown macrophages present all the characteristic of activated pro-inflammatory macrophages. TLR4 and TLR9 signaling pathways can be enhanced leading to the secretion of pro-inflammatory factors and antitumor factors. We can control their activation by controlling one enzyme, PC1/3. In a tumor context, PC1/3 inhibition in macrophages may reactivate them and lead to a cytokine storm after stimulation "at distance" with a TLR ligand. Therefore, we name these proprotein convertase inhibited macrophages the "drone macrophages". They constitute an innovative cell therapy to treat efficiently tumors.

  8. Leading, but not trailing, primes influence temporal order perception: further evidence for an attentional account of perceptual latency priming.

    Science.gov (United States)

    Scharlau, Ingrid

    2002-11-01

    Presenting a masked prime leading a target influences the perceived onset of the masking target (perceptual latency priming; Scharlau & Neumann, in press). This priming effect is explained by the asynchronous updating model (Neumann, 1982; Scharlau & Neumann, in press): The prime initiates attentional allocation toward its location, which renders a trailing target at the same place consciously available earlier. In three experiments, this perceptual latency priming by leading primes was examined jointly with the effects of trailing primes in order to compare the explanation of the asynchronous updating model with the onset-averaging and the P-center hypotheses. Experiment 1 showed that an attended, as well as an unattended, prime leads to perceptual latency priming. In addition, a large effect of trailing primes on the onset of a target was found. As Experiment 2 demonstrated, this effect is quite robust, although smaller than that of a leading prime. In Experiment 3, masked primes were used. Under these conditions, no influence of trailing primes could be found, whereas perceptual latency priming persisted. Thus, a nonattentional explanation for the effect of trailing primes seems likely.

  9. Ameloginins promote an alternatively activated macrophage phenotype in vitro

    DEFF Research Database (Denmark)

    Almqvist, S; Werthen, M; Lyngstadas, SP

    2011-01-01

    aggregates were visualised by transmission electron microscopy. The amelogenin treatment of macrophages increased several pro- and anti-inflammatory cytokines, including alternative macrophage activation marker AMAC-1 (p

  10. Macrophage diversity in renal injury and repair

    NARCIS (Netherlands)

    Ricardo, Sharon D.; van Goor, Harry; Eddy, Allison A.

    Monocyte-derived macrophages can determine the outcome of the immune response and whether this response contributes to tissue repair or mediates tissue destruction. In addition to their important role in immune-mediated renal disease and host defense, macrophages play a fundamental role in tissue

  11. Macrophage polarization: the epigenetic point of view

    NARCIS (Netherlands)

    van den Bossche, Jan; Neele, Annette E.; Hoeksema, Marten A.; de Winther, Menno P. J.

    2014-01-01

    The first functions of macrophages to be identified by Metchnikoff were phagocytosis and microbial killing. Although these are important features, macrophages are functionally very complex and involved in virtually all aspects of life, from immunity and host defense, to homeostasis, tissue repair

  12. Macrophages Promote Axon Regeneration with Concurrent Neurotoxicity

    NARCIS (Netherlands)

    Gensel, J.C.; Nakamura, S.; Guan, Z.; Rooijen, van N.; Ankeny, D.P.; Popovich, P.G.

    2009-01-01

    Activated macrophages can promote regeneration of CNS axons. However, macrophages also release factors that kill neurons. These opposing functions are likely induced simultaneously but are rarely considered together in the same experimental preparation. A goal of this study was to unequivocally

  13. Genesis and kinetics of peritoneal macrophages

    International Nuclear Information System (INIS)

    Wacker, H.H.

    1982-01-01

    The author intended to develop an experimental model for investigations of the proliferation kinetics of tissue macrophages, using the example of peritoneal macrophages. To get a suitable cell population, a blood cell population was labelled with 3 H-thymidine and transferred in a parabiotic test. (orig./MG) [de

  14. Macrophage Activation Mechanisms in Human Monocytic Cell Line-derived Macrophages.

    Science.gov (United States)

    Sumiya, Yu; Ishikawa, Mami; Inoue, Takahiro; Inui, Toshio; Kuchiike, Daisuke; Kubo, Kentaro; Uto, Yoshihiro; Nishikata, Takahito

    2015-08-01

    Although the mechanisms of macrophage activation are important for cancer immunotherapy, they are poorly understood. Recently, easy and robust assay systems for assessing the macrophage-activating factor (MAF) using monocytic cell line-derived macrophages were established. Gene-expression profiles of U937- and THP-1-derived macrophages were compared using gene expression microarray analysis and their responses against several MAFs were examined by in vitro experiments. Activated states of these macrophages could not be assigned to a specific sub-type but showed, however, different unique characteristics. The unique of monocytic cell line-derived macrophages could provide clues to understand the activation mechanism of macrophages and, therefore, help to develop effective cancer immunotherapy with MAFs. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  15. Purinergic signaling during macrophage differentiation results in M2 alternative activated macrophages.

    Science.gov (United States)

    Barberà-Cremades, Maria; Baroja-Mazo, Alberto; Pelegrín, Pablo

    2016-02-01

    Macrophages represent a highly heterogenic cell population of the innate immune system, with important roles in the initiation and resolution of the inflammatory response. Purinergic signaling regulates both M1 and M2 macrophage function at different levels by controlling the secretion of cytokines, phagocytosis, and the production of reactive oxygen species. We found that extracellular nucleotides arrest macrophage differentiation from bone marrow precursors via adenosine and P2 receptors. This results in a mature macrophage with increased expression of M2, but not M1, genes. Similar to adenosine and ATP, macrophage growth arrested with LPS treatment resulted in an increase of the M2-related marker Ym1. Recombinant Ym1 was able to affect macrophage proliferation and could, potentially, be involved in the arrest of macrophage growth during hematopoiesis. © Society for Leukocyte Biology.

  16. Alternatively activated macrophages (M2 macrophages) in the skin of patient with localized scleroderma.

    Science.gov (United States)

    Higashi-Kuwata, Nobuyo; Makino, Takamitsu; Inoue, Yuji; Takeya, Motohiro; Ihn, Hironobu

    2009-08-01

    Localized scleroderma is a connective tissue disorder that is limited to the skin and subcutaneous tissue. Macrophages have been reported to be particularly activated in patients with skin disease including systemic sclerosis and are potentially important sources for fibrosis-inducing cytokines, such as transforming growth factor beta. To clarify the features of immunohistochemical characterization of the immune cell infiltrates in localized scleroderma focusing on macrophages, skin biopsy specimens were analysed by immunohistochemistry. The number of cells stained with monoclonal antibodies, CD68, CD163 and CD204, was calculated. An evident macrophage infiltrate and increased number of alternatively activated macrophages (M2 macrophages) in their fibrotic areas were observed along with their severity of inflammation. This study revealed that alternatively activated macrophages (M2 macrophages) may be a potential source of fibrosis-inducing cytokines in localized scleroderma, and may play a crucial role in the pathogenesis of localized scleroderma.

  17. Mycobacteria, Metals, and the Macrophage

    Science.gov (United States)

    Niederweis, Michael; Wolschendorf, Frank; Mitra, Avishek; Neyrolles, Olivier

    2015-01-01

    Summary Mycobacterium tuberculosis is a facultative intracellular pathogen that thrives inside host macrophages. A key trait of M. tuberculosis is to exploit and manipulate metal cation trafficking inside infected macrophages to ensure survival and replication inside the phagosome. Here we describe the recent fascinating discoveries that the mammalian immune system responds to infections with M. tuberculosis by overloading the phagosome with copper and zinc, two metals which are essential nutrients in small quantities but are toxic in excess. M. tuberculosis has developed multi-faceted resistance mechanisms to protect itself from metal toxicity including control of uptake, sequestration inside the cell, oxidation, and efflux. The host response to infections combines this metal poisoning strategy with nutritional immunity mechanisms that deprive M. tuberculosis from metals such as iron and manganese to prevent bacterial replication. Both immune mechanisms rely on the translocation of metal transporter proteins to the phagosomal membrane during the maturation process of the phagosome. This review summarizes these recent findings and discusses how metal-targeted approaches might complement existing TB chemotherapeutic regimens with novel anti-infective therapies. PMID:25703564

  18. Positions priming in briefly presented search arrays

    DEFF Research Database (Denmark)

    Asgeirsson, Arni Gunnar; Kristjánsson, Árni; Kyllingsbæk, Søren

    2011-01-01

    Repetition priming in visual search has been a topic of extensive research since Maljkovic & Nakayama [1994, Memory & Cognition, 22, 657-672] presented the first detailed studies of such effects. Their results showed large reductions in reaction times when target color was repeated on consecutive...... the targets are oddly colored alphanumeric characters. The effects arise at very low exposure durations and benefit accuracy at all exposure durations towards the subjects’ ceiling. We conclude that temporally constricted experimental conditions can add to our understanding priming in visual search...... pop-out search trials. Such repetition effects have since been generalized to a multitude of target attributes. Priming has primarily been investigated using self-terminating visual search paradigms, comparing differences in response times. Response accuracy has predominantly served as a control...

  19. Prime Minister of Pakistan visits CERN

    CERN Multimedia

    Anaïs Schaeffer

    2016-01-01

    On Saturday, 23 January 2016, CERN welcomed Mr Muhammad Nawaz Sharif, Prime Minister of Pakistan.   From left to right: Minister of Finance Mr Mohammad Ishaq Dar, Prime Minister of the Islamic Republic of Pakistan, Muhammad Nawaz Sharif, CERN Director-General Fabiola Gianotti and CMS national contact physicist Hafeez Hoorani. Mr Muhammad Nawaz Sharif arrived at Point 5 in Cessy, where he was welcomed onto French soil by the sous-préfet of Cessy, Stéphane Donnot, and, representing CERN, Director-General Fabiola Gianotti, Directors Eckhard Elsen and Charlotte Warakaulle, and Rüdiger Voss, the adviser for relations with Pakistan. It was the first visit by a head of government of Pakistan since the country became CERN's latest Associate Member State in July 2015. The Prime Minister then had the opportunity to visit the CMS underground experimental area accompanied by the CMS Spokesperson, Tiziano Camporesi, and the CMS collaboration’...

  20. Affective priming using facial expressions modulates liking for abstract art.

    Science.gov (United States)

    Flexas, Albert; Rosselló, Jaume; Christensen, Julia F; Nadal, Marcos; Olivera La Rosa, Antonio; Munar, Enric

    2013-01-01

    We examined the influence of affective priming on the appreciation of abstract artworks using an evaluative priming task. Facial primes (showing happiness, disgust or no emotion) were presented under brief (Stimulus Onset Asynchrony, SOA = 20 ms) and extended (SOA = 300 ms) conditions. Differences in aesthetic liking for abstract paintings depending on the emotion expressed in the preceding primes provided a measure of the priming effect. The results showed that, for the extended SOA, artworks were liked more when preceded by happiness primes and less when preceded by disgust primes. Facial expressions of happiness, though not of disgust, exerted similar effects in the brief SOA condition. Subjective measures and a forced-choice task revealed no evidence of prime awareness in the suboptimal condition. Our results are congruent with findings showing that the affective transfer elicited by priming biases evaluative judgments, extending previous research to the domain of aesthetic appreciation.

  1. Affective priming using facial expressions modulates liking for abstract art.

    Directory of Open Access Journals (Sweden)

    Albert Flexas

    Full Text Available We examined the influence of affective priming on the appreciation of abstract artworks using an evaluative priming task. Facial primes (showing happiness, disgust or no emotion were presented under brief (Stimulus Onset Asynchrony, SOA = 20 ms and extended (SOA = 300 ms conditions. Differences in aesthetic liking for abstract paintings depending on the emotion expressed in the preceding primes provided a measure of the priming effect. The results showed that, for the extended SOA, artworks were liked more when preceded by happiness primes and less when preceded by disgust primes. Facial expressions of happiness, though not of disgust, exerted similar effects in the brief SOA condition. Subjective measures and a forced-choice task revealed no evidence of prime awareness in the suboptimal condition. Our results are congruent with findings showing that the affective transfer elicited by priming biases evaluative judgments, extending previous research to the domain of aesthetic appreciation.

  2. Diversity employment and recruitment sources

    Energy Technology Data Exchange (ETDEWEB)

    1994-08-01

    Effective human resources management has been identified as one of four critical success factors in the Department of Energy Strategic Plan. The Plan states relative to this factor: ``The Department seeks greater alignment of resources with agency priorities and increased diversification of the workforce, including gender, ethnicity, age, and skills. This diversification will bring new thinking and perspectives that heretofore have not had a voice in departmental decision-making.`` This Guide has been developed as a key tool to assist Department of Energy management and administrative staff in achieving Goal 2 of this critical success factor, which is to ``Ensure a diverse and talented workforce.`` There are numerous sources from which to recruit minorities, women and persons with disabilities. Applying creativity and proactive effort, using traditional and non-traditional approaches, and reaching out to various professional, academic and social communities will increase the reservoir of qualified candidates from which to make selections. In addition, outreach initiatives will undoubtedly yield further benefits such as a richer cultural understanding and diversity awareness. The resource listings presented in this Guide are offered to encourage active participation in the diversity recruitment process. This Guide contains resource listings by state for organizations in the following categories: (1) African American Recruitment Sources; (2) Asian American/Pacific Islander Recruitment Sources; (3) Hispanic Recruitment Sources; (4) Native American/Alaskan Native Recruitment Sources; (5) Persons with Disabilities Recruitment Sources; and (6) Women Recruitment Sources.

  3. Fast-Track Teacher Recruitment.

    Science.gov (United States)

    Grant, Franklin Dean

    2001-01-01

    Schools need a Renaissance human-resources director to implement strategic staffing and fast-track teacher-recruitment plans. The HR director must attend to customer satisfaction, candidate supply, web-based recruitment possibilities, stabilization of newly hired staff, retention of veteran staff, utilization of retired employees, and latest…

  4. Unraveling Macrophage Heterogeneity in Erythroblastic Islands

    Directory of Open Access Journals (Sweden)

    Katie Giger Seu

    2017-09-01

    Full Text Available Mammalian erythropoiesis occurs within erythroblastic islands (EBIs, niches where maturing erythroblasts interact closely with a central macrophage. While it is generally accepted that EBI macrophages play an important role in erythropoiesis, thorough investigation of the mechanisms by which they support erythropoiesis is limited largely by inability to identify and isolate the specific macrophage sub-population that constitute the EBI. Early studies utilized immunohistochemistry or immunofluorescence to study EBI morphology and structure, while more recent efforts have used flow cytometry for high-throughput quantitative characterization of EBIs and their central macrophages. However, these approaches based on the expectation that EBI macrophages are a homogeneous population (F4/80+/CD169+/VCAM-1+ for example provide an incomplete picture and potentially overlook critical information about the nature and biology of the islands and their central macrophages. Here, we present a novel method for analysis of EBI macrophages from hematopoietic tissues of mice and rats using multispectral imaging flow cytometry (IFC, which combines the high-throughput advantage of flow cytometry with the morphological and fluorescence features derived from microscopy. This method provides both quantitative analysis of EBIs, as well as structural and morphological details of the central macrophages and associated cells. Importantly, the images, combined with quantitative software features, can be used to evaluate co-expression of phenotypic markers which is crucial since some antigens used to identify macrophages (e.g., F4/80 and CD11b can be expressed on non-erythroid cells associated with the islands instead of, or in addition to the central macrophage itself. We have used this method to analyze native EBIs from different hematopoietic tissues and evaluated the expression of several markers that have been previously reported to be expressed on EBI macrophages. We

  5. CD4 and CD8 T cell responses to the M. tuberculosis Ag85B-TB10.4 promoted by adjuvanted subunit, adenovector or heterologous prime boost vaccination

    DEFF Research Database (Denmark)

    Elvang, Tara; Christensen, Jan P; Billeskov, Rolf

    2009-01-01

    recruited to the site of infection, at the onset of infection. However, compared to CD8 T cells, CD4 T cells showed more extensive recruitment and were the main T cell subset proliferating at the site of infection. CONCLUSIONS/SIGNIFICANCE: Heterologous prime boost based on H4, produced an additive effect...

  6. Leucine supplementation attenuates macrophage foam-cell formation: Studies in humans, mice, and cultured macrophages.

    Science.gov (United States)

    Grajeda-Iglesias, Claudia; Rom, Oren; Hamoud, Shadi; Volkova, Nina; Hayek, Tony; Abu-Saleh, Niroz; Aviram, Michael

    2018-02-05

    Whereas atherogenicity of dietary lipids has been largely studied, relatively little is known about the possible contribution of dietary amino acids to macrophage foam-cell formation, a hallmark of early atherogenesis. Recently, we showed that leucine has antiatherogenic properties in the macrophage model system. In this study, an in-depth investigation of the role of leucine in macrophage lipid metabolism was conducted by supplementing humans, mice, or cultured macrophages with leucine. Macrophage incubation with serum obtained from healthy adults supplemented with leucine (5 g/d, 3 weeks) significantly decreased cellular cholesterol mass by inhibiting the rate of cholesterol biosynthesis and increasing cholesterol efflux from macrophages. Similarly, leucine supplementation to C57BL/6 mice (8 weeks) resulted in decreased cholesterol content in their harvested peritoneal macrophages (MPM) in relation with reduced cholesterol biosynthesis rate. Studies in J774A.1 murine macrophages revealed that leucine dose-dependently decreased cellular cholesterol and triglyceride mass. Macrophages treated with leucine (0.2 mM) showed attenuated uptake of very low-density lipoproteins and triglyceride biosynthesis rate, with a concurrent down-regulation of diacylglycerol acyltransferase-1, a key enzyme catalyzing triglyceride biosynthesis in macrophages. Similar effects were observed when macrophages were treated with α-ketoisocaproate, a key leucine metabolite. Finally, both in vivo and in vitro leucine supplementation significantly improved macrophage mitochondrial respiration and ATP production. The above studies, conducted in human, mice, and cultured macrophages, highlight a protective role for leucine attenuating macrophage foam-cell formation by mechanisms related to the metabolism of cholesterol, triglycerides, and energy production. © 2018 BioFactors, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

  7. Primed Mycobacterial Uveitis (PMU): Histologic and Cytokine Characterization of a Model of Uveitis in Rats.

    Science.gov (United States)

    Pepple, Kathryn L; Rotkis, Lauren; Van Grol, Jennifer; Wilson, Leslie; Sandt, Angela; Lam, Deborah L; Carlson, Eric; Van Gelder, Russell N

    2015-12-01

    The purpose of this study was to compare the histologic features and cytokine profiles of experimental autoimmune uveitis (EAU) and a primed mycobacterial uveitis (PMU) model in rats. In Lewis rats, EAU was induced by immunization with interphotoreceptor binding protein peptide, and PMU was induced by immunization with a killed mycobacterial extract followed by intravitreal injection of the same extract. Clinical course, histology, and the cytokine profiles of the aqueous and vitreous were compared using multiplex bead fluorescence immunoassays. Primed mycobacterial uveitis generates inflammation 2 days after intravitreal injection and resolves spontaneously 14 days later. CD68+ lymphocytes are the predominant infiltrating cells and are found in the anterior chamber, surrounding the ciliary body and in the vitreous. In contrast to EAU, no choroidal infiltration or retinal destruction is noted. At the day of peak inflammation, C-X-C motif ligand 10 (CXCL10), IL-1β, IL-18, and leptin were induced in the aqueous of both models. Interleukin-6 was induced 2-fold in the aqueous of PMU but not EAU. Cytokines elevated in the aqueous of EAU exclusively include regulated on activation, normal T cell expressed and secreted (RANTES), lipopolysaccharide-induced CXC chemokine (LIX), growth-related oncogene/keratinocyte chemokine (GRO/KC), VEGF, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and IL-17A. In the vitreous, CXCL10, GRO/KC, RANTES, and MIP-1α were elevated in both models. Interleukin-17A and IL-18 were elevated exclusively in EAU. Primed mycobacterial uveitis generates an acute anterior and intermediate uveitis without retinal involvement. Primed mycobacterial uveitis has a distinct proinflammatory cytokine profile compared with EAU, suggesting PMU is a good complementary model for study of immune-mediated uveitis. CXCL10, a proinflammatory cytokine, was increased in the aqueous and vitreous of both models and may be a

  8. Buffering effect of money priming on negative emotions—An ERP study.

    Science.gov (United States)

    Ma, Qingguo; Hu, Yue; Pei, Guanxiong; Xiang, Ting

    2015-10-08

    Recent studies have accumulated evidences that merely reminding people of money could lead to behavioral changes including alleviating both physical pain and social distress. However, the underlying neural mechanism regarding such pain-buffering effect of money is not clear. In this paper, we applied event-related potentials (ERP) to investigate the neural effect of money reminders on induced negative emotions. Subjects were first primed of money images and subsequently viewing unpleasant pictures, while EEG was recorded. Behavioral results suggested a reduced sensitivity to unpleasant pictures after participants being reminded of money. ERP data showed that money priming, compared to neutral priming, generated a larger N2 in frontal and posterior areas, reflecting an endogenous mental conflict and the recruitment of attention resources, and a smaller late positive potential (LPP) in parietal and occipital regions, indicating a regulating process of negative emotions. Additionally, how brain responded to money and neutral stimuli were also examined, indexed by "N170-P2" complex. This study provided additional neurophysiological evidences to support previous behavioral researches on money priming and discussed the two separated neural dynamic stages involved in emotion regulation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Suppressive effects of ketamine on macrophage functions

    International Nuclear Information System (INIS)

    Chang Yi; Chen, T.-L.; Sheu, J.-R.; Chen, R.-M.

    2005-01-01

    Ketamine is an intravenous anesthetic agent. Clinically, induction of anesthesia with ketamine can cause immunosuppression. Macrophages play important roles in host defense. In this study, we attempted to evaluate the effects of ketamine on macrophage functions and its possible mechanism using mouse macrophage-like Raw 264.7 cells as the experimental model. Exposure of macrophages to 10 and 100 μM ketamine, which correspond to 0.1 and 1 times the clinically relevant concentration, for 1, 6, and 24 h had no effect on cell viability or lactate dehydrogenase release. When the administered concentration reached 1000 μM, ketamine caused a release of lactate dehydrogenase and cell death. Ketamine, at 10 and 100 μM, did not affect the chemotactic activity of macrophages. Administration of 1000 μM ketamine in macrophages resulted in a decrease in cell migration. Treatment of macrophages with ketamine reduced phagocytic activities. The oxidative ability of macrophages was suppressed by ketamine. Treatment with lipopolysaccharide induced TNF-α, IL-1β, and IL-6 mRNA in macrophages. Administration of ketamine alone did not influence TNF-α, IL-1β, or IL-6 mRNA production. Meanwhile, cotreatment with ketamine and lipopolysaccharide significantly inhibited lipopolysaccharide-induced TNF-α, IL-1β, and IL-6 mRNA levels. Exposure to ketamine led to a decrease in the mitochondrial membrane potential. However, the activity of mitochondrial complex I NADH dehydrogenase was not affected by ketamine. This study shows that a clinically relevant concentration of ketamine (100 μM) can suppress macrophage function of phagocytosis, its oxidative ability, and inflammatory cytokine production possibly via reduction of the mitochondrial membrane potential instead of direct cellular toxicity

  10. 40 CFR 5.310 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Recruitment. 5.310 Section 5.310... in Admission and Recruitment Prohibited § 5.310 Recruitment. (a) Nondiscriminatory recruitment. A... recruitment and admission of students. A recipient may be required to undertake additional recruitment efforts...

  11. 43 CFR 41.310 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Recruitment. 41.310 Section 41.310 Public... in Admission and Recruitment Prohibited § 41.310 Recruitment. (a) Nondiscriminatory recruitment. A... recruitment and admission of students. A recipient may be required to undertake additional recruitment efforts...

  12. 14 CFR 1253.310 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Recruitment. 1253.310 Section 1253.310... in Admission and Recruitment Prohibited § 1253.310 Recruitment. (a) Nondiscriminatory recruitment. A... recruitment and admission of students. A recipient may be required to undertake additional recruitment efforts...

  13. 6 CFR 17.310 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Recruitment. 17.310 Section 17.310 Domestic... in Admission and Recruitment Prohibited § 17.310 Recruitment. (a) Nondiscriminatory recruitment. A... recruitment and admission of students. A recipient may be required to undertake additional recruitment efforts...

  14. 41 CFR 101-4.310 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Recruitment. 101-4.310... Admission and Recruitment Prohibited § 101-4.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient... recruitment and admission of students. A recipient may be required to undertake additional recruitment efforts...

  15. 15 CFR 8a.310 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Recruitment. 8a.310 Section 8a.310... in Admission and Recruitment Prohibited § 8a.310 Recruitment. (a) Nondiscriminatory recruitment. A... recruitment and admission of students. A recipient may be required to undertake additional recruitment efforts...

  16. 28 CFR 54.310 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Recruitment. 54.310 Section 54.310... in Admission and Recruitment Prohibited § 54.310 Recruitment. (a) Nondiscriminatory recruitment. A... recruitment and admission of students. A recipient may be required to undertake additional recruitment efforts...

  17. Proteinase activated receptor 1 mediated fibrosis in a mouse model of liver injury: a role for bone marrow derived macrophages.

    Directory of Open Access Journals (Sweden)

    Yiannis N Kallis

    Full Text Available Liver fibrosis results from the co-ordinated actions of myofibroblasts and macrophages, a proportion of which are of bone marrow origin. The functional effect of such bone marrow-derived cells on liver fibrosis is unclear. We examine whether changing bone marrow genotype can down-regulate the liver's fibrotic response to injury and investigate mechanisms involved. Proteinase activated receptor 1 (PAR1 is up-regulated in fibrotic liver disease in humans, and deficiency of PAR1 is associated with reduced liver fibrosis in rodent models. In this study, recipient mice received bone marrow transplantation from PAR1-deficient or wild-type donors prior to carbon tetrachloride-induced liver fibrosis. Bone marrow transplantation alone from PAR1-deficient mice was able to confer significant reductions in hepatic collagen content and activated myofibroblast expansion on wild-type recipients. This effect was associated with a decrease in hepatic scar-associated macrophages and a reduction in macrophage recruitment from the bone marrow. In vitro, PAR1 signalling on bone marrow-derived macrophages directly induced their chemotaxis but did not stimulate proliferation. These data suggest that the bone marrow can modulate the fibrotic response of the liver to recurrent injury. PAR1 signalling can contribute to this response by mechanisms that include the regulation of macrophage recruitment.

  18. Human Resources Marketing and Recruiting: Essentials of Digital Recruiting

    CERN Document Server

    Purvis, James

    2016-01-01

    This chapter will cover digital recruitment from its definition thru to its history in recruitment and trends. The subject itself could cover an entire book or an entire module at university, so this chapter will broadly touch upon the key elements and considerations. Under cultural perspective, the recruitment life cycle will be broken down into its individual parts, and digital solutions will be examined for each individual part of the process together with the impact this has on the knowledge and challenges for the manager and team. The economic perspective will assist in prioritizing initiatives and building a business case for the introduction of digital recruiting solutions. The risk perspective will raise awareness of the potential pitfalls and the operational perspective on the key considerations for a successful implementation. Finally, the key messages of this chapter are summarized in the Do’s and Don’ts.

  19. Sales Training for Army Recruiter Success: Interviews with Excellent Recruiters

    Science.gov (United States)

    1987-11-01

    merit of an expert modeling system of the skills and strategies used by excel- lent Army recruiters. Neurolinguistic programming (NLP) was used as the...7. AUTHOR(&) 8. CONTRACT OR GRANT NUMBER(s) Steven R. Frieman 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT, TASK U.S...Recruiting 2M AUSTIRACT (rcnttm ame r orw am nssry i Identify by block number) s-This report describes a program of research on communication strategies and

  20. Identification of Therapeutic Targets of Inflammatory Monocyte Recruitment to Modulate the Allogeneic Injury to Donor Cornea

    OpenAIRE

    Lapp, T.; Zaher, S. S.; Haas, C. T.; Becker, D. L.; Thrasivoulou, C.; Chain, B. M.; Larkin, D. F. P.; Noursadeghi, M.

    2015-01-01

    Purpose: We sought to test the hypothesis that monocytes contribute to the immunopathogenesis of corneal allograft rejection and identify therapeutic targets to inhibit monocyte recruitment. Methods: Monocytes and proinflammatory mediators within anterior chamber samples during corneal graft rejection were quantified by flow cytometry and multiplex protein assays. Lipopolysaccharide or IFN-γ stimulation of monocyte-derived macrophages (MDMs) was used to generate inflammatory conditioned me...

  1. Susceptibility of bone marrow-derived macrophages to influenza virus infection is dependent on macrophage phenotype.

    Science.gov (United States)

    Campbell, Gillian M; Nicol, Marlynne Q; Dransfield, Ian; Shaw, Darren J; Nash, Anthony A; Dutia, Bernadette M

    2015-10-01

    The role of the macrophage in influenza virus infection is complex. Macrophages are critical for resolution of influenza virus infections but implicated in morbidity and mortality in severe infections. They can be infected with influenza virus and consequently macrophage infection is likely to have an impact on the host immune response. Macrophages display a range of functional phenotypes, from the prototypical pro-inflammatory classically activated cell to alternatively activated anti-inflammatory macrophages involved in immune regulation and wound healing. We were interested in how macrophages of different phenotype respond to influenza virus infection and therefore studied the infection of bone marrow-derived macrophages (BMDMs) of classical and alternative phenotype in vitro. Our results show that alternatively activated macrophages are more readily infected and killed by the virus than classically activated. Classically activated BMDMs express the pro-inflammatory markers inducible nitric oxide synthase (iNOS) and TNF-α, and TNF-α expression was further upregulated following infection. Alternatively activated macrophages express Arginase-1 and CD206; however, following infection, expression of these markers was downregulated whilst expression of iNOS and TNF-α was upregulated. Thus, infection can override the anti-inflammatory state of alternatively activated macrophages. Importantly, however, this results in lower levels of pro-inflammatory markers than those produced by classically activated cells. Our results showed that macrophage phenotype affects the inflammatory macrophage response following infection, and indicated that modulating the macrophage phenotype may provide a route to develop novel strategies to prevent and treat influenza virus infection.

  2. Functional role of monocytes and macrophages for the inflammatory response in acute liver injury

    Directory of Open Access Journals (Sweden)

    Henning W Zimmermann

    2012-10-01

    Full Text Available Different etiologies such as drug toxicity, acute viral hepatitis B or acetaminophen poisoning can cause acute liver injury (ALI or even acute liver failure (ALF. Excessive cell death of hepatocytes in the liver is known to result in a strong hepatic inflammation. Experimental murine models of liver injury highlighted the importance of hepatic macrophages, so-called Kupffer cells, for initiating and driving this inflammatory response by releasing proinflammatory cytokines and chemokines including tumor necrosis factor (TNF, interleukin-6 (IL-6, IL-1-beta or monocyte chemoattractant protein 1 (MCP-1, CCL2 as well as activating other non-parenchymal liver cells, e.g. endothelial or hepatic stellate cells (HSC. Many of these proinflammatory mediators can trigger hepatocytic cell death pathways, e.g. via caspase activation, but also activate protective signaling pathways, e.g. via nuclear factor kappa B (NF-kB. Recent studies in mice demonstrated that these macrophage actions largely depend on the recruitment of monocytes into the liver, namely of the inflammatory Ly6c+ (Gr1+ monocyte subset as precursors of tissue macrophages. The chemokine receptor CCR2 and its ligand MCP-1/CCL2 promote monocyte subset infiltration upon liver injury. In contrast, the chemokine receptor CX3CR1 and its ligand fractalkine (CX3CL1 are important negative regulators of monocyte infiltration by controlling their survival and differentiation into functionally diverse macrophage subsets upon injury. The recently identified cellular and molecular pathways for monocyte subset recruitment, macrophage differentiation and interactions with other hepatic cell types in the injured liver may therefore represent interesting novel targets for future therapeutic approaches in ALF.

  3. Seeing and Being Green? The Effect of Money Priming on Willingness to Perform Sustainable Actions, Social Connectedness, and Prosociality.

    Science.gov (United States)

    Capaldi, Colin A; Zelenski, John M

    2016-01-01

    This investigation attempted to conceptually replicate/extend research that suggests that reminders of money can inhibit prosociality, promote self-sufficiency, and influence political beliefs. Based on these results, we hypothesized that money primes would decrease willingness to engage in sustainable actions. We also predicted that people would distribute points less prosocially and feel less socially connected when money was primed. Individuals were recruited from an undergraduate participant pool and MTurk. Meta-analytic results across the two samples revealed that money priming did not have a significant impact on willingness to act sustainably, but it did cause participants to distribute points less prosocially and report lower social connectedness than individuals in the control condition. While effects were smaller than those reported in Vohs, Mead, and Goode (2006), this study still offers support for the detrimental impact of reminders of money on interpersonal relations.

  4. Priming involuntary autobiographical memories in the lab.

    Science.gov (United States)

    Barzykowski, Krystian; Niedźwieńska, Agnieszka

    2018-02-01

    Involuntary autobiographical memories (IAMs) are recollections of personal past that frequently and spontaneously occur in daily life. Initial studies by Mace (2005) showed that deliberately reminiscing about a certain lifetime period (e.g., high school) significantly increased the number of different IAMs from the same period in subsequent days, suggesting that priming may play a significant role in the retrieval of IAMs in everyday life. In the present study, we used a modified experimental paradigm, originally used by Schlagman and Kvavilashvili (2008), to study IAMs under well-controlled laboratory conditions. Participants completed a monotonous vigilance task twice and reported the occurrence of any spontaneous thoughts that were later classed as IAMs or other thoughts. Priming was manipulated by having experimental participants reminiscing about high school period between the two vigilance tasks and control participants playing simple games. Results showed that participants in the experimental group reported IAMs relating to high school period more frequently during the second vigilance task than those in the control group. In the experimental group, the number of high school memories was marginally higher in the second vigilance task compared to the first vigilance task with the medium effect size, but this within subjects effect was not significant in the control group. Finally, priming also enhanced the retrieval of more remote IAMs in the experimental group compared to the control group. These results suggest that priming may play a significant role in the activation and recall of IAMs and open up interesting avenues for future research.

  5. Colorimetry and prime colours--a theorem.

    Science.gov (United States)

    Hornaes, Hans Petter; Wold, Jan Henrik; Farup, Ivar

    2005-08-01

    Human colour vision is the result of a complex process involving topics ranging from physics of light to perception. Whereas the diversity of light entering the eye in principle span an infinite-dimensional vector space in terms of the spectral power distributions, the space of human colour perceptions is three dimensional. One important consequence of this is that a variety of colours can be visually matched by a mixture of only three adequately chosen reference lights. It has been observed that there exists one particular set of monochromatic reference lights that, according to a certain definition, is optimal for producing colour matches. These reference lights are commonly denoted prime colours. In the present paper, we intend to rigorously show that the existence of prime colours is not particular to the human visual system as sometimes stated, but rather an algebraic consequence of the manner in which a kind of colorimetric functions called colour-matching functions are defined and transformed. The solution is based on maximisation of a determinant determining the gamut size of the colour space spanned by the prime colours. Cramer's rule for solving a set of linear equations is an essential part of the proof. By means of examples, it is shown that mathematically the optimal set of reference lights is not unique in general, and that the existence of a maximum determinant is not a necessary condition for the existence of prime colours.

  6. Maple Explorations, Perfect Numbers, and Mersenne Primes

    Science.gov (United States)

    Ghusayni, B.

    2005-01-01

    Some examples from different areas of mathematics are explored to give a working knowledge of the computer algebra system Maple. Perfect numbers and Mersenne primes, which have fascinated people for a very long time and continue to do so, are studied using Maple and some questions are posed that still await answers.

  7. Phonological Priming and Cohort Effects in Toddlers

    Science.gov (United States)

    Mani, Nivedita; Plunkett, Kim

    2011-01-01

    Adult word recognition is influenced by prior exposure to phonologically or semantically related words ("cup" primes "cat" or "plate") compared to unrelated words ("door"), suggesting that words are organised in the adult lexicon based on their phonological and semantic properties and that word recognition implicates not just the heard word, but…

  8. Random reward priming is task-contingent

    DEFF Research Database (Denmark)

    Ásgeirsson, Árni Gunnar; Kristjánsson, Árni

    2014-01-01

    Consistent financial reward of particular features influences the allocation of visual attention in many ways. More surprising are 1-trial reward priming effects on attention where reward schedules are random and reward on one trial influences attentional allocation on the next. Those findings...

  9. Method for priming and DNA sequencing

    Energy Technology Data Exchange (ETDEWEB)

    Mugasimangalam, R.C.; Ulanovsky, L.E.

    1997-12-01

    A method is presented for improving the priming specificity of an oligonucleotide primer that is non-unique in a nucleic acid template which includes selecting a continuous stretch of several nucleotides in the template DNA where one of the four bases does not occur in the stretch. This also includes bringing the template DNA in contract with a non-unique primer partially or fully complimentary to the sequence immediately upstream of the selected sequence stretch. This results in polymerase-mediated differential extension of the primer in the presence of a subset of deoxyribonucleotide triphosphates that does not contain the base complementary to the base absent in the selected sequence stretch. These reactions occur at a temperature sufficiently low for allowing the extension of the non-unique primer. The method causes polymerase-mediated extension reactions in the presence of all four natural deoxyribonucleotide triphosphates or modifications. At this high temperature discrimination occurs against priming sites of the non-unique primer where the differential extension has not made the primer sufficiently stable to prime. However, the primer extended at the selected stretch is sufficiently stable to prime.

  10. MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset.

    Directory of Open Access Journals (Sweden)

    Hannelie Korf

    Full Text Available Macrophages contribute in the initiation and progression of insulitis during type 1 diabetes (T1D. However, the mechanisms governing their recruitment into the islets as well as the manner of retention and activation are incompletely understood. Here, we investigated a role for macrophage migration inhibitory factor (MIF and its transmembrane receptor, CD74, in the progression of T1D. Our data indicated elevated MIF concentrations especially in long-standing T1D patients and mice. Additionally, NOD mice featured increased MIF gene expression and CD74+ leukocyte frequencies in the pancreas. We identified F4/80+ macrophages as the main immune cells in the pancreas expressing CD74 and showed that MIF antagonism of NOD macrophages prevented their activation-induced cytokine production. The physiological importance was highlighted by the fact that inhibition of MIF delayed the onset of autoimmune diabetes in two different diabetogenic T cell transfer models. Mechanistically, macrophages pre-conditioned with the MIF inhibitor featured a refractory capacity to trigger T cell activation by keeping them in a naïve state. This study underlines a possible role for MIF/CD74 signaling pathways in promoting macrophage-mediated inflammation in T1D. As therapies directed at the MIF/CD74 pathway are in clinical development, new opportunities may be proposed for arresting T1D progression.

  11. Elastin-derived peptides promote abdominal aortic aneurysm formation by modulating M1/M2 macrophage polarization1

    Science.gov (United States)

    Dale, Matthew A; Xiong, Wanfen; Carson, Jeffrey S; Suh, Melissa K; Karpisek, Andrew D.; Meisinger, Trevor M.; Casale, George P.; Baxter, B. Timothy

    2016-01-01

    Abdominal aortic aneurysm (AAA) is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix (ECM) degradation. Damage to elastin in the ECM results in release of elastin-derived peptides (EDPs), which are chemotactic for inflammatory cells such as monocytes. Their effect on macrophage polarization is less well known. Pro-inflammatory M1 macrophages initially are recruited to sites of injury but, if their effects are prolonged, they can lead to chronic inflammation that prevents normal tissue repair. Conversely, anti-inflammatory M2 macrophages reduce inflammation and aid in wound healing. Thus, a proper M1/M2 ratio is vital for tissue homeostasis. AAA tissue reveals a high M1/M2 ratio where pro-inflammatory cells and their associated markers dominate. In the present study, in vitro treatment of bone marrow-derived macrophages with EDPs induced M1 macrophage polarization. By using C57Bl/6 mice, antibody-mediated neutralization of EDPs reduced aortic dilation, matrix metalloproteinase activity, and pro-inflammatory cytokine expression at early and late time points after aneurysm induction. Furthermore, direct manipulation of the M1/M2 balance altered aortic dilation. Injection of M2 polarized macrophages reduced aortic dilation after aneurysm induction. EDPs promoted a pro-inflammatory environment in aortic tissue by inducing M1 polarization and neutralization of EDPs attenuated aortic dilation. The M1/M2 imbalance is vital to aneurysm formation. PMID:27183603

  12. HIV-1 Latency in Monocytes/Macrophages

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    2014-04-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host.

  13. Inflammatory Macrophages Promotes Development of Diabetic Encephalopathy.

    Science.gov (United States)

    Wang, Beiyun; Miao, Ya; Zhao, Zhe; Zhong, Yuan

    2015-01-01

    Diabetes and Alzheimer's disease are often associated with each other, whereas the relationship between two diseases is ill-defined. Although hyperglycemia during diabetes is a major cause of encephalopathy, diabetes may also cause chronic inflammatory complications including peripheral neuropathy. Hence the role and the characteristics of inflammatory macrophages in the development of diabetic encephalopathy need to be clarified. Diabetes were induced in mice by i.p. injection of streptozotocin (STZ). Two weeks after STZ injection and confirmation of development of diabetes, inflammatory macrophages were eliminated by i.p. injection of 20µg saporin-conjugated antibody against a macrophage surface marker CD11b (saporin-CD11b) twice per week, while a STZ-treated group received injection of rat IgG of same frequency as a control. The effects of macrophage depletion on brain degradation markers, brain malondialdehyde (MDA), catalase, superoxidase anion-positive cells and nitric oxide (NO) were measured. Saporin-CD11b significantly reduced inflammatory macrophages in brain, without affecting mouse blood glucose, serum insulin, glucose responses and beta cell mass. However, reduced brain macrophages significantly inhibited the STZ-induced decreases in brain MDA, catalase and superoxidase anion-positive cells, and the STZ-induced decreases in brain NO. Inflammatory macrophages may promote development of diabetic encephalopathy. © 2015 S. Karger AG, Basel.

  14. DNA polymerase preference determines PCR priming efficiency.

    Science.gov (United States)

    Pan, Wenjing; Byrne-Steele, Miranda; Wang, Chunlin; Lu, Stanley; Clemmons, Scott; Zahorchak, Robert J; Han, Jian

    2014-01-30

    Polymerase chain reaction (PCR) is one of the most important developments in modern biotechnology. However, PCR is known to introduce biases, especially during multiplex reactions. Recent studies have implicated the DNA polymerase as the primary source of bias, particularly initiation of polymerization on the template strand. In our study, amplification from a synthetic library containing a 12 nucleotide random portion was used to provide an in-depth characterization of DNA polymerase priming bias. The synthetic library was amplified with three commercially available DNA polymerases using an anchored primer with a random 3' hexamer end. After normalization, the next generation sequencing (NGS) results of the amplified libraries were directly compared to the unamplified synthetic library. Here, high throughput sequencing was used to systematically demonstrate and characterize DNA polymerase priming bias. We demonstrate that certain sequence motifs are preferred over others as primers where the six nucleotide sequences at the 3' end of the primer, as well as the sequences four base pairs downstream of the priming site, may influence priming efficiencies. DNA polymerases in the same family from two different commercial vendors prefer similar motifs, while another commercially available enzyme from a different DNA polymerase family prefers different motifs. Furthermore, the preferred priming motifs are GC-rich. The DNA polymerase preference for certain sequence motifs was verified by amplification from single-primer templates. We incorporated the observed DNA polymerase preference into a primer-design program that guides the placement of the primer to an optimal location on the template. DNA polymerase priming bias was characterized using a synthetic library amplification system and NGS. The characterization of DNA polymerase priming bias was then utilized to guide the primer-design process and demonstrate varying amplification efficiencies among three commercially

  15. HSV-1-induced chemokine expression via IFI16-dependent and IFI16-independent pathways in human monocyte-derived macrophages

    DEFF Research Database (Denmark)

    Søby, Stine; Laursen, Rune R; Østergaard, Lars Jørgen

    2012-01-01

    ABSTRACT: BACKGROUND: Innate recognition is essential in the antiviral response against infection by herpes simplex virus (HSV). Chemokines are important for control of HSV via recruitment of natural killer cells, T lymphocytes, and antigen-presenting cells. We previously found that early HSV-1......-mediated chemokine responses are not dependent on TLR2 and TLR9 in human macrophages. Here, we investigated the role of the recently identified innate IFN-inducible DNA receptor IFI16 during HSV-1 infection in human macrophages. METHODS: Peripheral blood mononuclear cells were purified from buffy coats...

  16. On prime ideals and associated spectrum of BCK-algebras

    International Nuclear Information System (INIS)

    Ahsan, J.; Thaheem, A.B.; Deeba, E.Y.

    1989-07-01

    In this paper we study prime ideals and define the spectrum of a bounded commutative BCK-algebra. We also obtain a characterization of minimal prime (lattice) ideals of these algebras. (author). 8 refs, 4 tabs

  17. Semantic priming without association: a meta-analytic review.

    Science.gov (United States)

    Lucas, M

    2000-12-01

    A meta-analysis of 26 studies indicated that automatic semantic priming can occur without association. Priming did not vary substantially with differences in variables that affect automatic versus strategic processing, such as time spent processing the prime and target, relationship proportion, and task (except that average effects were smaller in the naming task). Although category coordinates were investigated in the majority of studies, synonyms, antonyms, and script relations also demonstrated priming; functional relations showed greater priming, and essential and perceptual relations showed less. The average effect size for semantic priming was smaller than that for associative priming, suggesting that there is an "associative boost" from adding an associative relationship to a semantic one. The implications of these findings for the modularity thesis and for models of semantic priming are discussed.

  18. A concerted kinase interplay identifies PPARgamma as a molecular target of ghrelin signaling in macrophages.

    Directory of Open Access Journals (Sweden)

    Annie Demers

    2009-11-01

    Full Text Available The peroxisome proliferator-activator receptor PPARgamma plays an essential role in vascular biology, modulating macrophage function and atherosclerosis progression. Recently, we have described the beneficial effect of combined activation of the ghrelin/GHS-R1a receptor and the scavenger receptor CD36 to induce macrophage cholesterol release through transcriptional activation of PPARgamma. Although the interplay between CD36 and PPARgamma in atherogenesis is well recognized, the contribution of the ghrelin receptor to regulate PPARgamma remains unknown. Here, we demonstrate that ghrelin triggers PPARgamma activation through a concerted signaling cascade involving Erk1/2 and Akt kinases, resulting in enhanced expression of downstream effectors LXRalpha and ABC sterol transporters in human macrophages. These effects were associated with enhanced PPARgamma phosphorylation independently of the inhibitory conserved serine-84. Src tyrosine kinase Fyn was identified as being recruited to GHS-R1a in response to ghrelin, but failure of activated Fyn to enhance PPARgamma Ser-84 specific phosphorylation relied on the concomitant recruitment of docking protein Dok-1, which prevented optimal activation of the Erk1/2 pathway. Also, substitution of Ser-84 preserved the ghrelin-induced PPARgamma activity and responsiveness to Src inhibition, supporting a mechanism independent of Ser-84 in PPARgamma response to ghrelin. Consistent with this, we found that ghrelin promoted the PI3-K/Akt pathway in a Galphaq-dependent manner, resulting in Akt recruitment to PPARgamma, enhanced PPARgamma phosphorylation and activation independently of Ser-84, and increased expression of LXRalpha and ABCA1/G1. Collectively, these results illustrate a complex interplay involving Fyn/Dok-1/Erk and Galphaq/PI3-K/Akt pathways to transduce in a concerted manner responsiveness of PPARgamma to ghrelin in macrophages.

  19. Recruiting for Prior Service Market

    National Research Council Canada - National Science Library

    Thomas, Brian A; Givens, Eric

    2008-01-01

    ...) market based on data from: * DMDC (All services) * IRR (HRC-St. Louis) * AC/RC transition (HRC-Alexandria); 2) To recommend possible recruiting pools of applicants from the analyzed market data...

  20. Information networks and worker recruitment

    NARCIS (Netherlands)

    Schram, A.; Brandts, J.; Gërxhani, K.

    2007-01-01

    This paper studies experimentally how the existence of social information networks affects the ways in which firms recruit new personnel. Through such networks firms learn about prospective employees' performance in previous jobs. Assuming individualistic preferences social networks are predicted

  1. Student Recruitment: The Hard Sell?

    Science.gov (United States)

    McAdams, Tony

    1975-01-01

    Presents the pros and cons concerning advertising for recruitment using three modes of analyses - economics, ethics, and law. The author concludes that advertising is an invaluable technique for information dispersal in higher education. (Author/PG)

  2. Macrophages and Uveitis in Experimental Animal Models

    Directory of Open Access Journals (Sweden)

    Salvador Mérida

    2015-01-01

    Full Text Available Resident and infiltrated macrophages play relevant roles in uveitis as effectors of innate immunity and inductors of acquired immunity. They are major effectors of tissue damage in uveitis and are also considered to be potent antigen-presenting cells. In the last few years, experimental animal models of uveitis have enabled us to enhance our understanding of the leading role of macrophages in eye inflammation processes, including macrophage polarization in experimental autoimmune uveoretinitis and the major role of Toll-like receptor 4 in endotoxin-induced uveitis. This improved knowledge should guide advantageous iterative research to establish mechanisms and possible therapeutic targets for human uveitis resolution.

  3. Action verbs are processed differently in metaphorical and literal sentences depending on the semantic match of visual primes

    Directory of Open Access Journals (Sweden)

    Melissa eTroyer

    2014-12-01

    Full Text Available Language comprehension requires rapid and flexible access to information stored in long-term memory, likely influenced by activation of rich world knowledge and by brain systems that support the processing of sensorimotor content. We hypothesized that while literal language about biological motion might rely on neurocognitive representations of biological motion specific to the details of the actions described, metaphors rely on more generic representations of motion. In a priming and self-paced reading paradigm, participants saw video clips or images of (a an intact point-light walker or (b a scrambled control and read sentences containing literal or metaphoric uses of biological motion verbs either closely or distantly related to the depicted action (walking. We predicted that reading times for literal and metaphorical sentences would show differential sensitivity to the match between the verb and the visual prime. In Experiment 1, we observed interactions between the prime type (walker or scrambled video and the verb type (close or distant match for both literal and metaphorical sentences, but with strikingly different patterns. We found no difference in the verb region of literal sentences for Close-Match verbs after walker or scrambled motion primes, but Distant-Match verbs were read more quickly following walker primes. For metaphorical sentences, the results were roughly reversed, with Distant-Match verbs being read more slowly following a walker compared to scrambled motion. In Experiment 2, we observed a similar pattern following still image primes, though critical interactions emerged later in the sentence. We interpret these findings as evidence for shared recruitment of cognitive and neural mechanisms for processing visual and verbal biological motion information. Metaphoric language using biological motion verbs may recruit neurocognitive mechanisms similar to those used in processing literal language but be represented in a less

  4. Major role of adipocyte prostaglandin E2 in lipolysis-induced macrophage recruitment

    Czech Academy of Sciences Publication Activity Database

    Hu, XQ.; Cifarelli, V.; Sun, SS.; Kuda, Ondřej; Abumrad, N. A.; Su, X.

    2016-01-01

    Roč. 57, č. 4 (2016), s. 663-673 ISSN 0022-2275 R&D Projects: GA MŠk(CZ) LH14040 Institutional support: RVO:67985823 Keywords : adipose tissue * cyclooxygenase * eicosanoids * extracellular signal-regulated kinase * fatty acid * inflammation * lipase Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.810, year: 2016

  5. Recruiting for Prior Service Market

    Science.gov (United States)

    2008-06-01

    perceptions, expectations and issues for re-enlistment • Develop potential marketing and advertising tactics and strategies targeted to the defined...01 JUN 2008 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Recruiting for Prior Service Market 5a. CONTRACT NUMBER 5b. GRANT...Command First Handshake to First Unit of Assignment An Army of One Proud to Be e e to Serve Recruiting for Prior Service Market MAJ Eric Givens / MAJ Brian

  6. Dexamethasone targeted directly to macrophages induces macrophage niches that promote erythroid expansion

    DEFF Research Database (Denmark)

    Falchi, Mario; Varricchio, Lilian; Martelli, Fabrizio

    2015-01-01

    Cultures of human CD34(pos) cells stimulated with erythroid growth factors plus dexamethasone, a model for stress erythropoiesis, generate numerous erythroid cells plus a few macrophages (approx. 3%; 3:1 positive and negative for CD169). Interactions occurring between erythroblasts and macrophages...... in these cultures and the biological effects associated with these interactions were documented by live phase-contrast videomicroscopy. Macrophages expressed high motility interacting with hundreds/thousands of erythroblasts per hour. CD169(pos) macrophages established multiple rapid 'loose' interactions...... with proerythroblasts leading to formation of transient erythroblastic island-like structures. By contrast, CD169(neg) macrophages established 'tight' interactions with mature erythroblasts and phagocytosed these cells. 'Loose' interactions of CD169(pos) macrophages were associated with proerythroblast cytokinesis (the...

  7. Tumor associated CD70 expression is involved in promoting tumor migration and macrophage infiltration in GBM.

    Science.gov (United States)

    Ge, Haitao; Mu, Luyan; Jin, Linchun; Yang, Changlin; Chang, Yifan Emily; Long, Yu; DeLeon, Gabriel; Deleyrolle, Loic; Mitchell, Duane A; Kubilis, Paul S; Lu, Dunyue; Qi, Jiping; Gu, Yunhe; Lin, Zhiguo; Huang, Jianping

    2017-10-01

    Tumor migration/metastasis and immunosuppression are major obstacles in effective cancer therapy. Incidentally, these 2 hurdles usually coexist inside tumors, therefore making therapy significantly more complicated, as both oncogenic mechanisms must be addressed for successful therapeutic intervention. Our recent report highlights that the tumor expression of a TNF family member, CD70, is correlated with poor survival for primary gliomas. In this study, we investigated how CD70 expression by GBM affects the characteristics of tumor cells and the tumor microenvironment. We found that the ablation of CD70 in primary GBM decreased CD44 and SOX2 gene expression, and inhibited tumor migration, growth and the ability to attract monocyte-derived M2 macrophages in vitro. In the tumor microenvironment, CD70 was associated with immune cell infiltrates, such as T cells; myeloid-derived suppressor cells; and monocytes/macrophages based on the RNA-sequencing profile. The CD163+ macrophages were far more abundant than T cells were. This overwhelming level of macrophages was identified only in GBM and not in low-grade gliomas and normal brain specimens, implying their tumor association. CD70 was detected only on tumor cells, not on macrophages, and was highly correlated with CD163 gene expression in primary GBM. Additionally, the co-expression of the CD70 and CD163 genes was found to correlate with decreased survival for patients with primary GBM. Together, these data suggest that CD70 expression is involved in promoting tumor aggressiveness and immunosuppression via tumor-associated macrophage recruitment/activation. Our current efforts to target this molecule using chimeric antigen receptor T cells hold great potential for treating patients with GBM. © 2017 UICC.

  8. Recombinant guinea pig CCL5 (RANTES) differentially modulates cytokine production in alveolar and peritoneal macrophages.

    Science.gov (United States)

    Skwor, Troy A; Cho, Hyosun; Cassidy, Craig; Yoshimura, Teizo; McMurray, David N

    2004-12-01

    The CC chemokine ligand 5 (CCL5; regulated on activation, normal T expressed and secreted) is known to recruit and activate leukocytes; however, its role in altering the responses of host cells to a subsequent encounter with a microbial pathogen has rarely been studied. Recombinant guinea pig (rgp)CCL5 was prepared, and its influence on peritoneal and alveolar macrophage activation was examined by measuring cytokine and chemokine mRNA expression in cells stimulated with rgpCCL5 alone or exposed to rgpCCL5 prior to lipopolysaccharide (LPS) stimulation. Levels of mRNA for guinea pig tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, CCL2 (monocyte chemoattractant protein-1), and CXC chemokine ligand 8 (IL-8) were analyzed by reverse transcription followed by real-time polymerase chain reaction analysis using SYBR Green. Bioactive TNF-alpha protein concentration was measured using the L929 bioassay. Both macrophage populations displayed significant enhancement of all the genes and TNF-alpha protein levels when stimulated with rgpCCL5, except for CCL2 in alveolar macrophages. When peritoneal or alveolar macrophages were pretreated with rgpCCL5 for 2 h and then exposed to low concentrations of LPS, diminished cytokine and chemokine mRNA levels were apparent at 6 h compared with LPS alone. At the protein level, there was a reduction in TNF-alpha protein at 6 h in the CCL5-pretreated cells compared with LPS alone. These results further support a role for CCL5 in macrophage activation in addition to chemotactic properties and suggest a role in regulating the inflammatory response to LPS in the guinea pig by modulating the production of proinflammatory cytokines by macrophages.

  9. Prime time news: the influence of primed positive and negative emotion on susceptibility to false memories.

    Science.gov (United States)

    Porter, Stephen; ten Brinke, Leanne; Riley, Sean N; Baker, Alysha

    2014-01-01

    We examined the relation between emotion and susceptibility to misinformation using a novel paradigm, the ambiguous stimuli affective priming (ASAP) paradigm. Participants (N = 88) viewed ambiguous neutral images primed either at encoding or retrieval to be interpreted as either highly positive or negative (or neutral/not primed). After viewing the images, they either were asked misleading or non-leading questions. Following a delay, memory accuracy for the original images was assessed. Results indicated that any emotional priming at encoding led to a higher susceptibility to misinformation relative to priming at recall. In particular, inducing a negative interpretation of the image at encoding led to an increased susceptibility of false memories for major misinformation (an entire object not actually present in the scene). In contrast, this pattern was reversed when priming was used at recall; a negative reinterpretation of the image decreased memory distortion relative to unprimed images. These findings suggest that, with precise experimental control, the experience of emotion at event encoding, in particular, is implicated in false memory susceptibility.

  10. Australia's First Prime Ministerial Library: Past and Future

    Science.gov (United States)

    Carman-Brown, Lesley; Henderson, Kandy-Jane; Wallace, Lesley

    2005-01-01

    In creating Australia's first prime ministerial library, a new cultural institution was developed which blends professional practice from the fields of librarianship, education, archives, journalism and museums. The John Curtin Prime Ministerial Library honours the contribution of wartime prime minister John Curtin, works towards the advancement…

  11. Space-Valence Priming with Subliminal and Supraliminal Words

    Directory of Open Access Journals (Sweden)

    Ulrich eAnsorge

    2013-02-01

    Full Text Available To date it is unclear whether (1 awareness-independent non-evaluative semantic processes influence affective semantics and whether (2 awareness-independent affective semantics influence non-evaluative semantic processing. In the current study, we investigated these questions with the help of subliminal (masked primes and visible targets in a space-valence across-category congruence effect. In line with (1, we found that subliminal space prime words influenced valence classification of supraliminal target words (Experiment 1: Classifications were faster with a congruent prime (e.g., the prime ‘up’ before the target ‘happy’ than with an incongruent prime (e.g., the prime ‘up’ before the target ‘sad’. In contrast to (2, no influence of subliminal valence primes on the classification of supraliminal space targets into up- and down-words was found (Experiment 2. Control conditions showed that standard masked response-priming effects were found with both subliminal prime types, and that an across-category congruence effect was also found with supraliminal valence primes and spatial target words. The final Experiment 3 confirmed that the across-category congruence effect indeed reflected priming of target categorization of a relevant meaning category. Together, the data jointly confirmed prediction (1 that awareness-independent non-evaluative semantic priming influences valence judgments.

  12. The Nature of Affective Priming in Music and Speech

    NARCIS (Netherlands)

    Goerlich, K.S.; Witteman, J.; Schiller, N.O.; Van Heuven, V.J.; Aleman, A.; Martens, S.

    The phenomenon of affective priming has caught scientific interest for over 30 years, yet the nature of the affective priming effect remains elusive. This study investigated the underlying mechanism of cross-modal affective priming and the influence of affective incongruence in music and speech on

  13. Attentional Control and the Relatedness Proportion Effect in Semantic Priming

    Science.gov (United States)

    Hutchison, Keith A.

    2007-01-01

    In 2 experiments, participants completed both an attentional control battery (OSPAN, antisaccade, and Stroop tasks) and a modified semantic priming task. The priming task measured relatedness proportion (RP) effects within subjects, with the color of the prime indicating the probability that the to-be-named target would be related. In Experiment…

  14. Novel Word Lexicalization and the Prime Lexicality Effect

    Science.gov (United States)

    Qiao, Xiaomei; Forster, Kenneth I.

    2013-01-01

    This study investigates how newly learned words are integrated into the first-language lexicon using masked priming. Two lexical decision experiments are reported, with the aim of establishing whether newly learned words behave like real words in a masked form priming experiment. If they do, they should show a prime lexicality effect (PLE), in…

  15. Persistent Structural Priming from Language Comprehension to Language Production

    Science.gov (United States)

    Bock, Kathryn; Dell, Gary S.; Chang, Franklin; Onishi, Kristine H.

    2007-01-01

    To examine the relationship between syntactic processes in language comprehension and language production, we compared structural persistence from sentence primes that speakers heard to persistence from primes that speakers produced. [Bock, J. K., & Griffin, Z. M. (2000). The persistence of structural priming: transient activation or implicit…

  16. Stochastic resolution analysis of co-prime arrays in radar

    NARCIS (Netherlands)

    Pribic, R; Coutiño Minguez, M.A.; Leus, G.J.T.

    2016-01-01

    Resolution from co-prime arrays and from a full ULA of the size equal to the virtual size of co-prime arrays is investigated. We take into account not only the resulting beam width but also the fact that fewer measurements are acquired by co-prime arrays. This fact is relevant in compressive

  17. 48 CFR 45.501 - Prime contractor alternate locations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Prime contractor alternate... CONTRACT MANAGEMENT GOVERNMENT PROPERTY Support Government Property Administration 45.501 Prime contractor... administration from another contract administration office, for purposes of evaluating prime contractor...

  18. Arithmetically Related Ideal Topologies and the Infinitude of Primes ...

    African Journals Online (AJOL)

    algebra. Mathematics Subject Classification (1991): 11N80, 11N25, 11A41, 11T99, 13A15, 20M25 Keywords: x-ideal, topological semigroup, ideal topology, infinitude of primes, generalized primes and integers, distribution, integers, specified multiplicative constraints, primes, ideals, multiplicative ideal theory, semigroup

  19. Euclidean Primes Have the Minimum Number of Primitive Roots

    Czech Academy of Sciences Publication Activity Database

    Křížek, Michal; Somer, L.

    2008-01-01

    Roč. 12, č. 1 (2008), s. 121-127 ISSN 0972-5555 R&D Projects: GA AV ČR(CZ) IAA100190803 Institutional research plan: CEZ:AV0Z10190503 Keywords : Euclidean primes * Fermat primes * Sophie Germain primes Subject RIV: BA - General Mathematics

  20. Characterization of the antigen-specific CD4+ T cell response induced by prime-boost strategies with CAF01 and CpG adjuvants administered by the intranasal and subcutaneous routes

    Directory of Open Access Journals (Sweden)

    Annalisa eCiabattini

    2015-08-01

    Full Text Available The design of heterologous prime-boost vaccine combinations that optimally shape the immune response is of critical importance for the development of next generation vaccines. Here we tested different prime-boost combinations using the tuberculosis vaccine antigen H56 with CAF01 or CpG ODN 1821 adjuvants, administered by the parenteral and nasal routes. By using peptide-MHC class II tetramers, antigen-specific CD4+ T cells were tracked following primary and booster immunizations. Both parenteral priming with H56 plus CAF01 and nasal priming with H56 plus CpG elicited significant expansion of CD4+ tetramer-positive T cells in the spleen, however only parenterally primed cells responded to booster immunization. Subcutaneous priming with H56 and CAF01 followed by nasal boosting with H56 and CpG showed the greater expansion of CD4+ tetramer-positive T cells in the spleen and lungs compared to all the other homologous and heterologous prime-boost combinations. Nasal boosting exerted a recruitment of primed CD4+ T cells into lungs that was stronger in subcutaneously than nasally primed mice, in accordance with different chemokine receptor expression induced by primary immunization. These data demonstrate that subcutaneous priming is fundamental for eliciting CD4+ T cells that can be efficiently boosted by the nasal route and results in the recruitment of antigen-experienced cells into the lungs. Combination of different vaccine formulations and routes of delivery for priming and boosting is a strategic approach for improving and directing vaccine-induced immune responses.

  1. The response of macrophages to titanium particles is determined by macrophage polarization.

    Science.gov (United States)

    Pajarinen, Jukka; Kouri, Vesa-Petteri; Jämsen, Eemeli; Li, Tian-Fang; Mandelin, Jami; Konttinen, Yrjö T

    2013-11-01

    Aseptic loosening of total joint replacements is driven by the reaction of macrophages to foreign body particles released from the implant. It was hypothesized that the macrophages' response to these particles is dependent, in addition to particle characteristics and contaminating biomolecules, on the state of macrophage polarization as determined by the local cytokine microenvironment. To test this hypothesis we differentiated M1 and M2 macrophages from human peripheral blood monocytes and compared their responses to titanium particles using genome-wide microarray analysis and a multiplex cytokine assay. In comparison to non-activated M0 macrophages, the overall chemotactic and inflammatory responses to titanium particles were greatly enhanced in M1 macrophages and effectively suppressed in M2 macrophages. In addition, the genome-wide approach revealed several novel, potentially osteolytic, particle-induced mediators, and signaling pathway analysis suggested the involvement of toll-like and nod-like receptor signaling in particle recognition. It is concluded that the magnitude of foreign body reaction caused by titanium particles is dependent on the state of macrophage polarization. Thus, by limiting the action of M1 polarizing factors, e.g. bacterial biofilm formation, in peri-implant tissues and promoting M2 macrophage polarization by biomaterial solutions or pharmacologically, it might be possible to restrict wear-particle-induced inflammation and osteolysis. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  2. Lactobacillus priming of the respiratory tract: Heterologous immunity and protection against lethal pneumovirus infection.

    Science.gov (United States)

    Garcia-Crespo, Katia E; Chan, Calvin C; Gabryszewski, Stanislaw J; Percopo, Caroline M; Rigaux, Peter; Dyer, Kimberly D; Domachowske, Joseph B; Rosenberg, Helene F

    2013-03-01

    We showed previously that wild-type mice primed via intranasal inoculation with live or heat-inactivated Lactobacillus species were fully (100%) protected against the lethal sequelae of infection with the virulent pathogen, pneumonia virus of mice (PVM), a response that is associated with diminished expression of proinflammatory cytokines and diminished virus recovery. We show here that 40% of the mice primed with live Lactobacillus survived when PVM challenge was delayed for 5months. This robust and sustained resistance to PVM infection resulting from prior interaction with an otherwise unrelated microbe is a profound example of heterologous immunity. We undertook the present study in order to understand the nature and unique features of this response. We found that intranasal inoculation with L. reuteri elicited rapid, transient neutrophil recruitment in association with proinflammatory mediators (CXCL1, CCL3, CCL2, CXCL10, TNF-alpha and IL-17A) but not Th1 cytokines. IFNγ does not contribute to survival promoted by Lactobacillus-priming. Live L. reuteri detected in lung tissue underwent rapid clearance, and was undetectable at 24h after inoculation. In contrast, L. reuteri peptidoglycan (PGN) and L. reuteri genomic DNA (gDNA) were detected at 24 and 48h after inoculation, respectively. In contrast to live bacteria, intranasal inoculation with isolated L. reuteri gDNA elicited no neutrophil recruitment, had minimal impact on virus recovery and virus-associated production of CCL3, and provided no protection against the negative sequelae of virus infection. Isolated PGN elicited neutrophil recruitment and proinflammatory cytokines but did not promote sustained survival in response to subsequent PVM infection. Overall, further evaluation of the responses leading to Lactobacillus-mediated heterologous immunity may provide insight into novel antiviral preventive modalities. Published by Elsevier B.V.

  3. Botanical polysaccharides: macrophage immunomodulation and therapeutic potential.

    Science.gov (United States)

    Schepetkin, Igor A; Quinn, Mark T

    2006-03-01

    Botanical polysaccharides exhibit a number of beneficial therapeutic properties, and it is thought that the mechanisms involved in these effects are due to the modulation of innate immunity and, more specifically, macrophage function. In this review, we summarize our current state of understanding of the macrophage modulatory effects of botanical polysaccharides isolated from a wide array of different species of flora, including higher plants, mushrooms, lichens and algae. Overall, the primary effect of botanical polysaccharides is to enhance and/or activate macrophage immune responses, leading to immunomodulation, anti-tumor activity, wound-healing and other therapeutic effects. Furthermore, botanical and microbial polysaccharides bind to common surface receptors and induce similar immunomodulatory responses in macrophages, suggesting that evolutionarily conserved polysaccharide structural features are shared between these organisms. Thus, the evaluation of botanical polysaccharides provides a unique opportunity for the discovery of novel therapeutic agents and adjuvants that exhibit beneficial immunomodulatory properties.

  4. Epigenetic Regulation of Monocyte and Macrophage Function

    NARCIS (Netherlands)

    Hoeksema, Marten A.; de Winther, Menno P. J.

    2016-01-01

    Monocytes and macrophages are key players in tissue homeostasis and immune responses. Epigenetic processes tightly regulate cellular functioning in health and disease. Recent Advances: Recent technical developments have allowed detailed characterizations of the transcriptional circuitry underlying

  5. 10 CFR 1042.310 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Recruitment. 1042.310 Section 1042.310 Energy DEPARTMENT... Recruitment Prohibited § 1042.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 1042.300 through 1042.310 apply shall not discriminate on the basis of sex in the recruitment and admission...

  6. 45 CFR 86.23 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Recruitment. 86.23 Section 86.23 Public Welfare... in Admission and Recruitment Prohibited § 86.23 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which this subpart applies shall not discriminate on the basis of sex in the recruitment and...

  7. 49 CFR 25.310 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Recruitment. 25.310 Section 25.310 Transportation... Recruitment Prohibited § 25.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 25.300 through 25.310 apply shall not discriminate on the basis of sex in the recruitment and admission of...

  8. 22 CFR 146.310 - Recruitment.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Recruitment. 146.310 Section 146.310 Foreign... Recruitment Prohibited § 146.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 146.300 through 146.310 apply shall not discriminate on the basis of sex in the recruitment and admission...

  9. 22 CFR 229.310 - Recruitment.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Recruitment. 229.310 Section 229.310 Foreign... and Recruitment Prohibited § 229.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 229.300 through 229.310 apply shall not discriminate on the basis of sex in the recruitment and...

  10. Lack of RNase L attenuates macrophage functions.

    Directory of Open Access Journals (Sweden)

    Xin Yi

    Full Text Available Macrophages are one of the major cell types in innate immunity against microbial infection. It is believed that the expression of proinflammatory genes such as tumor necrosis factor-α (TNF-α, interleukin (IL-1β, IL-6, and cyclooxygenase-2 (Cox-2 by macrophages is also crucial for activation of both innate and adaptive immunities. RNase L is an interferon (IFN inducible enzyme which is highly expressed in macrophages. It has been demonstrated that RNase L regulates the expression of certain inflammatory genes. However, its role in macrophage function is largely unknown.Bone marrow-derived macrophages (BMMs were generated from RNase L(+/+and (-/- mice. The migration of BMMs was analyzed by using Transwell migration assays. Endocytosis and phagocytosis of macrophages were assessed by using fluorescein isothiocyanate (FITC-Dextran 40,000 and FITC-E. coli bacteria, respectively. The expression of inflammatory genes was determined by Western Blot and ELISA. The promoter activity of Cox-2 was measured by luciferase reporter assays.Lack of RNase L significantly decreased the migration of BMMs induced by M-CSF, but at a less extent by GM-CSF and chemokine C-C motif ligand-2 (CCL2. Interestingly, RNase L deficient BMMs showed a significant reduction of endocytic activity to FITC-Dextran 40,000, but no any obvious effect on their phagocytic activity to FITC-bacteria under the same condition. RNase L impacts the expression of certain genes related to cell migration and inflammation such as transforming growth factor (TGF-β, IL-1β, IL-10, CCL2 and Cox-2. Furthermore, the functional analysis of the Cox-2 promoter revealed that RNase L regulated the expression of Cox-2 in macrophages at its transcriptional level. Taken together, our findings provide direct evidence showing that RNase L contributes to innate immunity through regulating macrophage functions.

  11. miR-126-5p by direct targeting of JNK-interacting protein-2 (JIP-2) plays a key role in Theileria-infected macrophage virulence

    KAUST Repository

    Haidar, Malak

    2018-03-23

    Theileria annulata is an apicomplexan parasite that infects and transforms bovine macrophages that disseminate throughout the animal causing a leukaemia-like disease called tropical theileriosis. Using deep RNAseq of T. annulata-infected B cells and macrophages we identify a set of microRNAs induced by infection, whose expression diminishes upon loss of the hyper-disseminating phenotype of virulent transformed macrophages. We describe how infection-induced upregulation of miR-126-5p ablates JIP-2 expression to release cytosolic JNK to translocate to the nucleus and trans-activate AP-1-driven transcription of mmp9 to promote tumour dissemination. In non-disseminating attenuated macrophages miR-126-5p levels drop, JIP-2 levels increase, JNK1 is retained in the cytosol leading to decreased c-Jun phosphorylation and dampened AP-1-driven mmp9 transcription. We show that variation in miR-126-5p levels depends on the tyrosine phosphorylation status of AGO2 that is regulated by Grb2-recruitment of PTP1B. In attenuated macrophages Grb2 levels drop resulting in less PTP1B recruitment, greater AGO2 phosphorylation, less miR-126-5p associated with AGO2 and a consequent rise in JIP-2 levels. Changes in miR-126-5p levels therefore, underpin both the virulent hyper-dissemination and the attenuated dissemination of T. annulata-infected macrophages.

  12. Microparticles release by adipocytes act as "find-me" signals to promote macrophage migration.

    Directory of Open Access Journals (Sweden)

    Akiko Eguchi

    Full Text Available Macrophage infiltration of adipose tissue during weight gain is a central event leading to the metabolic complications of obesity. However, what are the mechanisms attracting professional phagocytes to obese adipose tissue remains poorly understood. Here, we demonstrate that adipocyte-derived microparticles (MPs are critical "find-me" signals for recruitment of monocytes and macrophages. Supernatants from stressed adipocytes stimulated the attraction of monocyte cells and primary macrophages. The activation of caspase 3 was required for release of these signals. Adipocytes exposed to saturated fatty acids showed marked release of MPs into the supernatant while common genetic mouse models of obesity demonstrate high levels of circulating adipocyte-derived MPs. The release of MPs was highly regulated and dependent on caspase 3 and Rho-associated kinase. Further analysis identified these MPs as a central chemoattractant in vitro and in vivo. In addition, intravenously transplanting circulating MPs from the ob/ob mice lead to activation of monocytes in circulation and adipose tissue of the wild type mice. These data identify adipocyte-derived MPs as novel "find me" signals that contributes to macrophage infiltration associated with obesity.

  13. Macrophages in intestinal homeostasis and inflammation

    Science.gov (United States)

    Bain, Calum C; Mowat, Allan McI

    2014-01-01

    The intestine contains the largest pool of macrophages in the body which are essential for maintaining mucosal homeostasis in the face of the microbiota and the constant need for epithelial renewal but are also important components of protective immunity and are involved in the pathology of inflammatory bowel disease (IBD). However, defining the biological roles of intestinal macrophages has been impeded by problems in defining the phenotype and origins of different populations of myeloid cells in the mucosa. Here, we discuss how multiple parameters can be used in combination to discriminate between functionally distinct myeloid cells and discuss the roles of macrophages during homeostasis and how these may change when inflammation ensues. We also discuss the evidence that intestinal macrophages do not fit the current paradigm that tissue-resident macrophages are derived from embryonic precursors that self-renew in situ, but require constant replenishment by blood monocytes. We describe our recent work demonstrating that classical monocytes constantly enter the intestinal mucosa and how the environment dictates their subsequent fate. We believe that understanding the factors that drive intestinal macrophage development in the steady state and how these may change in response to pathogens or inflammation could provide important insights into the treatment of IBD. PMID:24942685

  14. Macrophages and nerve fibres in peritoneal endometriosis.

    Science.gov (United States)

    Tran, Lu Vinh Phuc; Tokushige, Natsuko; Berbic, Marina; Markham, Robert; Fraser, Ian S

    2009-04-01

    Endometriosis is considered to be an inflammatory disease, and macrophages are the most numerous immune cells in endometriotic lesions. However, the mechanisms underlying the elevation of macrophages and their role in the pathogenesis and manifestations of endometriosis still remain unclear. The number of macrophages stained for CD68 in endometriotic lesions (n = 24) and in peritoneum distant from the lesions (n = 14) from women with endometriosis was compared with the number of macrophages in normal peritoneum from women without endometriosis (n = 18). Peritoneal lesions were also double-stained for CD68 and protein gene product 9.5 to study the relationship between macrophages and nerve fibres. The densities of macrophages in peritoneal endometriotic lesions and unaffected peritoneum from women with endometriosis were both significantly higher than that in normal peritoneum from women without endometriosis (P peritoneal lesions from women with endometriosis compared with normal peritoneum from women without endometriosis. These cells may well play roles in the growth and development of endometriotic lesions and in the generation of pain through interaction with nerve fibres.

  15. Spatial synchrony in cisco recruitment

    Science.gov (United States)

    Myers, Jared T.; Yule, Daniel L.; Jones, Michael L.; Ahrenstorff, Tyler D.; Hrabik, Thomas R.; Claramunt, Randall M.; Ebener, Mark P.; Berglund, Eric K.

    2015-01-01

    We examined the spatial scale of recruitment variability for disparate cisco (Coregonus artedi) populations in the Great Lakes (n = 8) and Minnesota inland lakes (n = 4). We found that the scale of synchrony was approximately 400 km when all available data were utilized; much greater than the 50-km scale suggested for freshwater fish populations in an earlier global analysis. The presence of recruitment synchrony between Great Lakes and inland lake cisco populations supports the hypothesis that synchronicity is driven by climate and not dispersal. We also found synchrony in larval densities among three Lake Superior populations separated by 25–275 km, which further supports the hypothesis that broad-scale climatic factors are the cause of spatial synchrony. Among several candidate climate variables measured during the period of larval cisco emergence, maximum wind speeds exhibited the most similar spatial scale of synchrony to that observed for cisco. Other factors, such as average water temperatures, exhibited synchrony on broader spatial scales, which suggests they could also be contributing to recruitment synchrony. Our results provide evidence that abiotic factors can induce synchronous patterns of recruitment for populations of cisco inhabiting waters across a broad geographic range, and show that broad-scale synchrony of recruitment can occur in freshwater fish populations as well as those from marine systems.

  16. Prime-Minister of Malta visits CERN

    CERN Multimedia

    2008-01-01

    The Prime-Minister of Malta, Dr Lawrence Gonzi, visited CERN and met Director-General, Robert Aymar, on 10 January. The Prime-Minister of Malta, Dr Lawrence Gonzi, and CERN Director-General, Robert Aymar, signed a cooperation agreement. Dr Gonzi was given guided tours of the CMS experiment at Point 5 in Cessy and of the LHC magnet test facility, in which his country was involved. One of the high points of the day was the signing of a cooperation agreement between CERN and the Government of the Republic of Malta, aimed at the development of scientific and technical collaboration. "I’m really enthusiastic about this agreement, which constitutes a first step towards real collaboration between the Maltese government and CERN," said Nicholas Sammut, a Maltese engineer at CERN who was present throughout the visit (on the right). See also the video.

  17. On the union of graded prime ideals

    Directory of Open Access Journals (Sweden)

    Uregen Rabia Nagehan

    2016-01-01

    Full Text Available In this paper we investigate graded compactly packed rings, which is defined as; if any graded ideal I of R is contained in the union of a family of graded prime ideals of R, then I is actually contained in one of the graded prime ideals of the family. We give some characterizations of graded compactly packed rings. Further, we examine this property on h – Spec(R. We also define a generalization of graded compactly packed rings, the graded coprimely packed rings. We show that R is a graded compactly packed ring if and only if R is a graded coprimely packed ring whenever R be a graded integral domain and h – dim R = 1.

  18. The elimination of positive priming with increasing prime duration reflects a transition from perceptual fluency to disfluency rather than bias against primed words.

    Science.gov (United States)

    Potter, Kevin W; Donkin, Chris; Huber, David E

    2018-03-01

    With immediate repetition priming of forced choice perceptual identification, short prime durations produce positive priming (i.e., priming the target leads to higher accuracy, while priming the foil leads to lower accuracy). Many theories explain positive priming following short duration primes as reflecting increased perceptual fluency for the primed target (i.e., decreased identification latency). However, most studies only examine either accuracy or response times, rather than considering the joint constraints of response times and accuracy to properly address the role of decision biases and response caution. This is a critical oversight because several theories propose that the transition to negative priming following a long duration prime reflects a decision strategy to compensate for the effect of increased perceptual fluency. In contrast, the nROUSE model of Huber and O'Reilly (2003) explains this transition as reflecting perceptual habituation, and thus a change to perceptual disfluency. We confirmed this prediction by applying a sequential sampling model (the diffusion race model) to accuracy and response time distributions from a new single item same-different version of the priming task. In this way, we measured strategic biases and perceptual fluency in each condition for each subject. The nROUSE model was only applied to accuracy from the original forced-choice version of the priming task. This application of nROUSE produced separate predictions for each subject regarding the degree of fluency and disfluency in each condition, and these predictions were confirmed by the drift rate parameters (i.e., fluency) from the response time model in contrast to the threshold parameters (i.e., bias). Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Frobenius and His Density Theorem for Primes

    Indian Academy of Sciences (India)

    coefficients of f modulo q. Then, the problem asks us to prove that there is some prime q for which f does not have a root in 71../ q7l... So, when is it true that an integral polynomial has roots in ... integral polynomial has a root in lL./qlL. for infinitely ..... part of town to the higher part, or buckets of cabbages. It is an elementary.

  20. Learning PrimeFaces extensions development

    CERN Document Server

    Jonna, Sudheer

    2014-01-01

    This book provides a step by step approach that explains the most important extension components and their features. All the major features are explained by using the JobHub application with supporting screenshots.If you are an intermediate to advanced level user (or developer) who already has a basic working knowledge of PrimeFaces, then this book is for you.The only thing you need to know is Java Server Faces(JSF).

  1. Priming effect on word reading and recall

    OpenAIRE

    Faria, Isabel Hub; Luegi, Paula

    2008-01-01

    This study focuses on priming as a function of exposure to bimodal stimuli of European Portuguese screen centred single words and isolated pictures inserted at the screen’s right upper corner, with four kinds of word-picture relation. The eye movements of 18 Portuguese native university students were registered while reading four sets of ten word-picture pairs, and their respective oral recall lists of words or pictures were kept. The results reveal a higher phonological primin...

  2. "Prime" Advertising Space: Measuring Implict Memory Online

    OpenAIRE

    Barratt, Madeleine

    2012-01-01

    In marketing literature, click-through-rates are generally employed to measure the success of banner advertisements online. This measure has led to the banner blindness hypothesis, which posits that internet users ignore banner advertisements. However, this measurement does not take into account the consumer action which may result from memory for advertised brands. This study illustrates that although there may not be explicit memory for these advertisements, consumers can be primed for adve...

  3. The Flavonoid Quercetin Ameliorates Liver Inflammation and Fibrosis by Regulating Hepatic Macrophages Activation and Polarization in Mice

    Directory of Open Access Journals (Sweden)

    Xi Li

    2018-02-01

    Full Text Available At present, there are no effective antifibrotic drugs for patients with chronic liver disease; hence, the development of antifibrotic therapies is urgently needed. Here, we performed an experimental and translational study to investigate the potential and underlying mechanism of quercetin treatment in liver fibrosis, mainly focusing on the impact of quercetin on macrophages activation and polarization. BALB/c mice were induced liver fibrosis by carbon tetrachloride (CCl4 for 8 weeks and concomitantly treated with quercetin (50 mg/kg or vehicle by daily gavage. Liver inflammation, fibrosis, and hepatic stellate cells (HSCs activation were examined. Moreover, massive macrophages accumulation, M1 macrophages and their related markers, such as tumor necrosis factor (TNF-α, interleukin (IL-1β, IL-6, and monocyte chemotactic protein-1 (MCP-1 in livers were analyzed. In vitro, we used Raw 264.7 cells to examine the effect of quercetin on M1-polarized macrophages activation. Our results showed that quercetin dramatically ameliorated liver inflammation, fibrosis, and inhibited HSCs activation. These results were attributed to the reductive recruitment of macrophages (F4/80+ and CD68+ into the liver in quercetin-treated fibrotic mice confirmed by immunostaining and expression levels of marker molecules. Importantly, quercetin strongly inhibited M1 polarization and M1-related inflammatory cytokines in fibrotic livers when compared with vehicle-treated mice. In vitro, studies further revealed that quercetin efficiently inhibited macrophages activation and M1 polarization, as well as decreased the mRNA expression of M1 macrophage markers such as TNF-α, IL-1β, IL-6, and nitric oxide synthase 2. Mechanistically, the inhibition of M1 macrophages by quercetin was associated with the decreased levels of Notch1 expression on macrophages both in vivo and in vitro. Taken together, our data indicated that quercetin attenuated CCl4-induced liver inflammation and

  4. The effect of unimodal affective priming on dichotic emotion recognition.

    Science.gov (United States)

    Voyer, Daniel; Myles, Daniel

    2017-11-15

    The present report concerns two experiments extending to unimodal priming the cross-modal priming effects observed with auditory emotions by Harding and Voyer [(2016). Laterality effects in cross-modal affective priming. Laterality: Asymmetries of Body, Brain and Cognition, 21, 585-605]. Experiment 1 used binaural targets to establish the presence of the priming effect and Experiment 2 used dichotically presented targets to examine auditory asymmetries. In Experiment 1, 82 university students completed a task in which binaural targets consisting of one of 4 English words inflected in one of 4 emotional tones were preceded by binaural primes consisting of one of 4 Mandarin words pronounced in the same (congruent) or different (incongruent) emotional tones. Trials where the prime emotion was congruent with the target emotion showed faster responses and higher accuracy in identifying the target emotion. In Experiment 2, 60 undergraduate students participated and the target was presented dichotically instead of binaurally. Primes congruent with the left ear produced a large left ear advantage, whereas right congruent primes produced a right ear advantage. These results indicate that unimodal priming produces stronger effects than those observed under cross-modal priming. The findings suggest that priming should likely be considered a strong top-down influence on laterality effects.

  5. Human development recruiting and selection

    Directory of Open Access Journals (Sweden)

    Maksimović Marijana

    2002-01-01

    Full Text Available Along with the development of trends towards internationalization and globalization, human resource management and, especially, international human resource management, attracted overall theoretical and practical interest. International environment is complex, made of numerous elements like social organization, laws, education, values and attitudes, religion language, politics, material and technological culture. In multicultural environment, strategic activities could be multiplied through economical political, cultural, social and technological spheres of action, making the recruitment, selection and successful resource allocation in the international human resource management a real challenge for top management. In international human resource management practice, several approaches to the recruitment have differentiated, playing the key roles in hiring talented individuals and retaining efficient workforce KW resources, labor force, recruiting, managers, education

  6. Uncover the recruiter in you!

    CERN Multimedia

    2013-01-01

    2013 saw the launch of the one-day training course "Selecting the best person for CERN". So far, 10 courses have taken place and over 100 participants have taken part in this interactive, hands on experience.   The course has been met with much enthusiasm and positive feedback, with participants not only feeling better prepared and organised for the recruitment boards, but also equipped with concrete tools on how to prepare and conduct an effective selection interview. Following on from this success, further sessions are planned in 2014: we look forward to welcoming recruiting supervisors and board members who are likely to take part in a recruitment process, whether for LD or LD2IC, and who are interested in finding out more about how to get the most out of this important process! To enrol to this course, please follow this link: "Selecting the best person for CERN".

  7. Microvascular Recruitment in Insulin Resistance

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker

    the resonating sound from the microbubbles in the systemic circulation were recorded for determination of microvascular recruitment in designated muscle segments. Results showed that microvascular recruitment increased with insulin stimulation by ~30% in rats and ~40% in humans (study I). Furthermore......, it was observed that muscle contractions increased muscle perfusion rapidly by 3-4 fold and by 1-2 fold compared to basal and insulin, respectively, in both rat and human skeletal muscle (study I). The real-time contrast-enhanced ultrasound method was applied to investigate the vaso-active effect of the incretin...... hormone glucagon-like-peptide-1 (GLP-1) in the microcirculation. Glucagon-like-peptide-1 analogs are drugs used for treatments of insulin resistance and type 2 diabetes but the vascular effects of GLP-1 in vivo are elusive. Here it was shown that GLP-1 rapidly increased the microvascular recruitment...

  8. The frequency attenuation effect in identity and associative priming.

    Science.gov (United States)

    Nievas, Francisco

    2010-05-01

    Three lexical decision experiments were carried out, where the masked priming paradigm is used to study the role of the frequency attenuation effect (more priming in low-frequency target words than in high-frequency target words) in repetition and associative priming, manipulating Prime Duration (PD) and Stimulus Onset Asynchrony (SOA). A new concept was introduced, Minimum Time Threshold (MTT), this is, the minimum time interval of exposure to the masked word in order to become aware of it. Results support the notion that MTT is a key to the appearance of the frequency attenuation effect when enough word processing time is allowed. Results do not support the unified explanation of masked priming and long-term priming as proposed by Bodner and Masson (2001). Moreover, information feedback from the semantic level was not the reason for the frequency attenuation effect in repetition priming.

  9. Campus Recruiting: What the Recruiters Are Looking For.

    Science.gov (United States)

    Turner, Martha R.; And Others

    1996-01-01

    A survey of 111 campus recruiters of graduating students shows agreement that interviews are the most important selection method. Students' verbal communication skills, character, work experience, and academic performance were judged the most important personal characteristics in applicants. Work-related expectations and attitudes were the most…

  10. Do recruitment ties affect wages?

    DEFF Research Database (Denmark)

    Larsen, Anna Folke; Rand, John; Torm, Nina Elisabeth

    This paper examines the extent to which recruitment ties affect individual wage outcomes in small and medium scale manufacturing firms. Based on a unique matched employer-employee dataset from Vietnam we find that there is a significant positive wage premium associated with obtaining a job through...... an informal contact, when controlling for standard determinants of wage compensation. Moreover, we show that the mechanism through which informal contacts affect wages depends on the type of recruitment tie used. The findings are robust across location, firm size categories and different worker types....

  11. Random reward priming is task-contingent: The robustness of the 1-trial reward priming effect

    Directory of Open Access Journals (Sweden)

    Árni Gunnar Ásgeirsson

    2014-04-01

    Full Text Available Consistent financial reward of particular features influences the allocation of visual attention in many ways. More surprising are 1-trial reward priming effects on attention where reward schedules are random and reward on one trial influences attentional allocation on the next. Those findings are thought to reflect that rewarded features become more salient than unrewarded ones on the subsequent trial. Here we attempt to conceptually replicate this effect, testing its generalizability. In three versions of an analogous paradigm to the additional singleton paradigm involving singleton search for a Gabor patch of odd spatial frequency we found no evidence of reward priming, while we only partially replicate the reward priming in the exact original paradigm tested by Hickey and colleagues. The results cast doubt on the proposal that random reward enhances salience, suggested in the original papers, and highlight the need for a more nuanced account. In many other paradigms reward effects have been found to progress gradually, becoming stronger as they build up, and we argue that for robust reward priming, reward schedules need to be more consistent than in the original 1-trial reward priming paradigm.

  12. A Strategic Systems Model for Effective Recruiting

    National Research Council Canada - National Science Library

    Woolever, Daniel

    2003-01-01

    .... After introducing a model for effective and efficient recruiting, this Strategic Research Project describes the Air Force recruiting organizational structure, management processes and practices...

  13. DMPD: Nuclear receptors in macrophages: a link between metabolism and inflammation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18022390 Nuclear receptors in macrophages: a link between metabolism and inflammati...on. Szanto A, Roszer T. FEBS Lett. 2008 Jan 9;582(1):106-16. Epub 2007 Nov 20. (.png) (.svg) (.html) (.csml) Show Nuclear... receptors in macrophages: a link between metabolism and inflammation. PubmedID 18022390 Title Nuclear

  14. DMPD: Receptor tyrosine kinases and the regulation of macrophage activation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14726496 Receptor tyrosine kinases and the regulation of macrophage activation. Cor...osine kinases and the regulation of macrophage activation. PubmedID 14726496 Title Receptor tyrosine...rell PH, Morrison AC, Lutz MA. J Leukoc Biol. 2004 May;75(5):731-7. Epub 2004 Jan 14. (.png) (.svg) (.html) (.csml) Show Receptor tyr

  15. Colonic macrophage polarization in homeostasis, inflammation, and cancer

    Science.gov (United States)

    Appleyard, Caroline B.

    2016-01-01

    Our review focuses on the colonic macrophage, a monocyte-derived, tissue-resident macrophage, and the role it plays in health and disease, specifically in inflammatory conditions such as inflammatory bowel disease and cancer of the colon and rectum. We give special emphasis to macrophage polarization, or phenotype, in these different states. We focus on macrophages because they are one of the most numerous leukocytes in the colon, and because they normally contribute to homeostasis through an anti-inflammatory phenotype. However, in conditions such as inflammatory bowel disease, proinflammatory macrophages are increased in the colon and have been linked to disease severity and progression. In colorectal cancer, tumor cells may employ anti-inflammatory macrophages to promote tumor growth and dissemination, whereas proinflammatory macrophages may antagonize tumor growth. Given the key roles that this cell type plays in homeostasis, inflammation, and cancer, the colonic macrophage is an intriguing therapeutic target. As such, potential macrophage-targeting strategies are discussed. PMID:27229123

  16. Transplantation of neuronal-primed human bone marrow mesenchymal stem cells in hemiparkinsonian rodents.

    Directory of Open Access Journals (Sweden)

    Melissa L M Khoo

    Full Text Available Bone marrow-derived human mesenchymal stem cells (hMSCs have shown promise in in vitro neuronal differentiation and in cellular therapy for neurodegenerative disorders, including Parkinson' disease. However, the effects of intracerebral transplantation are not well defined, and studies do not agreed on the optimal neuronal differentiation method. Here, we investigated three growth factor-based neuronal differentiation procedures (using FGF-2/EGF/PDGF/SHH/FGF-8/GDNF, and found all to be capable of eliciting an immature neural phenotype, in terms of cell morphology and gene/protein expression. The neuronal-priming (FGF-2/EGF method induced neurosphere-like formation and the highest NES and NR4A2 expression by hMSCs. Transplantation of undifferentiated and neuronal-primed hMSCs into the striatum and substantia nigra of 6-OHDA-lesioned hemiparkinsonian rats revealed transient graft survival of 7 days, despite the reported immunosuppressive properties of MSCs and cyclosporine-immunosuppression of rats. Neither differentiation of hMSCs nor induction of host neurogenesis was observed at injection sites, and hMSCs continued producing mesodermal fibronectin. Strategies for improving engraftment and differentiation post-transplantation, such as prior in vitro neuronal-priming, nigral and striatal grafting, and co-transplantation of olfactory ensheathing cells that promote neural regeneration, were unable to provide advantages. Innate inflammatory responses (Iba-1-positive microglia/macrophage and GFAP-positive astrocyte activation and accumulation were detected around grafts within 7 days. Our findings indicate that growth factor-based methods allow hMSC differentiation toward immature neuronal-like cells, and contrary to previous reports, only transient survival and engraftment of hMSCs occurs following transplantation in immunosuppressed hemiparkinsonian rats. In addition, suppression of host innate inflammatory responses may be a key factor for

  17. Nogo-B Facilitates LPS-Mediated Immune Responses by Up-Regulation of TLR4-Signaling in Macrophage RAW264.7

    Directory of Open Access Journals (Sweden)

    Ying Zhu

    2017-01-01

    Full Text Available Background/Aims: Nogo-B, a member of the reticulon family of proteins, is mainly located in the endoplasmic reticulum (ER. Here, we investigate the function and mechanism of Nogo-B in the regulation of TLR4-associated immune responses in the macrophage cell line of RAW264.7. Methods: Nogo-B was up- and down-regulated through the use of appropriate adenoviral vectors or siRNA, and the effects of Nogo-B on macrophages under liposaccharide (LPS stimulation were evaluated via western blotting, immunofluorescence, enzyme-linked immunosorbent assay (ELISA, flow cytometric analysis, and transwell assay. Results: Our data indicates that the protein of Nogo-B was down-regulated in a time- and dose-dependent manner following LPS administration in the macrophage. Nogo-B overexpression increased the production of inflammatory cytokines (MCP-1, TNF-α, IL-1β, and TGF-β, enhanced macrophage migration activities, activated major histocompatibility complex II (MHC II, and elevated the expression of macrophage scavenger receptor 1(MSR1, all of which suggest that Nogo-B is necessary for immune responses and plays an important role in regulating macrophage recruitment. Mechanistically, Nogo-B may enhance TLR4 expression in macrophage surfaces, activate mitogen-activated protein kinase (MAPK pathways, and initiate inflammatory responses. Conclusion: These findings illustrate the key regulatory functions of Nogo-B in facilitating LPS-mediated immune responses through promoting the phosphorylation of MAP kinase.

  18. Regulation of alternative macrophage activation in the liver following acetaminophen intoxication by stem cell-derived tyrosine kinase

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, Carol R., E-mail: cgardner@pharmacy.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ 08854 (United States); Hankey, Pamela [Department of Veterinary and Biomedical Science, Pennsylvania State University, University Park, PA 16802 (United States); Mishin, Vladimir; Francis, Mary [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ 08854 (United States); Yu, Shan [Department of Veterinary and Biomedical Science, Pennsylvania State University, University Park, PA 16802 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854 (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ 08854 (United States)

    2012-07-15

    Stem cell-derived tyrosine kinase (STK) is a transmembrane receptor reported to play a role in macrophage switching from a classically activated/proinflammatory phenotype to an alternatively activated/wound repair phenotype. In the present studies, STK{sup −/−} mice were used to assess the role of STK in acetaminophen-induced hepatotoxicity as evidence suggests that the pathogenic process involves both of these macrophage subpopulations. In wild type mice, centrilobular hepatic necrosis and increases in serum transaminase levels were observed within 6 h of acetaminophen administration (300 mg/kg, i.p.). Loss of STK resulted in a significant increase in sensitivity of mice to the hepatotoxic effects of acetaminophen and increased mortality, effects independent of its metabolism. This was associated with reduced levels of hepatic glutathione, rapid upregulation of inducible nitric oxide synthase, and prolonged induction of heme oxygenase-1, suggesting excessive oxidative stress in STK{sup −/−} mice. F4/80, a marker of mature macrophages, was highly expressed on subpopulations of Kupffer cells in livers of wild type, but not STK{sup −/−} mice. Whereas F4/80{sup +} macrophages rapidly declined in the livers of wild type mice following acetaminophen intoxication, they increased in STK{sup −/−} mice. In wild type mice hepatic expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-12, products of classically activated macrophages, increased after acetaminophen administration. Monocyte chemotactic protein-1 (MCP-1) and its receptor, CCR2, as well as IL-10, mediators involved in recruiting and activating anti-inflammatory/wound repair macrophages, also increased in wild type mice after acetaminophen. Loss of STK blunted the effects of acetaminophen on expression of TNFα, IL-1β, IL-12, MCP-1 and CCR2, while expression of IL-10 increased. Hepatic expression of CX3CL1, and its receptor, CX3CR1 also increased in STK{sup −/−} mice

  19. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Directory of Open Access Journals (Sweden)

    Mário Henrique M Barros

    Full Text Available Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a

  20. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Science.gov (United States)

    Barros, Mário Henrique M; Hauck, Franziska; Dreyer, Johannes H; Kempkes, Bettina; Niedobitek, Gerald

    2013-01-01

    Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool for

  1. BMP pathway regulation of and by macrophages.

    Directory of Open Access Journals (Sweden)

    Megha Talati

    Full Text Available Pulmonary arterial hypertension (PAH is a disease of progressively increasing pulmonary vascular resistance, associated with mutations of the type 2 receptor for the BMP pathway, BMPR2. The canonical signaling pathway for BMPR2 is through the SMAD family of transcription factors. BMPR2 is expressed in every cell type, but the impact of BMPR2 mutations affecting SMAD signaling, such as Bmpr2delx4+, had only previously been investigated in smooth muscle and endothelium. In the present study, we created a mouse with universal doxycycline-inducible expression of Bmpr2delx4+ in order to determine if broader expression had an impact relevant to the development of PAH. We found that the most obvious phenotype was a dramatic, but patchy, increase in pulmonary inflammation. We crossed these double transgenic mice onto an NF-κB reporter strain, and by luciferase assays on live mice, individual organs and isolated macrophages, we narrowed down the origin of the inflammatory phenotype to constitutive activation of tissue macrophages. Study of bone marrow-derived macrophages from mutant and wild-type mice suggested a baseline difference in differentiation state in Bmpr2 mutants. When activated with LPS, both mutant and wild-type macrophages secrete BMP pathway inhibitors sufficient to suppress BMP pathway activity in smooth muscle cells (SMC treated with conditioned media. Functionally, co-culture with macrophages results in a BMP signaling-dependent increase in scratch closure in cultured SMC. We conclude that SMAD signaling through BMP is responsible, in part, for preventing macrophage activation in both live animals and in cells in culture, and that activated macrophages secrete BMP inhibitors in sufficient quantity to cause paracrine effect on vascular smooth muscle.

  2. Mechanisms of masked evaluative priming: task sets modulate behavioral and electrophysiological priming for picture and words differentially.

    Science.gov (United States)

    Kiefer, Markus; Liegel, Nathalie; Zovko, Monika; Wentura, Dirk

    2017-04-01

    Research with the evaluative priming paradigm has shown that affective evaluation processes reliably influence cognition and behavior, even when triggered outside awareness. However, the precise mechanisms underlying such subliminal evaluative priming effects, response activation vs semantic processing, are matter of a debate. In this study, we determined the relative contribution of semantic processing and response activation to masked evaluative priming with pictures and words. To this end, we investigated the modulation of masked pictorial vs verbal priming by previously activated perceptual vs semantic task sets and assessed the electrophysiological correlates of priming using event-related potential (ERP) recordings. Behavioral and electrophysiological effects showed a differential modulation of pictorial and verbal subliminal priming by previously activated task sets: Pictorial priming was only observed during the perceptual but not during the semantic task set. Verbal priming, in contrast, was found when either task set was activated. Furthermore, only verbal priming was associated with a modulation of the N400 ERP component, an index of semantic processing, whereas a priming-related modulation of earlier ERPs, indexing visuo-motor S-R activation, was found for both picture and words. The results thus demonstrate that different neuro-cognitive processes contribute to unconscious evaluative priming depending on the stimulus format. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  3. A macrophage activation switch (MAcS)-index for assessment of monocyte/macrophage activation

    DEFF Research Database (Denmark)

    Maniecki, Maciej Bogdan; Lauridsen, Mette; Knudsen, Troels Bygum

    2008-01-01

    , simplified by the M1-M2 dichotomy of classically activated (M1), pro-inflammatory cells and alternatively activated (M2), anti-inflammatory cells. Macrophages, however, display a large degree of flexibility and are able to switch between activation states (1). The hemoglobin scavenger receptor CD163...... is expressed exclusively on monocytes and macrophages, and its expression is strongly induced by anti-inflammatory stimuli like IL10 and glucocorticoid, making CD163 an ideal M2 macrophage marker (2). Furthermore a soluble variant of CD163 (sCD163) is shed from the cell surface to plasma by protease mediated.......058-5139) (panti-inflammatory state.   CONCLUSION: We present a CD163-derived macrophage activation switch (MAcS)-index, which seems able to differentiate between (predominantly) pro-inflammatory and anti-inflammatory macrophage activation. The index needs...

  4. LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature.

    Science.gov (United States)

    van der Does, Anne M; Beekhuizen, Henry; Ravensbergen, Bep; Vos, Tim; Ottenhoff, Tom H M; van Dissel, Jaap T; Drijfhout, Jan W; Hiemstra, Pieter S; Nibbering, Peter H

    2010-08-01

    The human cathelicidin LL-37 has broad-spectrum antimicrobial activity. It also participates at the interface of innate and adaptive immunity by chemoattracting immune effector cells, modulating the production of a variety of inflammatory mediators by different cell types, and regulating the differentiation of monocytes into dendritic cells. In this study, we investigated the effects of LL-37 on the differentiation of human monocytes into anti-inflammatory macrophages (MPhi-2; driven by M-CSF) versus proinflammatory macrophages (MPhi-1; driven by GM-CSF) as well as on fully differentiated MPhi-1 and MPhi-2. Results revealed that monocytes cultured with M-CSF in the presence of LL-37 resulted in macrophages displaying a proinflammatory signature, namely, low expression of CD163 and little IL-10 and profound IL-12p40 production on LPS stimulation. The effects of LL-37 on M-CSF-driven macrophage differentiation were dose- and time-dependent with maximal effects observed at 10 microg/ml when the peptide was present from the start of the cultures. The peptide enhanced the GM-CSF-driven macrophage differentiation. Exposure of fully differentiated MPhi-2 to LL-37 for 6 d resulted in macrophages that produced less IL-10 and more IL-12p40 on LPS stimulation than control MPhi-2. In contrast, LL-37 had no effect on fully differentiated MPhi-1. Peptide mapping using a set of 16 overlapping 22-mer peptides covering the complete LL-37 sequence revealed that the C-terminal portion of LL-37 is responsible for directing macrophage differentiation. Our results furthermore indicate that the effects of LL-37 on macrophage differentiation required internalization of the peptide. Together, we conclude that LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature.

  5. A Blueprint for Student Recruitment

    Science.gov (United States)

    Chamberlain, Frank M.

    1977-01-01

    A marketing plan from the Young Presidents' Organization Task Force is offered: define the market; identify the target student; clarify the college selection process; assess the competition; define the college in terms of market needs; develop a recruiting strategy; develop objectives for the year; spell out the tactics; and manage for results.…

  6. Recruiting Teachers--Future Prospects.

    Science.gov (United States)

    Schlechty, Phillip C.; Joslin, Anne W.

    1984-01-01

    Comprehensive reform in the ways teachers are recruited, trained, evaluated, and rewarded is required if the status of the teaching profession and the present quality of education is to be improved. A new career structure, simplification of certification, and reconceptualization of the teaching role are possible remedies. (KH)

  7. Recruiting physicians without inviting trouble.

    Science.gov (United States)

    Hoch, L J

    1989-05-01

    Many hospitals use physician recruitment strategies--generally assistance or employment strategies--to ensure medical staff loyalty. Although these strategies appeal to both hospitals and physicians, they are becoming increasingly problematic. Over the past three years, the government has issued pronouncements that question their legality. Thus any hospital considering physician recruitment strategies would be wise to evaluate them in light of various legal issues. such as reimbursement, nonprofit taxation, corporate practice of medicine, and certificate-of-need statutes. The consequences of failing to consider these issues can be ominous. The penalties for violating the proscribed remuneration provision of the Medicare act can include a fine, imprisonment, suspension from the Medicare and Medicaid programs, or loss of license. Payment issues can result in reduced reimbursement levels. Nonprofit taxation issues can trigger the loss of tax exemption. As a result of the corporate practice of medicine, a physician recruitment strategy may not be reimbursable by third-party payers or may even constitute the unauthorized practice of medicine. Finally, in some states, physician recruitment may trigger certificate-of-need review.

  8. Recruiting Trends, 2007-2008

    Science.gov (United States)

    Collegiate Employment Research Institute (NJ3), 2008

    2008-01-01

    This paper presents the recruiting trends for 2007-2008. This year's report is based on 994 respondents, including 84 K-12 school districts. The researchers focused attention on growing companies, based on lists from Forbes and Inc. magazines, and as a result, they have more small and medium-size employers represented this year. The sample…

  9. Recruiting Strategies for Women's Colleges.

    Science.gov (United States)

    Ricci, Ronald J.

    1994-01-01

    Methods for combating declining applicant pools at women's colleges are discussed. Research suggests that effective student recruitment can be facilitated by the use of single-gender market niche as a means for differentiation and parent influence for promotion. Review of strategies currently used indicate these marketing methods are underused and…

  10. Transposed-letter priming of prelexical orthographic representations.

    Science.gov (United States)

    Kinoshita, Sachiko; Norris, Dennis

    2009-01-01

    A prime generated by transposing two internal letters (e.g., jugde) produces strong priming of the original word (judge). In lexical decision, this transposed-letter (TL) priming effect is generally weak or absent for nonword targets; thus, it is unclear whether the origin of this effect is lexical or prelexical. The authors describe the Bayesian Reader theory of masked priming (D. Norris & S. Kinoshita, 2008), which explains why nonwords do not show priming in lexical decision but why they do in the cross-case same-different task. This analysis is followed by 3 experiments that show that priming in this task is not based on low-level perceptual similarity between the prime and target, or on phonology, to make the case that priming is based on prelexical orthographic representation. The authors then use this task to demonstrate equivalent TL priming effects for nonwords and words. The results are interpreted as the first reliable evidence based on the masked priming procedure that letter position is not coded absolutely within the prelexical, orthographic representation. The implications of the results for current letter position coding schemes are discussed.

  11. Wheat seed enhancement by vitamin and hormonal priming

    International Nuclear Information System (INIS)

    Khan, M.B.; Gurchani, M.A.; Hussain, M.

    2011-01-01

    Seed priming has proven beneficial in many important agricultural crops. The present study was conducted to explore the role (if any) of hormonal and vitamin seed priming to improve the germination, seedling emergence, early seedling establishment, electrolyte leakage and nutrients uptake in wheat seedlings. The wheat seeds were soaked for 48 hours in aerated solution of salicylic acid, ascorbic acid, kinetin and GA3 with 20 ppm concentration of each solution, whereas untreated seeds were taken as control. Seed priming with ascorbic acid resulted in maximum final germination and emergence percentage (FGP and FEP), radical and plumule length, root and shoot length, number of secondary roots, root shoot ratio, root dry weight, shoot dry weight and seedling dry weight compared to control (untreated seeds). Minimum mean germination and emergence time (MGT and MET) was recorded in seeds primed with kinetin and GA3. While in case of biochemical attributes, seedling potassium contents were decreased by hormonal seed priming while total soluble sugars were increased by salicylic acid and ascorbic acid seed priming. Hormonal seed priming had non-significant effect on phosphorus seedling contents. Untreated (Control) seeds showed maximum electrical conductivity at 0.5, 1, 2, 6, 12 and 24 h after inbibition than primed seeds against the minimum electrical conductivity that was recorded in seeds primed with salicylic acid and ascorbic acid. In conclusion, the wheat seeds primed with 20 ppm solution of ascorbic acid may be used for wheat seed invigoration. (author)

  12. Intramacrophage survival of uropathogenic Escherichia coli: Differences between diverse clinical isolates and between mouse and human macrophages

    KAUST Repository

    Bokil, Nilesh J.

    2011-11-01

    Uropathogenic E. coli (UPEC) are the primary cause of urinary tract infections. Recent studies have demonstrated that UPEC can invade and replicate within epithelial cells, suggesting that this bacterial pathogen may occupy an intracellular niche within the host. Given that many intracellular pathogens target macrophages, we assessed the interactions between UPEC and macrophages. Colonization of the mouse bladder by UPEC strain CFT073 resulted in increased expression of myeloid-restricted genes, consistent with the recruitment of inflammatory macrophages to the site of infection. In in vitro assays, CFT073 was able to survive within primary mouse bone marrow-derived macrophages (BMM) up to 24h post-infection. Three additional well-characterized clinical UPEC isolates associated with distinct UTI symptomatologies displayed variable long-term survival within BMM. UPEC strains UTI89 and VR50, originally isolated from patients with cystitis and asymptomatic bacteriuria respectively, showed elevated bacterial loads in BMM at 24h post-infection as compared to CFT073 and the asymptomatic bacteriuria strain 83972. These differences did not correlate with differential effects on macrophage survival or initial uptake of bacteria. E. coli UTI89 localized to a Lamp1 + vesicular compartment within BMM. In contrast to survival within mouse BMM, intracellular bacterial loads of VR50 were low in both human monocyte-derived macrophages (HMDM) and in human T24 bladder epithelial cells. Collectively, these data suggest that some UPEC isolates may subvert macrophage anti-microbial pathways, and that host species differences may impact on intracellular UPEC survival. © 2011 Elsevier GmbH.

  13. Playing hide-and-seek with host macrophages through the use of mycobacterial cell envelope phthiocerol dimycocerosates and phenolic glycolipids

    Directory of Open Access Journals (Sweden)

    Ainhoa eARBUES

    2014-12-01

    Full Text Available Mycobacterial pathogens, including Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB, have evolved a remarkable ability to evade the immune system in order to survive and to colonize the host. Among the most important evasion strategies is the capacity of these bacilli to parasitize host macrophages, since these are major effector cells against intracellular pathogens that can be used as long-term cellular reservoirs. Mycobacterial pathogens employ an array of virulence factors that manipulate macrophage function to survive and establish infection. Until recently, however, the role of mycobacterial cell envelope lipids as virulence factors in macrophage subversion has remained elusive. Here, we will address exclusively the proposed role for phthiocerol dimycocerosates (DIM in the modulation of the resident macrophage response and that of phenolic glycolipids (PGL in the regulation of the recruitment and phenotype of incoming macrophage precursors to the site of infection. We will provide a unique perspective of potential additional functions for these lipids, and highlight obstacles and opportunities to further understand their role in the pathogenesis of TB and other mycobacterial diseases.

  14. Adipocyte-Macrophage Cross-Talk in Obesity.

    Science.gov (United States)

    Engin, Ayse Basak

    2017-01-01

    Obesity is characterized by the chronic low-grade activation of the innate immune system. In this respect, macrophage-elicited metabolic inflammation and adipocyte-macrophage interaction has a primary importance in obesity. Large amounts of macrophages are accumulated by different mechanisms in obese adipose tissue. Hypertrophic adipocyte-derived chemotactic monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2) pathway also promotes more macrophage accumulation into the obese adipose tissue. However, increased local extracellular lipid concentrations is a final mechanism for adipose tissue macrophage accumulation. A paracrine loop involving free fatty acids and tumor necrosis factor-alpha (TNF-alpha) between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes in the adipose tissue. Adipocyte-specific caspase-1 and production of interleukin-1beta (IL-1beta) by macrophages; both adipocyte and macrophage induction by toll like receptor-4 (TLR4) through nuclear factor-kappaB (NF-kappaB) activation; free fatty acid-induced and TLR-mediated activation of c-Jun N-terminal kinase (JNK)-related pro-inflammatory pathways in CD11c+ immune cells; are effective in macrophage accumulation and in the development of adipose tissue inflammation. Old adipocytes are removed by macrophages through trogocytosis or sending an "eat me" signal. The obesity-induced changes in adipose tissue macrophage numbers are mainly due to increases in the triple-positive CD11b+ F4/80+ CD11c+ adipose tissue macrophage subpopulation. The ratio of M1-to-M2 macrophages is increased in obesity. Furthermore, hypoxia along with higher concentrations of free fatty acids exacerbates macrophage-mediated inflammation in obesity. The metabolic status of adipocytes is a major determinant of macrophage inflammatory output. Macrophage/adipocyte fatty-acid-binding proteins act at the interface of metabolic and inflammatory pathways. Both macrophages and

  15. Investigating the Role of TNF-α and IFN-γ Activation on the Dynamics of iNOS Gene Expression in LPS Stimulated Macrophages.

    Directory of Open Access Journals (Sweden)

    Taha Salim

    Full Text Available Macrophage produced inducible nitric oxide synthase (iNOS is known to play a critical role in the proinflammatory response against intracellular pathogens by promoting the generation of bactericidal reactive nitrogen species. Robust and timely production of nitric oxide (NO by iNOS and analogous production of reactive oxygen species are critical components of an effective immune response. In addition to pathogen associated lipopolysaccharides (LPS, iNOS gene expression is dependent on numerous proinflammatory cytokines in the cellular microenvironment of the macrophage, two of which include interferon gamma (IFN-γ and tumor necrosis factor alpha (TNF-α. To understand the synergistic effect of IFN-γ and TNF-α activation, and LPS stimulation on iNOS expression dynamics and NO production, we developed a systems biology based mathematical model. Using our model, we investigated the impact of pre-infection cytokine exposure, or priming, on the system. We explored the essentiality of IFN-γ priming to the robustness of initial proinflammatory response with respect to the ability of macrophages to produce reactive species needed for pathogen clearance. Results from our theoretical studies indicated that IFN-γ and subsequent activation of IRF1 are essential in consequential production of iNOS upon LPS stimulation. We showed that IFN-γ priming at low concentrations greatly increases the effector response of macrophages against intracellular pathogens. Ultimately the model demonstrated that although TNF-α contributed towards a more rapid response time, measured as time to reach maximum iNOS production, IFN-γ stimulation was significantly more significant in terms of the maximum expression of iNOS and the concentration of NO produced.

  16. Investigating the Role of TNF-α and IFN-γ Activation on the Dynamics of iNOS Gene Expression in LPS Stimulated Macrophages.

    Science.gov (United States)

    Salim, Taha; Sershen, Cheryl L; May, Elebeoba E

    2016-01-01

    Macrophage produced inducible nitric oxide synthase (iNOS) is known to play a critical role in the proinflammatory response against intracellular pathogens by promoting the generation of bactericidal reactive nitrogen species. Robust and timely production of nitric oxide (NO) by iNOS and analogous production of reactive oxygen species are critical components of an effective immune response. In addition to pathogen associated lipopolysaccharides (LPS), iNOS gene expression is dependent on numerous proinflammatory cytokines in the cellular microenvironment of the macrophage, two of which include interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). To understand the synergistic effect of IFN-γ and TNF-α activation, and LPS stimulation on iNOS expression dynamics and NO production, we developed a systems biology based mathematical model. Using our model, we investigated the impact of pre-infection cytokine exposure, or priming, on the system. We explored the essentiality of IFN-γ priming to the robustness of initial proinflammatory response with respect to the ability of macrophages to produce reactive species needed for pathogen clearance. Results from our theoretical studies indicated that IFN-γ and subsequent activation of IRF1 are essential in consequential production of iNOS upon LPS stimulation. We showed that IFN-γ priming at low concentrations greatly increases the effector response of macrophages against intracellular pathogens. Ultimately the model demonstrated that although TNF-α contributed towards a more rapid response time, measured as time to reach maximum iNOS production, IFN-γ stimulation was significantly more significant in terms of the maximum expression of iNOS and the concentration of NO produced.

  17. 28 CFR 54.510 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Recruitment. 54.510 Section 54.510... in Employment in Education Programs or Activities Prohibited § 54.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment...

  18. 44 CFR 19.310 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Recruitment. 19.310 Section... RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 19.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 19.300 through 19...

  19. 15 CFR 8a.510 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Recruitment. 8a.510 Section 8a.510... in Employment in Education Programs or Activities Prohibited § 8a.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment...

  20. 7 CFR 15a.53 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Recruitment. 15a.53 Section 15a.53 Agriculture Office... Activities Prohibited § 15a.53 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has...

  1. 31 CFR 28.510 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Recruitment. 28.510 Section 28.510... Basis of Sex in Employment in Education Programs or Activities Prohibited § 28.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment...

  2. 34 CFR 106.53 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Recruitment. 106.53 Section 106.53 Education... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be presently...

  3. 36 CFR 1211.510 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Recruitment. 1211.510 Section... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be presently...

  4. 18 CFR 1317.510 - Recruitment.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Recruitment. 1317.510... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be presently...

  5. 10 CFR 5.310 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Recruitment. 5.310 Section 5.310 Energy NUCLEAR REGULATORY... FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 5.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 5.300 through 5.310 apply shall not...

  6. 7 CFR 15a.23 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Recruitment. 15a.23 Section 15a.23 Agriculture Office... FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 15a.23 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which this subpart applies shall...

  7. 22 CFR 229.510 - Recruitment.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Recruitment. 229.510 Section 229.510 Foreign... in Education Programs or Activities Prohibited § 229.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring...

  8. 20 CFR 655.30 - Supervised recruitment.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Supervised recruitment. 655.30 Section 655.30... Workers) § 655.30 Supervised recruitment. (a) Supervised recruitment. Where an employer is found to have... failed to adequately conduct recruitment activities or failed in any obligation of this part, the CO may...

  9. 22 CFR 146.510 - Recruitment.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Recruitment. 146.510 Section 146.510 Foreign... Education Programs or Activities Prohibited § 146.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees...

  10. 20 CFR 656.21 - Supervised recruitment.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Supervised recruitment. 656.21 Section 656.21... Supervised recruitment. (a) Supervised recruitment. Where the Certifying Officer determines it appropriate, post-filing supervised recruitment may be required of the employer for the pending application or...

  11. 41 CFR 101-4.510 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Recruitment. 101-4.510... Employment in Education Programs or Activities Prohibited § 101-4.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring...

  12. 45 CFR 83.12 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Recruitment. 83.12 Section 83.12 Public Welfare... § 83.12 Recruitment. (a) Comparable recruitment. A federally supported entity shall, with respect to... demonstrate that such action is part of a recruitment program which does not have the effect of discriminating...

  13. 13 CFR 113.510 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Recruitment. 113.510 Section 113... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be presently...

  14. 14 CFR 1253.510 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Recruitment. 1253.510 Section 1253.510... in Employment in Education Programs or Activities Prohibited § 1253.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment...

  15. 45 CFR 618.510 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Recruitment. 618.510 Section 618.510 Public... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be presently...

  16. 45 CFR 2555.310 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recruitment. 2555.310 Section 2555.310 Public... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 2555.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 2555.300 through 2555.310 apply shall not discriminate on the...

  17. 45 CFR 618.310 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Recruitment. 618.310 Section 618.310 Public... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 618.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 618.300 through 618.310 apply shall not discriminate on the...

  18. 43 CFR 41.510 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Recruitment. 41.510 Section 41.510 Public... in Employment in Education Programs or Activities Prohibited § 41.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment...

  19. 13 CFR 113.310 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Recruitment. 113.310 Section 113... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 113.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 113.300 through 113.310 apply shall not discriminate on the...

  20. 45 CFR 86.53 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Recruitment. 86.53 Section 86.53 Public Welfare... in Employment in Education Programs or Activities Prohibited § 86.53 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment...

  1. 31 CFR 28.310 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Recruitment. 28.310 Section 28.310... Basis of Sex in Admission and Recruitment Prohibited § 28.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 28.300 through 28.310 apply shall not discriminate on the basis of sex in...

  2. 49 CFR 25.510 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Recruitment. 25.510 Section 25.510 Transportation... Education Programs or Activities Prohibited § 25.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees...

  3. 36 CFR 1211.310 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Recruitment. 1211.310 Section... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 1211.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 1211.300 through 1211.310 apply shall not discriminate on the...

  4. 40 CFR 5.510 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Recruitment. 5.510 Section 5.510... in Employment in Education Programs or Activities Prohibited § 5.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment...

  5. 45 CFR 2555.510 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recruitment. 2555.510 Section 2555.510 Public... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be presently...

  6. 32 CFR 196.310 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Recruitment. 196.310 Section 196.310 National... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 196.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 196.300 through 196.310 apply shall not discriminate on the...

  7. 38 CFR 23.510 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Recruitment. 23.510... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be presently...

  8. 32 CFR 196.510 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Recruitment. 196.510 Section 196.510 National... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be presently...

  9. 6 CFR 17.510 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Recruitment. 17.510 Section 17.510 Domestic... in Employment in Education Programs or Activities Prohibited § 17.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment...

  10. 29 CFR 36.510 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Recruitment. 36.510 Section 36.510 Labor Office of the... Activities Prohibited § 36.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has...

  11. 18 CFR 1317.310 - Recruitment.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Recruitment. 1317.310... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 1317.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 1317.300 through 1317.310 apply shall not discriminate on the...

  12. 24 CFR 3.310 - Recruitment.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Recruitment. 3.310 Section 3.310... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 3.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 3.300 through 3.310 apply shall not discriminate on the basis...

  13. 38 CFR 23.310 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Recruitment. 23.310... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 23.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 23.300 through 23.310 apply shall not discriminate on the...

  14. 44 CFR 19.510 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Recruitment. 19.510 Section... Programs or Activities Prohibited § 19.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a...

  15. 34 CFR 106.23 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Recruitment. 106.23 Section 106.23 Education... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 106.23 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which this subpart applies shall not discriminate on the basis of sex...

  16. 24 CFR 3.510 - Recruitment.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Recruitment. 3.510 Section 3.510... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be presently...

  17. 10 CFR 5.510 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Recruitment. 5.510 Section 5.510 Energy NUCLEAR REGULATORY... Prohibited § 5.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found...

  18. 29 CFR 36.310 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Recruitment. 36.310 Section 36.310 Labor Office of the... FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 36.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 36.300 through 36.310...

  19. 10 CFR 1042.510 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Recruitment. 1042.510 Section 1042.510 Energy DEPARTMENT... Education Programs or Activities Prohibited § 1042.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees...

  20. TIE2-expressing macrophages limit the therapeutic efficacy of the vascular disrupting agent, combretastatin A4 phosphate in mice.

    OpenAIRE

    Welford, Abigail F.; Biziato, Daniela; Coffelt, Seth B.; Nucera, Silvia; Fisher, Matthew; Pucci, Ferdinando; Di Serio, Clelia; Naldini, Luigi; De Palma, Michele; Tozer, Gillian M.; Lewis, Claire E.

    2011-01-01

    Vascular-disrupting agents (VDAs) such as combretastatin A4 phosphate (CA4P) selectively disrupt blood vessels in tumors and induce tumor necrosis. However, tumors rapidly repopulate after treatment with such compounds. Here, we show that CA4P-induced vessel narrowing, hypoxia, and hemorrhagic necrosis in murine mammary tumors were accompanied by elevated tumor levels of the chemokine CXCL12 and infiltration by proangiogenic TIE2-expressing macrophages (TEMs). Inhibiting TEM recruitment to CA...