WorldWideScience

Sample records for macrophage electronic resource

  1. Electronic Resource Management Systems

    Directory of Open Access Journals (Sweden)

    Mark Ellingsen

    2004-10-01

    Full Text Available Computer applications which deal with electronic resource management (ERM are quite a recent development. They have grown out of the need to manage the burgeoning number of electronic resources particularly electronic journals. Typically, in the early years of e-journal acquisition, library staff provided an easy means of accessing these journals by providing an alphabetical list on a web page. Some went as far as categorising the e-journals by subject and then grouping the journals either on a single web page or by using multiple pages. It didn't take long before it was recognised that it would be more efficient to dynamically generate the pages from a database rather than to continually edit the pages manually. Of course, once the descriptive metadata for an electronic journal was held within a database the next logical step was to provide administrative forms whereby that metadata could be manipulated. This in turn led to demands for incorporating more information and more functionality into the developing application.

  2. Electronic Resource Management and Design

    Science.gov (United States)

    Abrams, Kimberly R.

    2015-01-01

    We have now reached a tipping point at which electronic resources comprise more than half of academic library budgets. Because of the increasing work associated with the ever-increasing number of e-resources, there is a trend to distribute work throughout the library even in the presence of an electronic resources department. In 2013, the author…

  3. Macrophages and mast cells in dystrophic masseter muscle: a light and electron microscopic study

    DEFF Research Database (Denmark)

    Kirkeby, S; Mikkelsen, H

    1988-01-01

    Macrophages and mast cells in masseter muscle from normal and dystrophic mice were studied by light and electron microscopy. Acid phosphatase activity and FITC-dextran were used to identify and describe macrophages. Toluidine blue was used as a marker for mast cells. In dystrophic muscle, the num......Macrophages and mast cells in masseter muscle from normal and dystrophic mice were studied by light and electron microscopy. Acid phosphatase activity and FITC-dextran were used to identify and describe macrophages. Toluidine blue was used as a marker for mast cells. In dystrophic muscle...

  4. Managing electronic resources a LITA guide

    CERN Document Server

    Weir, Ryan O

    2012-01-01

    Informative, useful, current, Managing Electronic Resources: A LITA Guide shows how to successfully manage time, resources, and relationships with vendors and staff to ensure personal, professional, and institutional success.

  5. Electronic Resources Management Project Presentation 2012

    KAUST Repository

    Ramli, Rindra M.

    2012-11-05

    This presentation describes the electronic resources management project undertaken by the KAUST library. The objectives of this project is to migrate information from MS Sharepoint to Millennium ERM module. One of the advantages of this migration is to consolidate all electronic resources into a single and centralized location. This would allow for better information sharing among library staff.

  6. Implementing CORAL: An Electronic Resource Management System

    Science.gov (United States)

    Whitfield, Sharon

    2011-01-01

    A 2010 electronic resource management survey conducted by Maria Collins of North Carolina State University and Jill E. Grogg of University of Alabama Libraries found that the top six electronic resources management priorities included workflow management, communications management, license management, statistics management, administrative…

  7. Electronic Resources Management System: Recommendation Report 2017

    KAUST Repository

    Ramli, Rindra M.

    2017-01-01

    This recommendation report provides an overview of the selection process for the new Electronic Resources Management System. The library has decided to move away from Innovative Interfaces Millennium ERM module. The library reviewed 3 system

  8. Electronic Resources Management Project Presentation 2012

    KAUST Repository

    Ramli, Rindra M.

    2012-01-01

    This presentation describes the electronic resources management project undertaken by the KAUST library. The objectives of this project is to migrate information from MS Sharepoint to Millennium ERM module. One of the advantages of this migration

  9. PRINCIPLES OF CONTENT FORMATION EDUCATIONAL ELECTRONIC RESOURCE

    Directory of Open Access Journals (Sweden)

    О Ю Заславская

    2017-12-01

    Full Text Available The article considers modern possibilities of information and communication technologies for the design of electronic educational resources. The conceptual basis of the open educational multimedia system is based on the modular architecture of the electronic educational resource. The content of the electronic training module can be implemented in several versions of the modules: obtaining information, practical exercises, control. The regularities in the teaching process in modern pedagogical theory are considered: general and specific, and the principles for the formation of the content of instruction at different levels are defined, based on the formulated regularities. On the basis of the analysis, the principles of the formation of the electronic educational resource are determined, taking into account the general and didactic patterns of teaching.As principles of the formation of educational material for obtaining information for the electronic educational resource, the article considers: the principle of methodological orientation, the principle of general scientific orientation, the principle of systemic nature, the principle of fundamentalization, the principle of accounting intersubject communications, the principle of minimization. The principles of the formation of the electronic training module of practical studies in the article include: the principle of systematic and dose based consistency, the principle of rational use of study time, the principle of accessibility. The principles of the formation of the module for monitoring the electronic educational resource can be: the principle of the operationalization of goals, the principle of unified identification diagnosis.

  10. Electronic Resources Management System: Recommendation Report 2017

    KAUST Repository

    Ramli, Rindra M.

    2017-05-01

    This recommendation report provides an overview of the selection process for the new Electronic Resources Management System. The library has decided to move away from Innovative Interfaces Millennium ERM module. The library reviewed 3 system as potential replacements namely: Proquest 360 Resource Manager, Ex Libris Alma and Open Source CORAL ERMS. After comparing and trialling the systems, it was decided to go for Proquest 360 Resource Manager.

  11. CHALLENGES OF ELECTRONIC INFORMATION RESOURCES IN ...

    African Journals Online (AJOL)

    This paper discusses the role of policy for proper and efficient library services in the electronic era. It points out some of the possible dangers of embarking in electronic resources without a proper focus at hand. Thus, it calls for today's librarians and policy makers to brainstorm and come up with working policies suitable to ...

  12. Library training to promote electronic resource usage

    DEFF Research Database (Denmark)

    Frandsen, Tove Faber; Tibyampansha, Dativa; Ibrahim, Glory

    2017-01-01

    Purpose: Increasing the usage of electronic resources is an issue of concern for many libraries all over the world. Several studies stress the importance of information literacy and instruction in order to increase the usage. Design/methodology/approach: The present article presents the results...

  13. Electronic resource management systems a workflow approach

    CERN Document Server

    Anderson, Elsa K

    2014-01-01

    To get to the bottom of a successful approach to Electronic Resource Management (ERM), Anderson interviewed staff at 11 institutions about their ERM implementations. Among her conclusions, presented in this issue of Library Technology Reports, is that grasping the intricacies of your workflow-analyzing each step to reveal the gaps and problems-at the beginning is crucial to selecting and implementing an ERM. Whether the system will be used to fill a gap, aggregate critical data, or replace a tedious manual process, the best solution for your library depends on factors such as your current soft

  14. use of electronic resources by graduate students of the department

    African Journals Online (AJOL)

    respondent's access electronic resources from the internet via Cybercafé .There is a high ... KEY WORDS: Use, Electronic Resources, Graduate Students, Cybercafé. INTRODUCTION ... Faculty of Education, University of Uyo, Uyo. Olu Olat ...

  15. Use of Electronic Resources in a Private University in Nigeria ...

    African Journals Online (AJOL)

    The study examined awareness and constraints in the use of electronic resources by lecturers and students of Ajayi Crowther University, Oyo, Nigeria. It aimed at justifying the resources expended in the provision of electronic resources in terms of awareness, patronage and factors that may be affecting awareness and use ...

  16. Gender Analysis Of Electronic Information Resource Use: The Case ...

    African Journals Online (AJOL)

    Based on the findings the study concluded that access and use of electronic information resources creates a “social digital divide” along gender lines. The study ... Finally, the library needs to change its marketing strategies on the availability of electronic information resources to increase awareness of these resources.

  17. Electronic Resource Management System. Vernetzung von Lizenzinformationen

    Directory of Open Access Journals (Sweden)

    Michaela Selbach

    2014-12-01

    Full Text Available In den letzten zehn Jahren spielen elektronische Ressourcen im Bereich der Erwerbung eine zunehmend wichtige Rolle: Eindeutig lässt sich hier ein Wandel in den Bibliotheken (fort vom reinen Printbestand zu immer größeren E-Only-Beständen feststellen. Die stetig wachsende Menge an E-Ressourcen und deren Heterogenität stellt Bibliotheken vor die Herausforderung, die E-Ressourcen effizient zu verwalten. Nicht nur Bibliotheken, sondern auch verhandlungsführende Institutionen von Konsortial- und Allianzlizenzen benötigen ein geeignetes Instrument zur Verwaltung von Lizenzinformationen, welches den komplexen Anforderungen moderner E-Ressourcen gerecht wird. Die Deutsche Forschungsgemeinschaft (DFG unterstützt ein Projekt des Hochschulbibliothekszentrums des Landes Nordrhein-Westfalen (hbz, der Universitätsbibliothek Freiburg, der Verbundzentrale des Gemeinsamen Bibliotheksverbundes (GBV und der Universitätsbibliothek Frankfurt, in dem ein bundesweit verfügbares Electronic Ressource Managementsystem (ERMS aufgebaut werden soll. Ein solches ERMS soll auf Basis einer zentralen Knowledge Base eine einheitliche Nutzung von Daten zur Lizenzverwaltung elektronischer Ressourcen auf lokaler, regionaler und nationaler Ebene ermöglichen. Statistische Auswertungen, Rechteverwaltung für alle angeschlossenen Bibliotheken, kooperative Datenpflege sowie ein über standardisierte Schnittstellen geführter Datenaustausch stehen bei der Erarbeitung der Anforderungen ebenso im Fokus wie die Entwicklung eines Daten- und Funktionsmodells. In the last few years the importance of electronic resources in library acquisitions has increased significantly. There has been a shift from mere print holdings to both e- and print combinations and even e-only subscriptions. This shift poses a double challenge for libraries: On the one hand they have to provide their e-resource collections to library users in an appealing way, on the other hand they have to manage these

  18. Electronic human resource management: Enhancing or entrancing?

    Directory of Open Access Journals (Sweden)

    Paul Poisat

    2017-07-01

    Full Text Available Orientation: This article provides an investigation into the current level of development of the body of knowledge related to electronic human resource management (e-HRM by means of a qualitative content analysis. Several aspects of e-HRM, namely definitions of e-HRM, the theoretical perspectives around e-HRM, the role of e-HRM, the various types of e-HRM and the requirements for successful e-HRM, are examined. Research purpose: The purpose of the article was to determine the status of e-HRM and examine the studies that report on the link between e-HRM and organisational productivity. Motivation for the study: e-HRM has the capacity to improve organisational efficiency and leverage the role of human resources (HR as a strategic business partner. Main findings: The notion that the implementation of e-HRM will lead to improved organisational productivity is commonly assumed; however, empirical evidence in this regard was found to be limited. Practical/managerial implications: From the results of this investigation it is evident that more research is required to gain a greater understanding of the influence of e-HRM on organisational productivity, as well as to develop measures for assessing this influence. Contribution: This article proposes additional areas to research and measure when investigating the effectiveness of e-HRM. It provides a different lens from which to view e-HRM assessment whilst keeping it within recognised HR measurement parameters (the HR value chain. In addition, it not only provides areas for measuring e-HRM’s influence but also provides important clues as to how the measurements may be approached.

  19. Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells.

    Science.gov (United States)

    Granger, D L; Lehninger, A L

    1982-11-01

    Previous work has shown that injury of neoplastic cells by cytotoxic macrophages (CM) in cell culture is accompanied by inhibition of mitochondrial respiration. We have investigated the nature of this inhibition by studying mitochondrial respiration in CM-injured leukemia L1210 cells permeabilized with digitonin. CM-induced injury affects the mitochondrial respiratory chain proper. Complex I (NADH-coenzyme Q reductase) and complex II (succinate-coenzyme Q reductase) are markedly inhibited. In addition a minor inhibition of cytochrome oxidase was found. Electron transport from alpha-glycerophosphate through the respiratory chain to oxygen is unaffected and permeabilized CM-injured L1210 cells oxidizing this substrate exhibit acceptor control. However, glycerophosphate shuttle activity was found not to occur within CM-injured or uninjured L1210 cells in culture hence, alpha-glycerophosphate is apparently unavailable for mitochondrial oxidation in the intact cell. It is concluded that the failure of respiration of intact neoplastic cells injured by CM is caused by the nearly complete inhibition of complexes I and II of the mitochondrial electron transport chain. The time courses of CM-induced electron transport inhibition and arrest of L1210 cell division are examined and the possible relationship between these phenomena is discussed.

  20. Utilization of electronic information resources by academic staff at ...

    African Journals Online (AJOL)

    The study investigated the utilization of Electronic Information resources by the academic staff of Makerere University in Uganda. It examined the academic staff awareness of the resources available, the types of resources provided by the Makerere University Library, the factors affecting resource utilization. The study was ...

  1. Users satisfaction with electronic information resources and services ...

    African Journals Online (AJOL)

    This study investigated users satisfaction on the use of electronic information resources and services in MTN Net libraries in ABU & UNIBEN. Two objectives and one null hypotheses were formulated and tested with respect to the users' satisfaction on electronic information resources and services in MTN Net libraries in ...

  2. The Role of the Acquisitions Librarian in Electronic Resources Management

    Science.gov (United States)

    Pomerantz, Sarah B.

    2010-01-01

    With the ongoing shift to electronic formats for library resources, acquisitions librarians, like the rest of the profession, must adapt to the rapidly changing landscape of electronic resources by keeping up with trends and mastering new skills related to digital publishing, technology, and licensing. The author sought to know what roles…

  3. Selection and Evaluation of Electronic Resources

    Directory of Open Access Journals (Sweden)

    Doğan Atılgan

    2013-11-01

    Full Text Available Publication boom and issues related to controlling and accession of printed sources have created some problems after World War II. Consequently, publishing industry has encountered the problem of finding possible solution for emerged situation. Industry of electronic publishing has started to improve with the rapid increase of the price of printed sources as well as the problem of publication boom. The first effects of electronic publishing were appeared on the academic and scholarly publications then electronic publishing became a crucial part of all types of publications. As a result of these developments, collection developments and service policies of information centers were also significantly changed. In this article, after a general introduction about selection and evaluation processes of electronic publications, the subscribed databases by a state and a privately owned university in Turkey and their usage were examined.

  4. Improving Electronic Resources through Holistic Budgeting

    Science.gov (United States)

    Kusik, James P.; Vargas, Mark A.

    2009-01-01

    To establish a more direct link between its collections and the educational goals of Saint Xavier University, the Byrne Memorial Library has adopted a "holistic" approach to collection development. This article examines how traditional budget practices influenced the library's selection of resources and describes how holistic collection…

  5. Page 170 Use of Electronic Resources by Undergraduates in Two ...

    African Journals Online (AJOL)

    undergraduate students use electronic resources such as NUC virtual library, HINARI, ... web pages articles from magazines, encyclopedias, pamphlets and other .... of Nigerian university libraries have Internet connectivity, some of the system.

  6. Utilisation of Electronic Information Resources By Lecturers in ...

    African Journals Online (AJOL)

    This study assesses the use of information resources, specifically, electronic databases by lecturers/teachers in Universities and Colleges of Education in South Western Nigeria. Information resources are central to teachers' education. It provides lecturers/teachers access to information that enhances research and ...

  7. Preservation and conservation of electronic information resources of ...

    African Journals Online (AJOL)

    The major holdings of the broadcast libraries of the Nigerian Television Authority (NTA) are electronic information resources; therefore, providing safe places for general management of these resources have aroused interest in the industry in Nigeria for sometimes. The need to study the preservation and conservation of ...

  8. Using XML Technologies to Organize Electronic Reference Resources

    OpenAIRE

    Huser, Vojtech; Del Fiol, Guilherme; Rocha, Roberto A.

    2005-01-01

    Provision of access to reference electronic resources to clinicians is becoming increasingly important. We have created a framework for librarians to manage access to these resources at an enterprise level, rather than at the individual hospital libraries. We describe initial project requirements, implementation details, and some preliminary results.

  9. Euler European Libraries and Electronic Resources in Mathematical Sciences

    CERN Document Server

    The Euler Project. Karlsruhe

    The European Libraries and Electronic Resources (EULER) Project in Mathematical Sciences provides the EulerService site for searching out "mathematical resources such as books, pre-prints, web-pages, abstracts, proceedings, serials, technical reports preprints) and NetLab (for Internet resources), this outstanding engine is capable of simple, full, and refined searches. It also offers a browse option, which responds to entries in the author, keyword, and title fields. Further information about the Project is provided at the EULER homepage.

  10. Building an electronic resource collection a practical guide

    CERN Document Server

    Lee, Stuart D

    2004-01-01

    This practical book guides information professionals step-by-step through building and managing an electronic resource collection. It outlines the range of electronic products currently available in abstracting and indexing, bibliographic, and other services and then describes how to effectively select, evaluate and purchase them.

  11. Organizational matters of competition in electronic educational resources

    Directory of Open Access Journals (Sweden)

    Ирина Карловна Войтович

    2015-12-01

    Full Text Available The article examines the experience of the Udmurt State University in conducting competitions of educational publications and electronic resources. The purpose of such competitions is to provide methodological support to educational process. The main focus is on competition of electronic educational resources. The technology of such contests is discussed through detailed analysis of the main stages of the contest. It is noted that the main task of the preparatory stage of the competition is related to the development of regulations on competition and the definition of criteria for selection of the submitted works. The paper also proposes a system of evaluation criteria of electronic educational resources developed by members of the contest organizing committee and jury members. The article emphasizes the importance of not only the preparatory stages of the competition, but also measures for its completion, aimed at training teachers create quality e-learning resources.

  12. Why and How to Measure the Use of Electronic Resources

    Directory of Open Access Journals (Sweden)

    Jean Bernon

    2008-11-01

    Full Text Available A complete overview of library activity implies a complete and reliable measurement of the use of both electronic resources and printed materials. This measurement is based on three sets of definitions: document types, use types and user types. There is a common model of definitions for printed materials, but a lot of questions and technical issues remain for electronic resources. In 2006 a French national working group studied these questions. It relied on the COUNTER standard, but found it insufficient and pointed out the need for local tools such as web markers and deep analysis of proxy logs. Within the French national consortium COUPERIN, a new working group is testing ERMS, SUSHI standards, Shibboleth authentication, along with COUNTER standards, to improve the counting of the electronic resources use. At this stage this counting is insufficient and its improvement will be a European challenge for the future.

  13. Access to electronic resources by visually impaired people

    Directory of Open Access Journals (Sweden)

    Jenny Craven

    2003-01-01

    Full Text Available Research into access to electronic resources by visually impaired people undertaken by the Centre for Research in Library and Information Management has not only explored the accessibility of websites and levels of awareness in providing websites that adhere to design for all principles, but has sought to enhance understanding of information seeking behaviour of blind and visually impaired people when using digital resources.

  14. Practical guide to electronic resources in the humanities

    CERN Document Server

    Dubnjakovic, Ana

    2010-01-01

    From full-text article databases to digitized collections of primary source materials, newly emerging electronic resources have radically impacted how research in the humanities is conducted and discovered. This book, covering high-quality, up-to-date electronic resources for the humanities, is an easy-to-use annotated guide for the librarian, student, and scholar alike. It covers online databases, indexes, archives, and many other critical tools in key humanities disciplines including philosophy, religion, languages and literature, and performing and visual arts. Succinct overviews of key eme

  15. Discipline, availability of electronic resources and the use of Finnish National Electronic Library - FinELib

    Directory of Open Access Journals (Sweden)

    Sanna Torma

    2004-01-01

    Full Text Available This study elaborated relations between digital library use by university faculty, users' discipline and the availability of key resources in the Finnish National Electronic Library (FinELib, Finnish national digital library, by using nationwide representative survey data. The results show that the perceived availability of key electronic resources by researchers in FinELib was a stronger predictor of the frequency and purpose of use of its services than users' discipline. Regardless of discipline a good perceived provision of central resources led to a more frequent use of FinELib. The satisfaction with the services did not vary with the discipline, but with the perceived availability of resources.

  16. Access to electronic information resources by students of federal ...

    African Journals Online (AJOL)

    The paper discusses access to electronic information resources by students of Federal Colleges of Education in Eha-Amufu and Umunze. Descriptive survey design was used to investigate sample of 526 students. Sampling technique used was a Multi sampling technique. Data for the study were generated using ...

  17. Electronic Commerce Resource Centers. An Industry--University Partnership.

    Science.gov (United States)

    Gulledge, Thomas R.; Sommer, Rainer; Tarimcilar, M. Murat

    1999-01-01

    Electronic Commerce Resource Centers focus on transferring emerging technologies to small businesses through university/industry partnerships. Successful implementation hinges on a strategic operating plan, creation of measurable value for customers, investment in customer-targeted training, and measurement of performance outputs. (SK)

  18. ANALYTICAL REVIEW OF ELECTRONIC RESOURCES FOR THE STUDY OF LATIN

    Directory of Open Access Journals (Sweden)

    Olena Yu. Balalaieva

    2014-04-01

    Full Text Available The article investigates the current state of development of e-learning content in the Latin language. It is noted that the introduction of ICT in the educational space has expanded the possibility of studying Latin, opened access to digital libraries resources, made it possible to use scientific and educational potential and teaching Latin best practices of world's leading universities. A review of foreign and Ukrainian information resources and electronic editions for the study of Latin is given. Much attention was paid to the didactic potential of local and online multimedia courses of Latin, electronic textbooks, workbooks of interactive tests and exercises, various dictionaries and software translators, databases and digital libraries. Based on analysis of the world market of educational services and products the main trends in the development of information resources and electronic books are examined. It was found that multimedia courses with interactive exercises or workbooks with interactive tests, online dictionaries and translators are the most widely represented and demanded. The noticeable lagging of Ukrainian education and computer linguistics in quantitative and qualitative measures in this industry is established. The obvious drawback of existing Ukrainian resources and electronic editions for the study of Latin is their noninteractive nature. The prospects of e-learning content in Latin in Ukraine are outlined.

  19. Adoption and use of electronic information resources by medical ...

    African Journals Online (AJOL)

    This study investigated the adoption and use of electronic information resources by medical science students of the University of Benin. The descriptive survey research design was adopted for the study and 390 students provided the data. Data collected were analysed with descriptive Statistics(Simple percentage and ...

  20. Modern ICT Tools: Online Electronic Resources Sharing Using Web ...

    African Journals Online (AJOL)

    Modern ICT Tools: Online Electronic Resources Sharing Using Web 2.0 and Its Implications For Library And Information Practice In Nigeria. ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader). If you would like more ...

  1. Technical Communicator: A New Model for the Electronic Resources Librarian?

    Science.gov (United States)

    Hulseberg, Anna

    2016-01-01

    This article explores whether technical communicator is a useful model for electronic resources (ER) librarians. The fields of ER librarianship and technical communication (TC) originated and continue to develop in relation to evolving technologies. A review of the literature reveals four common themes for ER librarianship and TC. While the…

  2. MODEL OF AN ELECTRONIC EDUCATIONAL RESOURCE OF NEW GENERATION

    Directory of Open Access Journals (Sweden)

    Anatoliy V. Loban

    2016-01-01

    Full Text Available The mathematical structure of the modular architecture of an electronic educational resource (EER of new generation, which allows to decompose the process of studying the subjects of the course at a hierarchically ordered set of data (knowledge and procedures for manipulating them, to determine the roles of participants of process of training of and technology the development and use of EOR in the study procrate.

  3. End-of-life resource recovery from emerging electronic products

    DEFF Research Database (Denmark)

    Parajuly, Keshav; Habib, Komal; Cimpan, Ciprian

    2016-01-01

    Integrating product design with appropriate end-of-life (EoL) processing is widely recognized to have huge potentials in improving resource recovery from electronic products. In this study, we investigate both the product characteristics and EoL processing of robotic vacuum cleaner (RVC), as a case...... of emerging electronic product, in order to understand the recovery fate of different materials and its linkage to product design. Ten different brands of RVC were dismantled and their material composition and design profiles were studied. Another 125 RVCs (349 kg) were used for an experimental trial...... at a conventional ‘shred-and-separate’ type preprocessing plant in Denmark. A detailed material flow analysis was performed throughout the recycling chain. The results show a mismatch between product design and EoL processing, and the lack of practical implementation of ‘Design for EoL’ thinking. In the best...

  4. Analysis of Human Resources Management Strategy in China Electronic Commerce Enterprises

    Science.gov (United States)

    Shao, Fang

    The paper discussed electronic-commerce's influence on enterprise human resources management, proposed and proved the human resources management strategy which electronic commerce enterprise should adopt from recruitment strategy to training strategy, keeping talent strategy and other ways.

  5. 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

  6. Effects of Electronic Information Resources Skills Training for Lecturers on Pedagogical Practices and Research Productivity

    Science.gov (United States)

    Bhukuvhani, Crispen; Chiparausha, Blessing; Zuvalinyenga, Dorcas

    2012-01-01

    Lecturers use various electronic resources at different frequencies. The university library's information literacy skills workshops and seminars are the main sources of knowledge of accessing electronic resources. The use of electronic resources can be said to have positively affected lecturers' pedagogical practices and their work in general. The…

  7. Electronic Resources and Mission Creep: Reorganizing the Library for the Twenty-First Century

    Science.gov (United States)

    Stachokas, George

    2009-01-01

    The position of electronic resources librarian was created to serve as a specialist in the negotiation of license agreements for electronic resources, but mission creep has added more functions to the routine work of electronic resources such as cataloging, gathering information for collection development, and technical support. As electronic…

  8. Electronic Document Management: A Human Resource Management Case Study

    Directory of Open Access Journals (Sweden)

    Thomas Groenewald

    2004-11-01

    Full Text Available This case study serve as exemplar regarding what can go wrong with the implementation of an electronic document management system. Knowledge agility and knowledge as capital, is outlined against the backdrop of the information society and knowledge economy. The importance of electronic document management and control is sketched thereafter. The literature review is concluded with the impact of human resource management on knowledge agility, which includes references to the learning organisation and complexity theory. The intervention methodology, comprising three phases, follows next. The results of the three phases are presented thereafter. Partial success has been achieved with improving the human efficacy of electronic document management, however the client opted to discontinue the system in use. Opsomming Die gevalle studie dien as voorbeeld van wat kan verkeerd loop met die implementering van ’n elektroniese dokumentbestuur sisteem. Teen die agtergrond van die inligtingsgemeenskap en kennishuishouding word kennissoepelheid en kennis as kapitaal bespreek. Die literatuurstudie word afgesluit met die inpak van menslikehulpbronbestuur op kennissoepelheid, wat ook die verwysings na die leerorganisasie en kompleksietydsteorie insluit. Die metodologie van die intervensie, wat uit drie fases bestaan, volg daarna. Die resultate van die drie fases word vervolgens aangebied. Slegs gedeelte welslae is behaal met die verbetering van die menslike doeltreffendheid ten opsigte van elektroniese dokumentbestuur. Die klient besluit egter om nie voort te gaan om die huidige sisteem te gebruik nie.

  9. Electronic Safety Resource Tools -- Supporting Hydrogen and Fuel Cell Commercialization

    Energy Technology Data Exchange (ETDEWEB)

    Barilo, Nick F.

    2014-09-29

    The Pacific Northwest National Laboratory (PNNL) Hydrogen Safety Program conducted a planning session in Los Angeles, CA on April 1, 2014 to consider what electronic safety tools would benefit the next phase of hydrogen and fuel cell commercialization. A diverse, 20-person team led by an experienced facilitator considered the question as it applied to the eight most relevant user groups. The results and subsequent evaluation activities revealed several possible resource tools that could greatly benefit users. The tool identified as having the greatest potential for impact is a hydrogen safety portal, which can be the central location for integrating and disseminating safety information (including most of the tools identified in this report). Such a tool can provide credible and reliable information from a trustworthy source. Other impactful tools identified include a codes and standards wizard to guide users through a series of questions relating to application and specific features of the requirements; a scenario-based virtual reality training for first responders; peer networking tools to bring users from focused groups together to discuss and collaborate on hydrogen safety issues; and a focused tool for training inspectors. Table ES.1 provides results of the planning session, including proposed new tools and changes to existing tools.

  10. Controlling user access to electronic resources without password

    Science.gov (United States)

    Smith, Fred Hewitt

    2015-06-16

    Described herein are devices and techniques for remotely controlling user access to a restricted computer resource. The process includes pre-determining an association of the restricted computer resource and computer-resource-proximal environmental information. Indicia of user-proximal environmental information are received from a user requesting access to the restricted computer resource. Received indicia of user-proximal environmental information are compared to associated computer-resource-proximal environmental information. User access to the restricted computer resource is selectively granted responsive to a favorable comparison in which the user-proximal environmental information is sufficiently similar to the computer-resource proximal environmental information. In at least some embodiments, the process further includes comparing user-supplied biometric measure and comparing it with a predetermined association of at least one biometric measure of an authorized user. Access to the restricted computer resource is granted in response to a favorable comparison.

  11. Macrophages and dendritic cells in the rat meninges and choroid plexus: three-dimensional localisation by environmental scanning electron microscopy and confocal microscopy.

    Science.gov (United States)

    McMenamin, Paul G; Wealthall, Rosamund J; Deverall, Marie; Cooper, Stephanie J; Griffin, Brendan

    2003-09-01

    The present investigation provides novel information on the topographical distribution of macrophages and dendritic cells (DCs) in normal meninges and choroid plexus of the rat central nervous system (CNS). Whole-mounts of meninges and choroid plexus of Lewis rats were incubated with various anti-leucocyte monoclonal antibodies and either visualised with gold-conjugated secondary antibody followed by silver enhancement and subsequent examination by environmental scanning electron microscopy or by the use of fluorochromes and confocal microscopy. Large numbers of MHC class II(+) putative DCs were identified on the internal or subarachnoid aspect of dural whole-mounts, on the surface of the cortex (pia/arachnoid) and on the surface of the choroid plexus. Occupation of these sites would allow DCs access to cerebrospinal fluid (CSF) and therefore allow antigens into the subarachnoid space and ventricles. By contrast, macrophages were less evident at sites exposed to CSF and were more frequently located within the connective tissue of the dura/arachnoid and choroid plexus stroma and also in a sub-pial location. The present data suggest that DC may be strategically located within the CNS to sample CSF-borne antigens. Furthermore, the data suggest that CNS tissue samples collected without careful removal of the meninges may inadvertently be contaminated by DCs and meningeal macrophages.

  12. The Internet School of Medicine: use of electronic resources by medical trainees and the reliability of those resources.

    Science.gov (United States)

    Egle, Jonathan P; Smeenge, David M; Kassem, Kamal M; Mittal, Vijay K

    2015-01-01

    Electronic sources of medical information are plentiful, and numerous studies have demonstrated the use of the Internet by patients and the variable reliability of these sources. Studies have investigated neither the use of web-based resources by residents, nor the reliability of the information available on these websites. A web-based survey was distributed to surgical residents in Michigan and third- and fourth-year medical students at an American allopathic and osteopathic medical school and a Caribbean allopathic school regarding their preferred sources of medical information in various situations. A set of 254 queries simulating those faced by medical trainees on rounds, on a written examination, or during patient care was developed. The top 5 electronic resources cited by the trainees were evaluated for their ability to answer these questions accurately, using standard textbooks as the point of reference. The respondents reported a wide variety of overall preferred resources. Most of the 73 responding medical trainees favored textbooks or board review books for prolonged studying, but electronic resources are frequently used for quick studying, clinical decision-making questions, and medication queries. The most commonly used electronic resources were UpToDate, Google, Medscape, Wikipedia, and Epocrates. UpToDate and Epocrates had the highest percentage of correct answers (47%) and Wikipedia had the lowest (26%). Epocrates also had the highest percentage of wrong answers (30%), whereas Google had the lowest percentage (18%). All resources had a significant number of questions that they were unable to answer. Though hardcopy books have not been completely replaced by electronic resources, more than half of medical students and nearly half of residents prefer web-based sources of information. For quick questions and studying, both groups prefer Internet sources. However, the most commonly used electronic resources fail to answer clinical queries more than half

  13. Developing Humanities Collections in the Digital Age: Exploring Humanities Faculty Engagement with Electronic and Print Resources

    Science.gov (United States)

    Kachaluba, Sarah Buck; Brady, Jessica Evans; Critten, Jessica

    2014-01-01

    This article is based on quantitative and qualitative research examining humanities scholars' understandings of the advantages and disadvantages of print versus electronic information resources. It explores how humanities' faculty members at Florida State University (FSU) use print and electronic resources, as well as how they perceive these…

  14. Electronic resource management practical perspectives in a new technical services model

    CERN Document Server

    Elguindi, Anne

    2012-01-01

    A significant shift is taking place in libraries, with the purchase of e-resources accounting for the bulk of materials spending. Electronic Resource Management makes the case that technical services workflows need to make a corresponding shift toward e-centric models and highlights the increasing variety of e-formats that are forcing new developments in the field.Six chapters cover key topics, including: technical services models, both past and emerging; staffing and workflow in electronic resource management; implementation and transformation of electronic resource management systems; the ro

  15. Electronic resources access and usage among the postgraduates of ...

    African Journals Online (AJOL)

    ... and usage among the postgraduates of a Nigerian University of Technology. ... faced by postgraduates in using e-resources include takes too much time to find, ... Resources, Access, Use, Postgraduat, Students, University, Technology, Nigeria ... By Country · List All Titles · Free To Read Titles This Journal is Open Access.

  16. Strategic Planning for Electronic Resources Management: A Case Study at Gustavus Adolphus College

    Science.gov (United States)

    Hulseberg, Anna; Monson, Sarah

    2009-01-01

    Electronic resources, the tools we use to manage them, and the needs and expectations of our users are constantly evolving; at the same time, the roles, responsibilities, and workflow of the library staff who manage e-resources are also in flux. Recognizing a need to be more intentional and proactive about how we manage e-resources, the…

  17. impact of the use of electronic resources on research output

    African Journals Online (AJOL)

    manda

    ... Julita Nawe. University of Dar Es Salaam Library, P.O. Box 35092, Dar Es Salaam, Tanzania .... significantly, while 28.3% observed that quality of service to the community had improved .... resources and evaluate them is an important area.

  18. Preservation of and Permanent Access to Electronic Information Resources

    National Research Council Canada - National Science Library

    Hodge, Gail

    2004-01-01

    The rapid growth in the creation and dissemination of electronic information has emphasized the digital environment's speed and ease of dissemination with little regard for its long-term preservation and access...

  19. Electronic conferencing for continuing medical education: a resource survey.

    Science.gov (United States)

    Sternberg, R J

    1986-10-01

    The use of electronic technologies to link participants for education conferences is an option for providers of Continuing Medical Education. In order to profile the kinds of electronic networks currently offering audio- or videoteleconferences for physician audiences, a survey was done during late 1985. The information collected included range of services, fees, and geographic areas served. The results show a broad diversity of providers providing both interactive and didactic programming to both physicians and other health care professionals.

  20. Controlling user access to electronic resources without password

    Science.gov (United States)

    Smith, Fred Hewitt

    2017-08-22

    Described herein are devices and techniques for remotely controlling user access to a restricted computer resource. The process includes obtaining an image from a communication device of a user. An individual and a landmark are identified within the image. Determinations are made that the individual is the user and that the landmark is a predetermined landmark. Access to a restricted computing resource is granted based on the determining that the individual is the user and that the landmark is the predetermined landmark. Other embodiments are disclosed.

  1. Electron beam pasteurised oil palm waste: a potential feed resource

    International Nuclear Information System (INIS)

    Mat Rasol Awang; Hassan Hamdani Mutaat; Tamikazu Kume; Tachibana, H.

    2002-01-01

    Pasteurization of oil palm empty fruit bunch (EFB) was performed using electron beam single sided irradiation. The dose profiles of oil palm EFB samples for different thickness in both directions X and Y were established. The results showed the usual characteristics dose uniformity as sample thickness decreased. The mean average absorbed dose on both sides at the surface and bottom of the samples for different thickness samples lead to establishing depth dose curve. Based on depth dose curve and operation conditions of electron beam machine, the process throughput for pasteurized oil palm EFB were estimated. (Author)

  2. Availability of Electronic Resources for Service Provision in ...

    African Journals Online (AJOL)

    The study also revealed that majority of the University libraries have adequate basic infrastructure for effective electronic information services. ... acquired by the library are put into maximal use by the library clientele, thereby ensuring the achievement of the library's objective which is satisfying the users, information needs.

  3. Utilization of bio-resources by low energy electron beam

    International Nuclear Information System (INIS)

    Kume, Tamikazu

    2003-01-01

    Utilization of bio-resources by radiation has been investigated for recycling the natural resources and reducing the environmental pollution. Polysaccharides such as chitosan and sodium alginate were easily degraded by irradiation and induced various kinds of biological activities, i.g. anti-microbial activity, promotion of plant growth, suppression of heavy metal stress, phytoalexins induction. Radiation degraded chitosan was effective to enhance the growth of plants in tissue culture. It was demonstrated that the liquid sample irradiation system using low energy EB was effective for the preparation of degraded polysaccharides. Methylcellulose (MC) can be crosslinked under certain radiation condition as same as carboxymethylcellulose (CMC) and produced the biodegradable hydrogel for medical and agricultural use. Treatment of soybean seeds by low energy EB enhanced the growth and the number of rhizobia on the root. (author)

  4. Analysis of Pedagogic Potential of Electronic Educational Resources with Elements of Autodidactics

    Directory of Open Access Journals (Sweden)

    Igor A.

    2018-03-01

    Full Text Available Introduction: in recent years didactic properties of electronic educational resources undergo considerable changes, nevertheless, the question of studying of such complete phenomenon as “an electronic educational resource with autodidactics elements” remains open, despite sufficient scientific base of researches of the terms making this concept. Article purpose – determination of essence of electronic educational resources with autodidactics elements. Materials and Methods: the main method of research was the theoretical analysis of the pedagogical and psychological literature on the problem under study. We used the theoretical (analysis, synthesis, comparison and generalization methods, the method of interpretation, pedagogical modeling, and empirical methods (observation, testing, conversation, interview, analysis of students’ performance, pedagogical experiment, peer review. Results: we detected the advantages of electronic educational resources in comparison with traditional ones. The concept of autodidactics as applied to the subject of research is considered. Properties of electronic educational resources with a linear and nonlinear principle of construction are studied.The influence of the principle of construction on the development of the learners’ qualities is shown. We formulated an integral definition of electronic educational resources with elements of autodidactics, namely, the variability, adaptivity and cyclicity of training. A model of the teaching-learning process with electronic educational resources is developed. Discussion and Conclusions: further development of a problem will allow to define whether electronic educational resources with autodidactics elements pedagogical potential for realization of educational and self-educational activity of teachers have, to modify technological procedures taking into account age features of students, their specialties and features of the organization of process of training of

  5. A Study on Developing Evaluation Criteria for Electronic Resources in Evaluation Indicators of Libraries

    Science.gov (United States)

    Noh, Younghee

    2010-01-01

    This study aimed to improve the current state of electronic resource evaluation in libraries. While the use of Web DB, e-book, e-journal, and other e-resources such as CD-ROM, DVD, and micro materials is increasing in libraries, their use is not comprehensively factored into the general evaluation of libraries and may diminish the reliability of…

  6. Managing Selection for Electronic Resources: Kent State University Develops a New System to Automate Selection

    Science.gov (United States)

    Downey, Kay

    2012-01-01

    Kent State University has developed a centralized system that manages the communication and work related to the review and selection of commercially available electronic resources. It is an automated system that tracks the review process, provides selectors with price and trial information, and compiles reviewers' feedback about the resource. It…

  7. Where Do Electronic Books Fit in the College Research Arsenal of Resources?

    Science.gov (United States)

    Barbier, Patricia

    2007-01-01

    Student use of electronic books has become an accepted supplement to traditional resources. Student use and satisfaction was monitored through an online course discussion board. Increased use of electronic books indicate this service is an accepted supplement to the print book collection.

  8. The National Site Licensing of Electronic Resources: An Institutional Perspective

    Directory of Open Access Journals (Sweden)

    Xiaohua Zhu

    2011-06-01

    Full Text Available While academic libraries in most countries are struggling to negotiate with publishers and vendors individually or collaboratively via consortia, a few countries have experimented with a different model, national site licensing (NSL. Because NSL often involves government and large-scale collaboration, it has the potential to solve many problems in the complex licensing world. However, not many nations have adopted it. This study uses historical research approach and the comparative case study research method to explore the seemingly low level of adoption. The cases include the Canadian National Site Licensing Project (CNSLP, the United Kingdom’s National Electronic Site Licensing Initiative (NESLI, and the United States, which has not adopted NSL. The theoretical framework guiding the research design and data collection is W. Richard Scott’s institutional theory, which utilizes three supporting pillars—regulative, normative, and cultural-cognitive—to analyze institutional processes. In this study, the regulative pillar and the normative pillar of NSL adoption— an institutional construction and change—are examined. Data were collected from monographs, research articles, government documents, and relevant websites. Based on the analysis of these cases, a preliminary model is proposed for the adoption of NSL. The factors that support a country’s adoption of NSL include the need for new institutions, a centralized educational policy-making system and funding system, supportive political trends, and the tradition of cooperation. The factors that may prevent a country from adopting NSL include decentralized educational policy and funding, diversity and the large number of institutions, the concern for the “Big Deal,” and the concern for monopoly.

  9. A survey of the use of electronic scientific information resources among medical and dental students

    Directory of Open Access Journals (Sweden)

    Aarnio Matti

    2006-05-01

    Full Text Available Abstract Background To evaluate medical and dental students' utilization of electronic information resources. Methods A web survey sent to 837 students (49.9% responded. Results Twenty-four per cent of medical students and ninteen per cent of dental students searched MEDLINE 2+ times/month for study purposes, and thiry-two per cent and twenty-four per cent respectively for research. Full-text articles were used 2+ times/month by thirty-three per cent of medical and ten per cent of dental students. Twelve per cent of respondents never utilized either MEDLINE or full-text articles. In multivariate models, the information-searching skills among students were significantly associated with use of MEDLINE and full-text articles. Conclusion Use of electronic resources differs among students. Forty percent were non-users of full-text articles. Information-searching skills are correlated with the use of electronic resources, but the level of basic PC skills plays not a major role in using these resources. The student data shows that adequate training in information-searching skills will increase the use of electronic information resources.

  10. Analytical Study of Usage of Electronic Information Resources at Pharmacopoeial Libraries in India

    Directory of Open Access Journals (Sweden)

    Sunil Tyagi

    2014-02-01

    Full Text Available The objective of this study is to know the rate and purpose of the use of e-resource by the scientists at pharmacopoeial libraries in India. Among other things, this study examined the preferences of the scientists toward printed books and journals, electronic information resources, and pattern of using e-resources. Non-probability sampling specially accidental and purposive technique was applied in the collection of primary data through administration of user questionnaire. The sample respondents chosen for the study consists of principle scientific officer, senior scientific officer, scientific officer, and scientific assistant of different division of the laboratories, namely, research and development, pharmaceutical chemistry, pharmacovigilance, pharmacology, pharmacogonosy, and microbiology. The findings of the study reveal the personal experiences and perceptions they have had on practice and research activity using e-resource. The major findings indicate that of the total anticipated participants, 78% indicated that they perceived the ability to use computer for electronic information resources. The data analysis shows that all the scientists belonging to the pharmacopoeial libraries used electronic information resources to address issues relating to drug indexes and compendia, monographs, drugs obtained through online databases, e-journals, and the Internet sources—especially polices by regulatory agencies, contacts, drug promotional literature, and standards.

  11. Considering Point-of-Care Electronic Medical Resources in Lieu of Traditional Textbooks for Medical Education.

    Science.gov (United States)

    Hale, LaDonna S; Wallace, Michelle M; Adams, Courtney R; Kaufman, Michelle L; Snyder, Courtney L

    2015-09-01

    Selecting resources to support didactic courses is a critical decision, and the advantages and disadvantages must be carefully considered. During clinical rotations, students not only need to possess strong background knowledge but also are expected to be proficient with the same evidence-based POC resources used by clinicians. Students place high value on “real world” learning and therefore may place more value on POC resources that they know practicing clinicians use as compared with medical textbooks. The condensed nature of PA education requires students to develop background knowledge and information literacy skills over a short period. One way to build that knowledge and those skills simultaneously is to use POC resources in lieu of traditional medical textbooks during didactic training. Electronic POC resources offer several advantages over traditional textbooks and should be considered as viable options in PA education.

  12. Elektronik Bilgi Kaynaklarının Seçimi / Selection of Electronic Information Resources

    Directory of Open Access Journals (Sweden)

    Pınar Al

    2003-04-01

    Full Text Available For many years, library users have used only from the printed media in order to get the information that they have needed. Today with the widespread use of the Web and the addition of electronic information resources to library collections, the use of information in the electronic environment as well as in printed media is started to be used. In time, such types of information resources as, electronic journals, electronic books, electronic encyclopedias, electronic dictionaries and electronic theses have been added to library collections. In this study, selection criteria that can be used for electronic information resources are discussed and suggestions are provided for libraries that try to select electronic information resources for their collections.

  13. Use of electronic sales data to tailor nutrition education resources for an ethnically diverse population.

    Science.gov (United States)

    Eyles, H; Rodgers, A; Ni Mhurchu, C

    2010-02-01

    Nutrition education may be most effective when personally tailored. Individualised electronic supermarket sales data offer opportunities to tailor nutrition education using shopper's usual food purchases. The present study aimed to use individualised electronic supermarket sales data to tailor nutrition resources for an ethnically diverse population in a large supermarket intervention trial in New Zealand. Culturally appropriate nutrition education resources (i.e. messages and shopping lists) were developed with the target population (through two sets of focus groups) and ethnic researchers. A nutrient database of supermarket products was developed using retrospective sales data and linked to participant sales to allow tailoring by usual food purchases. Modified Heart Foundation Tick criteria were used to identify 'healthier' products in the database suitable for promotion in the resources. Rules were developed to create a monthly report listing the tailored and culturally targeted messages to be sent to each participant, and to produce automated, tailored shopping lists. Culturally targeted nutrition messages (n = 864) and shopping lists (n = 3 formats) were developed. The food and nutrient database (n = 3000 top-selling products) was created using 12 months of retrospective sales data, and comprised 60%'healthier' products. Three months of baseline sales data were used to determine usual food purchases. Tailored resources were successfully mailed to 123 Māori, 52 Pacific and 346 non-Māori non-Pacific participants over the 6-month trial intervention period. Electronic supermarket sales data can be used to tailor nutrition education resources for a large number of ethnically diverse supermarket shoppers.

  14. REVIEW OF MOODLE PLUGINS FOR DESIGNING MULTIMEDIA ELECTRONIC EDUCATIONAL RESOURCES FROM LANGUAGE DISCIPLINES

    Directory of Open Access Journals (Sweden)

    Anton M. Avramchuk

    2015-09-01

    Full Text Available Today the problem of designing multimedia electronic educational resources from language disciplines in Moodle is very important. This system has a lot of different, powerful resources, plugins to facilitate the learning of students with language disciplines. This article presents an overview and comparative analysis of the five Moodle plugins for designing multimedia electronic educational resources from language disciplines. There have been considered their key features and functionality in order to choose the best for studying language disciplines in the Moodle. Plugins are compared by a group of experts according to the criteria: efficiency, functionality and easy use. For a comparative analysis of the plugins it is used the analytic hierarchy process.

  15. Effects of the Use of Electronic Human Resource Management (EHRM Within Human Resource Management (HRM Functions at Universities

    Directory of Open Access Journals (Sweden)

    Chux Gervase Iwu

    2016-09-01

    Full Text Available This study set out to examine the effect of e-hrm systems in assisting human resource practitioners to execute their duties and responsibilities. In comparison to developed economies of the world, information technology adoption in sub-Saharan Africa has not been without certain glitches. Some of the factors that are responsible for these include poor need identification, sustainable funding, and insufficient skills. Besides these factors, there is also the issue of change management and users sticking to what they already know. Although, the above factors seem negative, there is strong evidence that information systems such as electronic human resource management present benefits to an organization. To achieve this, a dual research approach was utilized. Literature assisted immensely in both the development of the conceptual framework upon which the study hinged as well as in the development of the questionnaire items. The study also made use of an interview checklist to guide the participants. The findings reveal a mix of responses that indicate that while there are gains in adopting e-hrm systems, it is wiser to consider supporting resources as well as articulate the needs of the university better before any investment is made.

  16. The Electron Microscopy Outreach Program: A Web-based resource for research and education.

    Science.gov (United States)

    Sosinsky, G E; Baker, T S; Hand, G; Ellisman, M H

    1999-01-01

    We have developed a centralized World Wide Web (WWW)-based environment that serves as a resource of software tools and expertise for biological electron microscopy. A major focus is molecular electron microscopy, but the site also includes information and links on structural biology at all levels of resolution. This site serves to help integrate or link structural biology techniques in accordance with user needs. The WWW site, called the Electron Microscopy (EM) Outreach Program (URL: http://emoutreach.sdsc.edu), provides scientists with computational and educational tools for their research and edification. In particular, we have set up a centralized resource containing course notes, references, and links to image analysis and three-dimensional reconstruction software for investigators wanting to learn about EM techniques either within or outside of their fields of expertise. Copyright 1999 Academic Press.

  17. Identifying and evaluating electronic learning resources for use in adult-gerontology nurse practitioner education.

    Science.gov (United States)

    Thompson, Hilaire J; Belza, Basia; Baker, Margaret; Christianson, Phyllis; Doorenbos, Ardith; Nguyen, Huong

    2014-01-01

    Enhancing existing curricula to meet newly published adult-gerontology advanced practice registered nurse (APRN) competencies in an efficient manner presents a challenge to nurse educators. Incorporating shared, published electronic learning resources (ELRs) in existing or new courses may be appropriate in order to assist students in achieving competencies. The purposes of this project were to (a) identify relevant available ELR for use in enhancing geriatric APRN education and (b) to evaluate the educational utility of identified ELRs based on established criteria. A multilevel search strategy was used. Two independent team members reviewed identified ELR against established criteria to ensure utility. Only resources meeting all criteria were retained. Resources were found for each of the competency areas and included formats such as podcasts, Web casts, case studies, and teaching videos. In many cases, resources were identified using supplemental strategies and not through traditional search or search of existing geriatric repositories. Resources identified have been useful to advanced practice educators in improving lecture and seminar content in a particular topic area and providing students and preceptors with additional self-learning resources. Addressing sustainability within geriatric APRN education is critical for sharing of best practices among educators and for sustainability of teaching and related resources. © 2014.

  18. USE OF ELECTRONIC EDUCATIONAL RESOURCES WHEN TRAINING IN WORK WITH SPREADSHEETS

    Directory of Open Access Journals (Sweden)

    Х А Гербеков

    2017-12-01

    Full Text Available Today the tools for maintaining training courses based on opportunities of information and communication technologies are developed. Practically in all directions of preparation and on all subject matters electronic textbook and self-instruction manuals are created. Nevertheless the industry of computer educational and methodical materials actively develops and gets more and more areas of development and introduction. In this regard more and more urgent is a problem of development of the electronic educational resources adequate to modern educational requirements. Creation and the organization of training courses with use of electronic educational resources in particular on the basis of Internet technologies remains a difficult methodical task.In article the questions connected with development of electronic educational resources for use when studying the substantial line “Information technologies” of a school course of informatics in particular for studying of spreadsheets are considered. Also the analysis of maintenance of a school course and the unified state examination from the point of view of representation of task in him corresponding to the substantial line of studying “Information technologies” on mastering technology of information processing in spreadsheets and the methods of visualization given by means of charts and schedules is carried out.

  19. From Millennium ERM to Proquest 360 Resource Manager: Implementing a new Electronic Resources Management System ERMS in an International Graduate Research University in Saudi Arabia

    KAUST Repository

    Ramli, Rindra M.

    2017-01-01

    An overview of the Recommendation Study and the subsequent Implementation of a new Electronic Resources Management system ERMS in an international graduate research university in the Kingdom of Saudi Arabia. It covers the timeline, deliverables

  20. Availability, Level of Use and Constraints to Use of Electronic Resources by Law Lecturers in Public Universities in Nigeria

    Science.gov (United States)

    Amusa, Oyintola Isiaka; Atinmo, Morayo

    2016-01-01

    (Purpose) This study surveyed the level of availability, use and constraints to use of electronic resources among law lecturers in Nigeria. (Methodology) Five hundred and fifty-two law lecturers were surveyed and four hundred and forty-two responded. (Results) Data analysis revealed that the level of availability of electronic resources for the…

  1. Lysis of autologous human macrophages by lymphokine-activated killer cells: interaction of effector cell and target cell conjugates analyzed by scanning electron microscopy.

    Science.gov (United States)

    Streck, R J; Helinski, E H; Ovak, G M; Pauly, J L

    1990-09-01

    Lymphokine (i.e., interleukin 2; IL-2)-activated killer (LAK) cells derived from normal human blood are known to destroy human tumor target cells. Accordingly, immunotherapy modalities using IL-2, either alone or in combination with LAK cells, have been evaluated for eradicating metastatic cancer. In studies conducted to characterize receptors on LAK cell membrane ultrastructures, we observed that LAK cells kill autologous human monocyte-derived macrophages (M phi). In these experiments, peripheral blood mononuclear cells of a healthy adult donor were cultured to generate LAK cells and autologous non-adherent M phi. Thereafter, conjugates were prepared by incubating for 3 h autologous populations of LAK cells and M phi. Examination of the conjugates by scanning electron microscopy (SEM) identified LAK cell-mediated killing of M phi. Moreover, SEM analysis of the LAK cell membrane architecture identified microvilli-like ultrastructures that provided a physical bridge that joined together the LAK cell and M phi. The immunological mechanism(s) underling LAK cell killing of autologous M phi is not known; nevertheless, these conjugates will provide a useful model to study membrane receptors on ultrastructures that mediate the initial stages of cytolysis that include target cell recognition and cell-to-cell adhesion. The results of our observations and the findings of other investigators who have also demonstrated LAK cell killing of autologous normal human leukocytes are discussed in the context of the association of IL-2 and IL-2-activated killer cells with side effects observed in ongoing clinical trials and with autoimmune disorders.

  2. GUIDELINES FOR EVALUATION OF PSYCHOLOGICAL AND PEDAGOGICAL QUALITY CHARACTERISTICS OF ELECTRONIC EDUCATIONAL RESOURCES

    Directory of Open Access Journals (Sweden)

    Galina P. Lavrentieva

    2014-05-01

    Full Text Available The article highlights the causes of insufficient effective use of electronic learning resources and sets out the guidelines on ways to solve the aforementioned problems. The set of didactic, methodical, psychological, pedagogical, design and ergonomic quality requirements is considered for evaluation, selection and application of information and communication technologies in the educational process. The most appropriate mechanisms for the ICT introduction into the learning process are disclosed as it should meet the specific learning needs of the student and the objectives of the educational process. The guidance for psycho-educational assessment of quality of electronic educational resources is provided. It is argued that the effectiveness of the ICT use is to be improved by means of quality evaluation mechanisms involved into the educational process.

  3. Model of e-learning with electronic educational resources of new generation

    OpenAIRE

    A. V. Loban; D. A. Lovtsov

    2017-01-01

    Purpose of the article: improving of scientific and methodical base of the theory of the е-learning of variability. Methods used: conceptual and logical modeling of the е-learning of variability process with electronic educational resource of new generation and system analysis of the interconnection of the studied subject area, methods, didactics approaches and information and communication technologies means. Results: the formalization complex model of the е-learning of variability with elec...

  4. A systematic review of portable electronic technology for health education in resource-limited settings.

    Science.gov (United States)

    McHenry, Megan S; Fischer, Lydia J; Chun, Yeona; Vreeman, Rachel C

    2017-08-01

    The objective of this study is to conduct a systematic review of the literature of how portable electronic technologies with offline functionality are perceived and used to provide health education in resource-limited settings. Three reviewers evaluated articles and performed a bibliography search to identify studies describing health education delivered by portable electronic device with offline functionality in low- or middle-income countries. Data extracted included: study population; study design and type of analysis; type of technology used; method of use; setting of technology use; impact on caregivers, patients, or overall health outcomes; and reported limitations. Searches yielded 5514 unique titles. Out of 75 critically reviewed full-text articles, 10 met inclusion criteria. Study locations included Botswana, Peru, Kenya, Thailand, Nigeria, India, Ghana, and Tanzania. Topics addressed included: development of healthcare worker training modules, clinical decision support tools, patient education tools, perceptions and usability of portable electronic technology, and comparisons of technologies and/or mobile applications. Studies primarily looked at the assessment of developed educational modules on trainee health knowledge, perceptions and usability of technology, and comparisons of technologies. Overall, studies reported positive results for portable electronic device-based health education, frequently reporting increased provider/patient knowledge, improved patient outcomes in both quality of care and management, increased provider comfort level with technology, and an environment characterized by increased levels of technology-based, informal learning situations. Negative assessments included high investment costs, lack of technical support, and fear of device theft. While the research is limited, portable electronic educational resources present promising avenues to increase access to effective health education in resource-limited settings, contingent

  5. Model of e-learning with electronic educational resources of new generation

    Directory of Open Access Journals (Sweden)

    A. V. Loban

    2017-01-01

    Full Text Available Purpose of the article: improving of scientific and methodical base of the theory of the е-learning of variability. Methods used: conceptual and logical modeling of the е-learning of variability process with electronic educational resource of new generation and system analysis of the interconnection of the studied subject area, methods, didactics approaches and information and communication technologies means. Results: the formalization complex model of the е-learning of variability with electronic educational resource of new generation is developed, conditionally decomposed into three basic components: the formalization model of the course in the form of the thesaurusclassifier (“Author of e-resource”, the model of learning as management (“Coordination. Consultation. Control”, the learning model with the thesaurus-classifier (“Student”. Model “Author of e-resource” allows the student to achieve completeness, high degree of didactic elaboration and structuring of the studied material in triples of variants: modules of education information, practical task and control tasks; the result of the student’s (author’s of e-resource activity is the thesaurus-classifier. Model of learning as management is based on the principle of personal orientation of learning in computer environment and determines the logic of interaction between the lecturer and the student when determining the triple of variants individually for each student; organization of a dialogue between the lecturer and the student for consulting purposes; personal control of the student’s success (report generation and iterative search for the concept of the class assignment in the thesaurus-classifier before acquiring the required level of training. Model “Student” makes it possible to concretize the learning tasks in relation to the personality of the student and to the training level achieved; the assumption of the lecturer about the level of training of a

  6. Review of material recovery from used electric and electronic equipment-alternative options for resource conservation.

    Science.gov (United States)

    Friege, Henning

    2012-09-01

    For waste from electric and electronic equipment, the WEEE Directive stipulates the separate collection of electric and electronic waste. As to new electric and electronic devices, the Restriction of Hazardous Substances (RoHS) Directive bans the use of certain chemicals dangerous for man and environment. From the implementation of the WEEE directive, many unsolved problems have been documented: poor collection success, emission of dangerous substances during collection and recycling, irretrievable loss of valuable metals among others. As to RoHS, data from the literature show a satisfying success. The problems identified in the process can be reduced to some basic dilemmas at the borders between waste management, product policy and chemical safety. The objectives of the WEEE Directive and the specific targets for use and recycling of appliances are not consistent. There is no focus on scarce resources. Extended producer responsibility is not sufficient to guarantee sustainable waste management. Waste management reaches its limits due to problems of implementation but also due to physical laws. A holistic approach is necessary looking at all branch points and sinks in the stream of used products and waste from electric and electronic equipment. This may be done with respect to the general rules for sustainable management of material streams covering the three dimensions of sustainable policy. The relationships between the players in the field of electric and electronic devices have to be taken into account. Most of the problems identified in the implementation process will not be solved by the current amendment of the WEEE Directive.

  7. [Use of internet and electronic resources among Spanish intensivist physicians. First national survey].

    Science.gov (United States)

    Gómez-Tello, V; Latour-Pérez, J; Añón Elizalde, J M; Palencia-Herrejón, E; Díaz-Alersi, R; De Lucas-García, N

    2006-01-01

    Estimate knowledge and use habits of different electronic resources in a sample of Spanish intensivists: Internet, E-mail, distribution lists, and use of portable electronic devices. Self-applied questionnaire. A 50-question questionnaire was distributed among Spanish intensivists through the hospital marketing delegates of a pharmaceutical company and of electronic forums. A total of 682 questionnaires were analyzed (participation: 74%). Ninety six percent of those surveyed used Internet individually: 67% admitted training gap. Internet was the second source of clinical consultations most used (61%), slightly behind consultation to colleagues (65%). The pages consulted most were bibliographic databases (65%) and electronic professional journals (63%), with limited use of Evidence Based Medicine pages (19%). Ninety percent of those surveyed used e-mail regularly in the practice of their profession, although 25% admitted that were not aware of its possibilities. The use of E-mail decreased significantly with increase in age. A total of 62% of the intensivists used distribution lists. Of the rest, 42% were not aware of its existence and 32% admitted they had insufficient training to handle them. Twenty percent of those surveyed had portable electronic devices and 64% considered it useful, basically due to its rapid consultation at bedside. Female gender was a negative predictive factor of its use (OR 0.35; 95% CI 0.2-0.63; p=0.0002). A large majority of the Spanish intensivists use Internet and E-mail. E-mail lists and use of portable devices are still underused resources. There are important gaps in training and infrequent use of essential pages. There are specific groups that require directed educational policies.

  8. High-resolution sub-cellular imaging by correlative NanoSIMS and electron microscopy of amiodarone internalisation by lung macrophages as evidence for drug-induced phospholipidosis.

    Science.gov (United States)

    Jiang, Haibo; Passarelli, Melissa K; Munro, Peter M G; Kilburn, Matt R; West, Andrew; Dollery, Colin T; Gilmore, Ian S; Rakowska, Paulina D

    2017-01-26

    Correlative NanoSIMS and EM imaging of amiodarone-treated macrophages shows the internalisation of the drug at a sub-cellular level and reveals its accumulation within the lysosomes, providing direct evidence for amiodarone-induced phospholipidosis. Chemical fixation using tannic acid effectively seals cellular membranes aiding intracellular retention of diffusible drugs.

  9. The Synthesis of the Hierarchical Structure of Information Resources for Management of Electronic Commerce Entities

    Directory of Open Access Journals (Sweden)

    Krutova Anzhelika S.

    2017-06-01

    Full Text Available The aim of the article is to develop the theoretical bases for the classification and coding of economic information and the scientific justification of the content of information resources of an electronic commerce enterprise. The essence of information resources for management of electronic business entities is investigated. It is proved that the organization of accounting in e-commerce systems is advisable to be built on the basis of two circuits: accounting for financial flows and accounting associated with transformation of business factors in products and services as a result of production activities. There presented a sequence of accounting organization that allows to combine the both circuits in a single information system, which provides a possibility for the integrated replenishment and distributed simultaneous use of the e-commerce system by all groups of users. It is proved that the guarantee of efficient activity of the information management system of electronic commerce entities is a proper systematization of the aggregate of information resources on economic facts and operations of an enterprise in accordance with the management tasks by building the hierarchy of accounting nomenclatures. It is suggested to understand nomenclature as an objective, primary information aggregate concerning a certain fact of the economic activity of an enterprise, which is characterized by minimum requisites, is entered into the database of the information system and is to be reflected in the accounting system. It is proposed to build a database of e-commerce systems as a part of directories (constants, personnel, goods / products, suppliers, buyers and the hierarchy of accounting nomenclatures. The package of documents regulating the organization of accounting at an enterprise should include: the provision on the accounting services, the order on the accounting policy, the job descriptions, the schedules of information exchange, the report card and

  10. ELECTRONIC EDUCATIONAL RESOURCES FOR ONLINE SUPPORT OF MODERN CHEMISTRY CLASSES IN SPECIALIZED SCHOOL

    Directory of Open Access Journals (Sweden)

    Maria D. Tukalo

    2013-09-01

    Full Text Available This article contains material of some modern electronic educational resources that can be used via the Internet to support the modern chemistry classes in specialized school. It was drawn attention to the educational chemical experiments as means of knowledge; simulated key motivational characteristics to enhance students interest for learning subjects, their cognitive and practical activity in the formation of self-reliance and self-creative; commented forecasts for creating of conditions to enhance the creative potential of students in a modern learning environment.

  11. THE MODEL OF LINGUISTIC TEACHERS’ COMPETENCY DEVELOPMENT ON DESIGNING MULTIMEDIA ELECTRONIC EDUCATIONAL RESOURCES IN THE MOODLE SYSTEM

    Directory of Open Access Journals (Sweden)

    Anton M. Avramchuk

    2017-10-01

    Full Text Available The article is devoted to the problem of developing the competency of teachers of language disciplines on designing multimedia electronic educational resources in the Moodle system. The concept of "the competence of teachers of language disciplines on designing multimedia electronic educational resources in the Moodle system" is justified and defined. Identified and characterized the components by which the levels of the competency development of teachers of language disciplines on designing multimedia electronic educational resources in the Moodle system should be assessed. Developed a model for the development of the competency of teachers of language disciplines on designing multimedia electronic educational resources in the Moodle system, which is based on the main scientific approaches, used in adult education, and consists of five blocks: target, informative, technological, diagnostic and effective.

  12. A preliminary categorization of end-of-life electrical and electronic equipment as secondary metal resources

    International Nuclear Information System (INIS)

    Oguchi, Masahiro; Murakami, Shinsuke; Sakanakura, Hirofumi; Kida, Akiko; Kameya, Takashi

    2011-01-01

    Highlights: → End-of-life electrical and electronic equipment (EEE) as secondary metal resources. → The content and the total amount of metals in specific equipment are both important. → We categorized 21 EEE types from contents and total amounts of various metals. → Important equipment types as secondary resources were listed for each metal kind. → Collectability and possible collection systems of various EEE types were discussed. - Abstract: End-of-life electrical and electronic equipment (EEE) has recently received attention as a secondary source of metals. This study examined characteristics of end-of-life EEE as secondary metal resources to consider efficient collection and metal recovery systems according to the specific metals and types of EEE. We constructed an analogy between natural resource development and metal recovery from end-of-life EEE and found that metal content and total annual amount of metal contained in each type of end-of-life EEE should be considered in secondary resource development, as well as the collectability of the end-of-life products. We then categorized 21 EEE types into five groups and discussed their potential as secondary metal resources. Refrigerators, washing machines, air conditioners, and CRT TVs were evaluated as the most important sources of common metals, and personal computers, mobile phones, and video games were evaluated as the most important sources of precious metals. Several types of small digital equipment were also identified as important sources of precious metals; however, mid-size information and communication technology (ICT) equipment (e.g., printers and fax machines) and audio/video equipment were shown to be more important as a source of a variety of less common metals. The physical collectability of each type of EEE was roughly characterized by unit size and number of end-of-life products generated annually. Current collection systems in Japan were examined and potentially appropriate collection

  13. Open-Source Electronic Health Record Systems for Low-Resource Settings: Systematic Review.

    Science.gov (United States)

    Syzdykova, Assel; Malta, André; Zolfo, Maria; Diro, Ermias; Oliveira, José Luis

    2017-11-13

    Despite the great impact of information and communication technologies on clinical practice and on the quality of health services, this trend has been almost exclusive to developed countries, whereas countries with poor resources suffer from many economic and social issues that have hindered the real benefits of electronic health (eHealth) tools. As a component of eHealth systems, electronic health records (EHRs) play a fundamental role in patient management and effective medical care services. Thus, the adoption of EHRs in regions with a lack of infrastructure, untrained staff, and ill-equipped health care providers is an important task. However, the main barrier to adopting EHR software in low- and middle-income countries is the cost of its purchase and maintenance, which highlights the open-source approach as a good solution for these underserved areas. The aim of this study was to conduct a systematic review of open-source EHR systems based on the requirements and limitations of low-resource settings. First, we reviewed existing literature on the comparison of available open-source solutions. In close collaboration with the University of Gondar Hospital, Ethiopia, we identified common limitations in poor resource environments and also the main requirements that EHRs should support. Then, we extensively evaluated the current open-source EHR solutions, discussing their strengths and weaknesses, and their appropriateness to fulfill a predefined set of features relevant for low-resource settings. The evaluation methodology allowed assessment of several key aspects of available solutions that are as follows: (1) integrated applications, (2) configurable reports, (3) custom reports, (4) custom forms, (5) interoperability, (6) coding systems, (7) authentication methods, (8) patient portal, (9) access control model, (10) cryptographic features, (11) flexible data model, (12) offline support, (13) native client, (14) Web client,(15) other clients, (16) code

  14. THE MODEL OF LINGUISTIC TEACHERS’ COMPETENCY DEVELOPMENT ON DESIGNING MULTIMEDIA ELECTRONIC EDUCATIONAL RESOURCES IN THE MOODLE SYSTEM

    OpenAIRE

    Anton M. Avramchuk

    2017-01-01

    The article is devoted to the problem of developing the competency of teachers of language disciplines on designing multimedia electronic educational resources in the Moodle system. The concept of "the competence of teachers of language disciplines on designing multimedia electronic educational resources in the Moodle system" is justified and defined. Identified and characterized the components by which the levels of the competency development of teachers of language disciplines on designing ...

  15. Determining the level of awareness of the physicians in using the variety of electronic information resources and the effecting factors.

    Science.gov (United States)

    Papi, Ahmad; Ghazavi, Roghayeh; Moradi, Salimeh

    2015-01-01

    Understanding of the medical society's from the types of information resources for quick and easy access to information is an imperative task in medical researches and management of the treatment. The present study was aimed to determine the level of awareness of the physicians in using various electronic information resources and the factors affecting it. This study was a descriptive survey. The data collection tool was a researcher-made questionnaire. The study population included all the physicians and specialty physicians of the teaching hospitals affiliated to Isfahan University of Medical Sciences and numbered 350. The sample size based on Morgan's formula was set at 180. The content validity of the tool was confirmed by the library and information professionals and the reliability was 95%. Descriptive statistics were used including the SPSS software version 19. On reviewing the need of the physicians to obtain the information on several occasions, the need for information in conducting the researches was reported by the maximum number of physicians (91.9%) and the usage of information resources, especially the electronic resources, formed 65.4% as the highest rate with regard to meeting the information needs of the physicians. Among the electronic information databases, the maximum awareness was related to Medline with 86.5%. Among the various electronic information resources, the highest awareness (43.3%) was related to the E-journals. The highest usage (36%) was also from the same source. The studied physicians considered the most effective deterrent in the use of electronic information resources as being too busy and lack of time. Despite the importance of electronic information resources for the physician's community, there was no comprehensive knowledge of these resources. This can lead to less usage of these resources. Therefore, careful planning is necessary in the hospital libraries in order to introduce the facilities and full capabilities of the

  16. Success criteria for electronic medical record implementations in low-resource settings: a systematic review.

    Science.gov (United States)

    Fritz, Fleur; Tilahun, Binyam; Dugas, Martin

    2015-03-01

    Electronic medical record (EMR) systems have the potential of supporting clinical work by providing the right information at the right time to the right people and thus make efficient use of resources. This is especially important in low-resource settings where reliable data are also needed to support public health and local supporting organizations. In this systematic literature review, our objectives are to identify and collect literature about success criteria of EMR implementations in low-resource settings and to summarize them into recommendations. Our search strategy relied on PubMed queries and manual bibliography reviews. Studies were included if EMR implementations in low-resource settings were described. The extracted success criteria and measurements were summarized into 7 categories: ethical, financial, functionality, organizational, political, technical, and training. We collected 381 success criteria with 229 measurements from 47 articles out of 223 articles. Most papers were evaluations or lessons learned from African countries, published from 1999 to 2013. Almost half of the EMR systems served a specific disease area like human immunodeficiency virus (HIV). The majority of criteria that were reported dealt with the functionality, followed by organizational issues, and technical infrastructures. Sufficient training and skilled personnel were mentioned in roughly 10%. Political, ethical, and financial considerations did not play a predominant role. More evaluations based on reliable frameworks are needed. Highly reliable data handling methods, human resources and effective project management, as well as technical architecture and infrastructure are all key factors for successful EMR implementation. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Impact of Knowledge Resources Linked to an Electronic Health Record on Frequency of Unnecessary Tests and Treatments

    Science.gov (United States)

    Goodman, Kenneth; Grad, Roland; Pluye, Pierre; Nowacki, Amy; Hickner, John

    2012-01-01

    Introduction: Electronic knowledge resources have the potential to rapidly provide answers to clinicians' questions. We sought to determine clinicians' reasons for searching these resources, the rate of finding relevant information, and the perceived clinical impact of the information they retrieved. Methods: We asked general internists, family…

  18. Resource conservation approached with an appropriate collection and upgrade-remanufacturing for used electronic products.

    Science.gov (United States)

    Zlamparet, Gabriel I; Tan, Quanyin; Stevels, A B; Li, Jinhui

    2018-03-01

    This comparative research represents an example for a better conservation of resources by reducing the amount of waste (kg) and providing it more value under the umbrella of remanufacturing. The three discussed cases will expose three issues already addressed separately in the literature. The generation of waste electrical and electronic equipment (WEEE) interacts with the environmental depletion. In this article, we gave the examples of addressed issues under the concept of remanufacturing. Online collection opportunity eliminating classical collection, a business to business (B2B) implementation for remanufactured servers and medical devices. The material reuse (recycling), component sustainability, reuse (part harvesting), product reuse (after repair/remanufacturing) indicates the recovery potential using remanufacturing tool for a better conservation of resources adding more value to the products. Our findings can provide an overview of new system organization for the general collection, market potential and the technological advantages using remanufacturing instead of recycling of WEEE or used electrical and electronic equipment. Copyright © 2017. Published by Elsevier Ltd.

  19. Electronic theses and dissertations: a review of this valuable resource for nurse scholars worldwide.

    Science.gov (United States)

    Goodfellow, L M

    2009-06-01

    A worldwide repository of electronic theses and dissertations (ETDs) could provide worldwide access to the most up-to-date research generated by masters and doctoral students. Until that international repository is established, it is possible to access some of these valuable knowledge resources. ETDs provide a technologically advanced medium with endless multimedia capabilities that far exceed the print and bound copies of theses and dissertations housed traditionally in individual university libraries. CURRENT USE: A growing trend exists for universities worldwide to require graduate students to submit theses or dissertations as electronic documents. However, nurse scholars underutilize ETDs, as evidenced by perusing bibliographic citation lists in many of the research journals. ETDs can be searched for and retrieved through several digital resources such as the Networked Digital Library of Theses and Dissertations (http://www.ndltd.org), ProQuest Dissertations and Theses (http://www.umi.com), the Australasian Digital Theses Program (http://adt.caul.edu.au/) and through individual university web sites and online catalogues. An international repository of ETDs benefits the community of nurse scholars in many ways. The ability to access recent graduate students' research electronically from anywhere in the world is advantageous. For scholars residing in developing countries, access to these ETDs may prove to be even more valuable. In some cases, ETDs are not available for worldwide access and can only be accessed through the university library from which the student graduated. Public access to university library ETD collections is not always permitted. Nurse scholars from both developing and developed countries could benefit from ETDs.

  20. From Millennium ERM to Proquest 360 Resource Manager: Implementing a new Electronic Resources Management System ERMS in an International Graduate Research University in Saudi Arabia

    KAUST Repository

    Ramli, Rindra M.

    2017-05-17

    An overview of the Recommendation Study and the subsequent Implementation of a new Electronic Resources Management system ERMS in an international graduate research university in the Kingdom of Saudi Arabia. It covers the timeline, deliverables and challenges as well as lessons learnt by the Project Team.

  1. Electronic tracking of human resource skills and knowledge, just in time training, manageable due diligence

    Energy Technology Data Exchange (ETDEWEB)

    Kolodziej, M.A. [Quick Test International Inc., (Canada). Canadian Technology Human Resource Board; Baker, O. [KeySpan Energy Canada, Calgary, AB (Canada)

    2001-06-01

    KeySpan Energy Canada is in the process of obtaining recognition of various occupational profiles including pipeline operators, inspectors, and field and plant operators from various certifying organizations. The process of allowing individuals to obtain certification is recognized by Canadian Technology Human Resources Board as a step towards national standards for technologists and technicians. Proven competency is a must for workers in todays oil industry in response to increasingly stringent government safety regulations, environmental concerns and high public scrutiny. Quick Test international Inc. has developed a management tool in collaboration with end users at KeySpan Energy Canada. It is an electronic, Internet based competency tool for tracking personal competencies and maintaining continued competency. Response to the tool has been favourable. 2 refs., 4 figs.

  2. Availability, Use and Constraints to Use of Electronic Information Resources by Postgraduates Students at the University of Ibadan

    Directory of Open Access Journals (Sweden)

    Dare Samuel Adeleke

    2017-12-01

    Full Text Available Availability, awareness and use of electronic resources provide access to authoritative, reliable, accurate and timely access to information. The use of electronic information resources (EIRs can enable innovation in teaching and increase timeliness in research of postgraduate students which will eventual result into encouragement of the expected research-led enquiry in this digital age. The study adopted a descriptive survey design. Samples of 300 of postgraduate students within seven out 13 Faculties were randomly selected. Data were collected using questionnaire designed to elicit response from respondents and data were analyzed using descriptive statistics methods percentages, mean, and standard deviation. Results indicated that internet was ranked most available and used in the university. Low level of usage of electronic resources, in particular, full texts data bases is linked to a number of constraints: Interrupted power supply was ranked highest among other factors as speed and capacity of computers, retrieval of records with high recall and low precision, retrieving records relevant to information need, lack of knowledge of search techniques to retrieve information effectively, non possession of requisite IT skills and problems accessing the internet. The study recommended that usage of electronic resources be made compulsory, intensifying awareness campaigns concerning the availability, training on use of electronic resources and the problem of power outage be addressed.

  3. Using mobile electronic devices to deliver educational resources in developing countries.

    Science.gov (United States)

    Mazal, Jonathan Robert; Ludwig, Rebecca

    2015-01-01

    Developing countries have far fewer trained radiography professionals than developed countries, which exacerbates the limited access to imaging services. The lack of trained radiographers reflects, in part, limited availability of radiographer-specific educational resources. Historically, organizations that provided such resources in the developing world faced challenges related to the limited stock of current materials as well as expenses associated with shipping and delivery. Four mobile electronic devices (MEDs) were loaded with educational content (e-books, PDFs, and digital applications) spanning major radiography topics. The MEDs were distributed to 4 imaging departments in Ghana, India, Nepal, and Nigeria based on evidence of need for radiography-specific resources, as revealed by survey responses. A cost comparison of postal delivery vs digital delivery of educational content was performed. The effectiveness of delivering additional content via Wi-Fi transmission also was evaluated. Feedback was solicited on users' experience with the MEDs as a delivery tool for educational content. An initial average per e-book expense of $30.05, which included the cost of the device, was calculated for the MED delivery method compared with $15.56 for postal delivery of printed materials. The cost of the MED delivery method was reduced to an average of $10.05 for subsequent e-book deliveries. Additional content was successfully delivered via Wi-Fi transmission to all recipients during the 3-month follow-up period. Overall user feedback on the experience was positive, and ideas for enhancing the MED-based method were identified. Using MEDs to deliver radiography-specific educational content appears to be more cost effective than postal delivery of printed materials on a long-term basis. MEDs are more efficient for providing updates to educational materials. Customization of content to department needs, and using projector devices could enhance the usefulness of MEDs for

  4. The electronic encapsulation of knowledge in hydraulics, hydrology and water resources

    Science.gov (United States)

    Abbott, Michael B.

    The rapidly developing practice of encapsulating knowledge in electronic media is shown to lead necessarily to the restructuring of the knowledge itself. The consequences of this for hydraulics, hydrology and more general water-resources management are investigated in particular relation to current process-simulation, real-time control and advice-serving systems. The generic properties of the electronic knowledge encapsulator are described, and attention is drawn to the manner in which knowledge 'goes into hiding' through encapsulation. This property is traced in the simple situations of pure mathesis and in the more complex situations of taxinomia using one example each from hydraulics and hydrology. The consequences for systems architectures are explained, pointing to the need for multi-agent architectures for ecological modelling and for more general hydroinformatics systems also. The relevance of these developments is indicated by reference to ongoing projects in which they are currently being realised. In conclusion, some more general epistemological aspects are considered within the same context. As this contribution is so much concerned with the processes of signification and communication, it has been partly shaped by the theory of semiotics, as popularised by Eco ( A Theory of Semiotics, Indiana University, Bloomington, 1977).

  5. Plastics disassembly versus bulk recycling: engineering design for end-of-life electronics resource recovery.

    Science.gov (United States)

    Rios, Pedro; Stuart, Julie Ann; Grant, Ed

    2003-12-01

    Annual plastic flows through the business and consumer electronics manufacturing supply chain include nearly 3 billion lb of high-value engineering plastics derived from petroleum. The recovery of resource value from this stream presents critical challenges in areas of materials identification and recycling process design that demand new green engineering technologies applied together with life cycle assessment and ecological supply chain analysis to create viable plastics-to-plastics supply cycles. The sustainable recovery of potentially high-value engineering plastics streams requires that recyclers either avoid mixing plastic parts or purify later by separating smaller plastic pieces created in volume reduction (shredding) steps. Identification and separation constitute significant barriers in the plastics-to-plastics recycling value proposition. In the present work, we develop a model that accepts randomly arriving electronic products to study scenarios by which a recycler might identify and separate high-value engineering plastics as well as metals. Using discrete eventsimulation,we compare current mixed plastics recovery with spectrochemical plastic resin identification and subsequent sorting. Our results show that limited disassembly with whole-part identification can produce substantial yields in separated streams of recovered engineering thermoplastics. We find that disassembly with identification does not constitute a bottleneck, but rather, with relatively few workers, can be configured to pull the process and thus decrease maximum staging space requirements.

  6. 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.

  7. SAGES: a suite of freely-available software tools for electronic disease surveillance in resource-limited settings.

    Directory of Open Access Journals (Sweden)

    Sheri L Lewis

    Full Text Available Public health surveillance is undergoing a revolution driven by advances in the field of information technology. Many countries have experienced vast improvements in the collection, ingestion, analysis, visualization, and dissemination of public health data. Resource-limited countries have lagged behind due to challenges in information technology infrastructure, public health resources, and the costs of proprietary software. The Suite for Automated Global Electronic bioSurveillance (SAGES is a collection of modular, flexible, freely-available software tools for electronic disease surveillance in resource-limited settings. One or more SAGES tools may be used in concert with existing surveillance applications or the SAGES tools may be used en masse for an end-to-end biosurveillance capability. This flexibility allows for the development of an inexpensive, customized, and sustainable disease surveillance system. The ability to rapidly assess anomalous disease activity may lead to more efficient use of limited resources and better compliance with World Health Organization International Health Regulations.

  8. [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.

  9. Electronic Human Resources Management (e-HRM Adoption Studies: Past and Future Research

    Directory of Open Access Journals (Sweden)

    Winarto Winarto

    2018-05-01

    Full Text Available Electronic human resource management (e-HRM systems become more widely used by profit and non-profit organization. However, the field currently lacks sound theoretical frameworks that can be useful in addressing a key issue concerning the implementation of e-HRM systems, in particular to obtain a better understanding of the factors influencing the adoption of e-HRM systems. The objective of this paper is to provide a foundation towards the development of a theoretical framework for the implementation of e-HRM systems and develop a conceptual model that would reflect the nature of e-HRM systems’ adoption through systematic literature review. Adopting Crossan and Apaydin’s procedure of systematic review, this paper investigated 21 empirical papers of electronics human resources management, then categorized them into 4 characteristics which influence the adoption; System and technology characteristics; Organizational characteristics; User/individual characteristics, and Environmental and contextual characteristics. Finally, the e-HRM adoption research framework is drawn and based on the framework; avenues for future research are discussed.   Bahasa Indonesia Abstrak: Manajemen sumber daya manusia elektronik (selanjutnya disebut dengan e-HRM semakin banyak digunakan oleh organisasi profit dan nonprofit. Namun, bidang dan topik ini belum memiliki kerangka teori yang mapan, yang dapat digunakan untuk menganalisis isu-isu terkait penerapan e-HRM, terutama mengenai faktor-faktor yang mempengaruhi adopsi sistem e-HRM. Tujuan penelitian ini adalah untuk memberikan landasan bagi pengembangan kerangka teoritis untuk implementasi sistem e-HRM dan mengembangkan model konseptual yang akan menggambarkan adopsi sistem e-HRM melalui tinjauan literatur sistematis. Mengadopsi prosedur dan metode Crossan dan Apaydin untuk melakukan telaah literatur secara sistematis, paper ini menyelidiki 21 publikasi empiris manajemen sumber daya manusia elektronik dari 2

  10. Impact of Electronic Resources and Usage in Academic Libraries in Ghana: Evidence from Koforidua Polytechnic & All Nations University College, Ghana

    Science.gov (United States)

    Akussah, Maxwell; Asante, Edward; Adu-Sarkodee, Rosemary

    2015-01-01

    The study investigates the relationship between impact of electronic resources and its usage in academic libraries in Ghana: evidence from Koforidua Polytechnic & All Nations University College, Ghana. The study was a quantitative approach using questionnaire to gather data and information. A valid response rate of 58.5% was assumed. SPSS…

  11. Utilization of Electronic Information Resources by Undergraduate Students of University of Ibadan: A Case Study of Social Sciences and Education

    Science.gov (United States)

    Owolabi, Sola; Idowu, Oluwafemi A.; Okocha, Foluke; Ogundare, Atinuke Omotayo

    2016-01-01

    The study evaluated utilization of electronic information resources by undergraduates in the Faculties of Education and the Social Sciences in University of Ibadan. The study adopted a descriptive survey design with a study population of 1872 undergraduates in the Faculties of Education and the Social Sciences in University of Ibadan, from which a…

  12. Systematic review of electronic surveillance of infectious diseases with emphasis on antimicrobial resistance surveillance in resource-limited settings.

    Science.gov (United States)

    Rattanaumpawan, Pinyo; Boonyasiri, Adhiratha; Vong, Sirenda; Thamlikitkul, Visanu

    2018-02-01

    Electronic surveillance of infectious diseases involves rapidly collecting, collating, and analyzing vast amounts of data from interrelated multiple databases. Although many developed countries have invested in electronic surveillance for infectious diseases, the system still presents a challenge for resource-limited health care settings. We conducted a systematic review by performing a comprehensive literature search on MEDLINE (January 2000-December 2015) to identify studies relevant to electronic surveillance of infectious diseases. Study characteristics and results were extracted and systematically reviewed by 3 infectious disease physicians. A total of 110 studies were included. Most surveillance systems were developed and implemented in high-income countries; less than one-quarter were conducted in low-or middle-income countries. Information technologies can be used to facilitate the process of obtaining laboratory, clinical, and pharmacologic data for the surveillance of infectious diseases, including antimicrobial resistance (AMR) infections. These novel systems require greater resources; however, we found that using electronic surveillance systems could result in shorter times to detect targeted infectious diseases and improvement of data collection. This study highlights a lack of resources in areas where an effective, rapid surveillance system is most needed. The availability of information technology for the electronic surveillance of infectious diseases, including AMR infections, will facilitate the prevention and containment of such emerging infectious diseases. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  13. The Use of Electronic Resources by Academic Staff at the University of Ilorin, Nigeria

    Science.gov (United States)

    Tella, Adeyinka; Orim, Faith; Ibrahim, Dauda Morenikeji; Memudu, Suleiman Ajala

    2018-01-01

    The use of e-resources is now commonplace among academics in tertiary educational institutions the world over. Many academics including those in the universities are exploring the opportunities of e-resources to facilitate teaching and research. As the use of e-resources is increasing particularly among academics at the University of Ilorin,…

  14. Modeling antecedents of electronic medical record system implementation success in low-resource setting hospitals.

    Science.gov (United States)

    Tilahun, Binyam; Fritz, Fleur

    2015-08-01

    With the increasing implementation of Electronic Medical Record Systems (EMR) in developing countries, there is a growing need to identify antecedents of EMR success to measure and predict the level of adoption before costly implementation. However, less evidence is available about EMR success in the context of low-resource setting implementations. Therefore, this study aims to fill this gap by examining the constructs and relationships of the widely used DeLone and MacLean (D&M) information system success model to determine whether it can be applied to measure EMR success in those settings. A quantitative cross sectional study design using self-administered questionnaires was used to collect data from 384 health professionals working in five governmental hospitals in Ethiopia. The hospitals use a comprehensive EMR system since three years. Descriptive and structural equation modeling methods were applied to describe and validate the extent of relationship of constructs and mediating effects. The findings of the structural equation modeling shows that system quality has significant influence on EMR use (β = 0.32, P quality has significant influence on EMR use (β = 0.44, P service quality has strong significant influence on EMR use (β = 0.36, P effect of EMR use on user satisfaction was not significant. Both EMR use and user satisfaction have significant influence on perceived net-benefit (β = 0.31, P mediating factor in the relationship between service quality and EMR use (P effect on perceived net-benefit of health professionals. EMR implementers and managers in developing countries are in urgent need of implementation models to design proper implementation strategies. In this study, the constructs and relationships depicted in the updated D&M model were found to be applicable to assess the success of EMR in low resource settings. Additionally, computer literacy was found to be a mediating factor in EMR use and user satisfaction of

  15. 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.

  16. Use and Cost of Electronic Resources in Central Library of Ferdowsi University Based on E-metrics

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Davarpanah

    2012-07-01

    Full Text Available The purpose of this study was to investigate the usage of electronic journals in Ferdowsi University, Iran based on e-metrics. The paper also aimed to emphasize the analysis of cost-benefit and the correlation between the journal impact factors and the usage data. In this study experiences of Ferdowsi University library on licensing and usage of electronic resources was evaluated by providing a cost-benefit analysis based on the cost and usage statistics of electronic resources. Vendor-provided data were also compared with local usage data. The usage data were collected by tracking web-based access locally, and by collecting vender-provided usage data. The data sources were one-year of vendor-supplied e-resource usage data such as Ebsco, Elsevier, Proquest, Emerald, Oxford and Springer and local usage data collected from the Ferdowsi university web server. The study found that actual usage values differ for vendor-provided data and local usage data. Elsevier has got the highest usage degree in searches, sessions and downloads. Statistics also showed that a small number of journals satisfy significant amount of use while the majority of journals were used less frequent and some were never used at all. The users preferred the PDF rather than HTML format. The data in subject profile suggested that the provided e-resources were best suited to certain subjects. There was no correlation between IF and electronic journal use. Monitoring the usage of e-resources gained increasing importance for acquisition policy and budget decisions. The article provided information about local metrics for the six surveyed vendors/publishers, e.g. usage trends, requests per package, cost per use as related to the scientific specialty of the university.

  17. Use and User Perception of Electronic Information Resources: A Case Study of Siva Institute of Frontier Technology, India

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    Velmurugan Chandran

    2013-12-01

    Full Text Available The present study aims to explore the use and user perception of electronic resources in Siva Institute of Frontier Technology, India. A total number of 123 users were taken into account for the study through a questionnaire-based survey method. A well-structured questionnaire was designed and distributed to the selected 200 students and staff members. 123 copies of the questionnaires were returned dully filled in and the overall response rate was 61.50 percent. The questionnaire contained both open- and close-ended questions. The collected data were classified, analyzed, and tabulated by using simple statistical methods. This study covers the impact of electronic resources on students and faculty in their academic pursuit.

  18. Challenges in the implementation of an electronic surveillance system in a resource-limited setting: Alerta, in Peru

    Directory of Open Access Journals (Sweden)

    Soto Giselle

    2008-11-01

    Full Text Available Abstract Background Infectious disease surveillance is a primary public health function in resource-limited settings. In 2003, an electronic disease surveillance system (Alerta was established in the Peruvian Navy with support from the U.S. Naval Medical Research Center Detachment (NMRCD. Many challenges arose during the implementation process, and a variety of solutions were applied. The purpose of this paper is to identify and discuss these issues. Methods This is a retrospective description of the Alerta implementation. After a thoughtful evaluation according to the Centers for Disease Control and Prevention (CDC guidelines, the main challenges to implementation were identified and solutions were devised in the context of a resource-limited setting, Peru. Results After four years of operation, we have identified a number of challenges in implementing and operating this electronic disease surveillance system. These can be divided into the following categories: (1 issues with personnel and stakeholders; (2 issues with resources in a developing setting; (3 issues with processes involved in the collection of data and operation of the system; and (4 issues with organization at the central hub. Some of the challenges are unique to resource-limited settings, but many are applicable for any surveillance system. For each of these challenges, we developed feasible solutions that are discussed. Conclusion There are many challenges to overcome when implementing an electronic disease surveillance system, not only related to technology issues. A comprehensive approach is required for success, including: technical support, personnel management, effective training, and cultural sensitivity in order to assure the effective deployment of an electronic disease surveillance system.

  19. RESEARCH OF INFLUENCE OF QUALITY OF ELECTRONIC EDUCATIONAL RESOURCES ON QUALITY OF TRAINING WITH USE OF DISTANCE TECHNOLOGIES

    Directory of Open Access Journals (Sweden)

    H. M. Kravtsov

    2013-03-01

    Full Text Available Communication improving of educational processes requires today new approaches to the management arrangements and forming of educational policy in the field of distance learning, which is based on the use of modern information and communication technologies. An important step in this process is the continuous monitoring of the development and implementation of information technology and, in particular, the distance learning systems in higher educational establishments. The main objective of the monitoring is the impact assessment on the development of distance learning following the state educational standards, curricula, methodical and technical equipment and other factors; factors revelation that influence the implementation and outcomes of distance learning; results comparison of educational institution functioning and distance education systems in order to determine the most efficient ways of its development. The paper presents the analysis results of the dependence of the quality of educational services on the electronic educational resources. Trends in educational services development was studied by comparing the quality influence of electronic educational resources on the quality of educational services of higher pedagogical educational institutions of Ukraine as of 2009-2010 and 2012-2013. Generally, the analysis of the survey results allows evaluating quality of the modern education services as satisfactory and it can be said that almost 70% of the success of their future development depends on the quality of the used electronic educational resources and distance learning systems in particular.

  20. Tracking the Flow of Resources in Electronic Waste - The Case of End-of-Life Computer Hard Disk Drives.

    Science.gov (United States)

    Habib, Komal; Parajuly, Keshav; Wenzel, Henrik

    2015-10-20

    Recovery of resources, in particular, metals, from waste flows is widely seen as a prioritized option to reduce their potential supply constraints in the future. The current waste electrical and electronic equipment (WEEE) treatment system is more focused on bulk metals, where the recycling rate of specialty metals, such as rare earths, is negligible compared to their increasing use in modern products, such as electronics. This study investigates the challenges in recovering these resources in the existing WEEE treatment system. It is illustrated by following the material flows of resources in a conventional WEEE treatment plant in Denmark. Computer hard disk drives (HDDs) containing neodymium-iron-boron (NdFeB) magnets were selected as the case product for this experiment. The resulting output fractions were tracked until their final treatment in order to estimate the recovery potential of rare earth elements (REEs) and other resources contained in HDDs. The results further show that out of the 244 kg of HDDs treated, 212 kg comprising mainly of aluminum and steel can be finally recovered from the metallurgic process. The results further demonstrate the complete loss of REEs in the existing shredding-based WEEE treatment processes. Dismantling and separate processing of NdFeB magnets from their end-use products can be a more preferred option over shredding. However, it remains a technological and logistic challenge for the existing system.

  1. HELP (INFORMATION ELECTRONIC RESOURCE "CHRONICLE OF ONU: DATES, FACTS, EVENTS": HISTORY OF UNIVERSITY IN INFORMATION SPACE

    Directory of Open Access Journals (Sweden)

    А. М. Гавриленко

    2016-03-01

    Object of research is the help information resource "The chronicle of the Odessa national university of I. I. Mechnikov: dates, facts, events". The main objective of our article – to state the main methodological bases of creation of information resource. One of advantages of information resource is possibility of continuous updating and replenishment by new information. Main objective of creation of this information resource is systematization of material on stories of the Odessa national university of I. I. Mechnikov from the date of his basis to the present, ensuring interactive access to information on the main dates, the most significant events in life of university. The base of research are sources on the history of university, chronology of historical development, formation of infrastructure, cadres and scientific researches. In information resource the main stages of development, functioning and transformation of the Odessa University are analyzed, information on its divisions is collected. For creation of this information resource in Scientific library the method of work was developed, the main selection criteria of data are allocated. This information resource have practical value for all who is interested in history of university, historians, scientists-researchers of history of science and the city of Odessa.

  2. Print and Electronic Resources: Usage Statistics at Guru Gobind Singh Indraprastha University Library

    Science.gov (United States)

    Kapoor, Kanta

    2010-01-01

    Purpose: The purpose of this paper is to quantify the use of electronic journals in comparison with the print collections in the Guru Gobind Singh Indraprastha University Library. Design/methodology/approach: A detailed analysis was made of the use of lending services, the Xerox facility and usage of electronic journals such as Science Direct,…

  3. Understanding intention to use electronic information resources: A theoretical extension of the technology acceptance model (TAM).

    Science.gov (United States)

    Tao, Donghua

    2008-11-06

    This study extended the Technology Acceptance Model (TAM) by examining the roles of two aspects of e-resource characteristics, namely, information quality and system quality, in predicting public health students' intention to use e-resources for completing research paper assignments. Both focus groups and a questionnaire were used to collect data. Descriptive analysis, data screening, and Structural Equation Modeling (SEM) techniques were used for data analysis. The study found that perceived usefulness played a major role in determining students' intention to use e-resources. Perceived usefulness and perceived ease of use fully mediated the impact that information quality and system quality had on behavior intention. The research model enriches the existing technology acceptance literature by extending TAM. Representing two aspects of e-resource characteristics provides greater explanatory information for diagnosing problems of system design, development, and implementation.

  4. 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

  5. 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.

  6. 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.

  7. Structures of class A macrophage scavenger receptors. Electron microscopic study of flexible, multidomain, fibrous proteins and determination of the disulfide bond pattern of the scavenger receptor cysteine-rich domain.

    Science.gov (United States)

    Resnick, D; Chatterton, J E; Schwartz, K; Slayter, H; Krieger, M

    1996-10-25

    Structures of secreted forms of the human type I and II class A macrophage scavenger receptors were studied using biochemical and biophysical methods. Proteolytic analysis was used to determine the intramolecular disulfide bonds in the type I-specific scavenger receptor cysteine-rich (SRCR) domain: Cys2-Cys7, Cys3-Cys8, and Cys5-Cys6. This pattern is likely to be shared by the highly homologous domains in the many other members of the SRCR domain superfamily. Electron microscopy using rotary shadowing and negative staining showed that the type I and II receptors are extended molecules whose contour lengths are approximately 440 A. They comprised two adjacent fibrous segments, an alpha-helical coiled-coil ( approximately 230 A, including a contribution from the N-terminal spacer domain) and a collagenous triple helix ( approximately 210 A). The type I molecules also contained a C-terminal globular structure ( approximately 58 x 76 A) composed of three SRCR domains. The fibrous domains were joined by an extremely flexible hinge. The angle between these domains varied from 0 to 180 degrees and depended on the conditions of sample preparation. Unexpectedly, at physiologic pH, the prevalent angle seen using rotary shadowing was 0 degrees , resulting in a structure that is significantly more compact than previously suggested. The apparent juxtaposition of the fibrous domains at neutral pH provides a framework for future structure-function studies of these unusual multiligand receptors.

  8. Building and Managing Electronic Resources in Digital Era in India with Special Reference to IUCAA and NIV, Pune: A Comparative Case Study

    Science.gov (United States)

    Sahu, H. K.; Singh, S. N.

    2015-04-01

    This paper discusses and presents a comparative case study of two libraries in Pune, India, Inter-University Centre for Astronomy and Astrophysics and Information Centre and Library of National Institute of Virology (Indian Council of Medical Research). It compares how both libraries have managed their e-resource collections, including acquisitions, subscriptions, and consortia arrangements, while also developing a collection of their own resources, including pre-prints and publications, video lectures, and other materials in an institutional repository. This study illustrates how difficult it is to manage electronic resources in a developing country like India, even though electronic resources are used more than print resources. Electronic resource management can be daunting, but with a systematic approach, various problems can be solved, and use of the materials will be enhanced.

  9. The level of the usage of the human resource information system and electronic recruitment in Croatian companies

    Directory of Open Access Journals (Sweden)

    Snježana Pivac

    2014-12-01

    Full Text Available Performing business according to contemporary requirements influences companies for continuous usage of modern managerial tools, such as a human resource information system (HRIS and electronic recruitment (ER. Human resources have been recognised as curtail resources and the main source of a competitive advantage in creation of successful business performance. In order to attract and select the top employees, companies use quality information software for attracting internal ones, and electronic recruitment for attracting the best possible external candidates. The main aim of this paper is to research the level of the usage of HRIS and ER within medium-size and large Croatian companies. Moreover, the additional aim of this paper is to evaluate the relationship among the usage of these modern managerial tools and the overall success of human resource management within these companies. For the purpose of this paper, primary and secondary research has been conducted in order to reveal the level of the usage of HRIS and ER as well as the overall success of human resource management in Croatian companies. The companies’ classification (HRIS and ER is done by using the non-hierarchical k-means cluster method as well as the nonparametric Kruskal Wallis test. Further, the companies are ranked by the multicriteria PROMETHEE method. Relevant nonparametric tests are used for testing the overall companies’ HRM. Finally, binary logistic regression is estimated, relating binary variable HRM and HRIS development. After detailed research, it can be concluded that large Croatian companies apply HRIS in majority (with a positive relation to HRM performance, but still require certain degrees of its development.

  10. The role of autophagy in THP-1 macrophages resistance to HIV- vpr-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Hua-ying, E-mail: zhouhuaying_2004@126.com; Zheng, Yu-huang; He, Yan; Chen, Zi; He, Bo

    2017-02-01

    Macrophages are resistant to cell death and are one of HIV reservoirs. HIV viral protein Vpr has the potential to promote infection of and survival of macrophages, which could be a highly significant factor in the development and/or maintenance of macrophage viral reservoirs. However, the impact of vpr on macrophages resistance to apoptosis is yet to be comprehended. Autophagy is a cell survival mechanism under stress state. In this study, we investigated whether autophagy is involved in macrophages resistant to vpr-induced apoptosis. Using the THP1 macrophages, we studied the interconnection between macrophages resistance to apoptosis and autophagy. We found that vpr is able to trigger autophagy in transfected THP-1 macrophages confirmed by electron microscopy (EM) and western blot analysis, and inhibition of autophagy with 3MA increased vpr-induced apoptosis. The results indicate that autophagy may be responsible for maintenance of macrophage HIV reservoirs. - Highlights: • HIV Vpr is able to trigger autophagy in transfected THP-1 macrophages. • Autophagy inhibition increases vpr-transfected THP1-macrophages apoptosis. • Autophagy is involved in THP-1 macrophages resistant to vpr-induced apoptosis.

  11. MendelWeb: An Electronic Science/Math/History Resource for the WWW.

    Science.gov (United States)

    Blumberg, Roger B.

    This paper describes a hypermedia resource, called MendelWeb that integrates elementary biology, discrete mathematics, and the history of science. MendelWeb is constructed from Gregor Menders 1865 paper, "Experiments in Plant Hybridization". An English translation of Mendel's paper, which is considered to mark the birth of classical and…

  12. Helping Patrons Find Locally Held Electronic Resources: An Interlibrary Loan Perspective

    Science.gov (United States)

    Johnston, Pamela

    2016-01-01

    The University of North Texas Libraries provide extensive online access to academic journals through major vendor databases. As illustrated by interlibrary loan borrowing requests for items held in our databases, patrons often have difficulty navigating the available resources. In this study, the Interlibrary Loan staff used data gathered from the…

  13. QR Codes as Finding Aides: Linking Electronic and Print Library Resources

    Science.gov (United States)

    Kane, Danielle; Schneidewind, Jeff

    2011-01-01

    As part of a focused, methodical, and evaluative approach to emerging technologies, QR codes are one of many new technologies being used by the UC Irvine Libraries. QR codes provide simple connections between print and virtual resources. In summer 2010, a small task force began to investigate how QR codes could be used to provide information and…

  14. Eavesdropping on Electronic Guidebooks: Observing Learning Resources in Shared Listening Environments.

    Science.gov (United States)

    Woodruff, Allison; Aoki, Paul M.; Grinter, Rebecca E.; Hurst, Amy; Szymanski, Margaret H.; Thornton, James D.

    This paper describes an electronic guidebook, "Sotto Voce," that enables visitors to share audio information by eavesdropping on each others guidebook activity. The first section discusses the design and implementation of the guidebook device, key aspects of its user interface, the design goals for the audio environment, the eavesdropping…

  15. Development and evolution of The Knowledge Hub for Pathology and related electronic resources.

    Science.gov (United States)

    Hardwick, David F; Sinard, John; Silva, Fred

    2011-06-01

    The Knowledge Hub for Pathology was created to provide authenticated and validated knowledge for United States and Canadian Academy of Pathology members and pathologists worldwide with access to the Web. Using the material presented at the annual meeting of the United States and Canadian Academy of Pathology with existing selection and review procedures ensured that these criteria were met without added costly procedures. Further submissions for courses and research papers are provided in electronic format and funded by universities and hospitals for their creation; thus, the principal costs borne by the United States and Canadian Academy of Pathology are Web site-posting costs. Use has escalated rapidly from 2 million hits in 2002 to 51 million in 2009 with use by 35,000 pathologists from now a total of 180 countries. This true "freemium" model is a successful process as are more traditional continuing professional development course structures such as Anatomic Pathology Electronic Case Series, a "premium" model for learning electronically also sponsored by the United States and Canadian Academy of Pathology. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. An Exploratory study on the use of LibAnswers to Resolve, Track and Monitor Electronic Resources Issues: The KAUST Library experience

    KAUST Repository

    Ramli, Rindra M.

    2017-01-01

    An Exploratory study on KAUST library use of LibAnswers in resolving electronic resources questions received in LibAnswers. It describes the findings of the questions received in LibAnswers. The author made suggestions based on the findings to improve the reference services in responding to e-resources questions.

  17. An Exploratory study on the use of LibAnswers to Resolve, Track and Monitor Electronic Resources Issues: The KAUST Library experience

    KAUST Repository

    Ramli, Rindra M.

    2017-05-03

    An Exploratory study on KAUST library use of LibAnswers in resolving electronic resources questions received in LibAnswers. It describes the findings of the questions received in LibAnswers. The author made suggestions based on the findings to improve the reference services in responding to e-resources questions.

  18. Designing a model of electronic human resource management’s implementation at the Ministry of Communications and Information Technology

    Directory of Open Access Journals (Sweden)

    Mirali Seyednaghavi

    2017-06-01

    Full Text Available : In the first phase of this study a model for electronic human resource management in government agencies based on new public services was explored by using software MAXQDA, then in the second phase, relationship between the elements of the theory were tested using software Smart PLS2. So the aim of this study is to design a model of electronic human resource management’s implementation at the Ministry of Communications and Information Technology. In this regard, according to Strauss and Corbin’s structured plan, five hypotheses were tested. Quantitative data analysis indicates that the pressures of the policies and global perspectives cause to move toward e-HRM. Among the contextual conditions macro structural mechanisms, considerations of actors, governance considerations have a significant impact on the strategy of new public services and therefore lead to the consequences of its implementation in public organizations. The findings suggest that e-HRM does not have a positive and meaningful impact on new public services, and in our country, although the recent political developments have somehow removed the gap between public policy makers, administrators, and the public, but there is still a long way to go.

  19. Preference and Use of Electronic Information and Resources by Blind/Visually Impaired in NCR Libraries in India

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    Shailendra Kumar

    2013-06-01

    Full Text Available This paper aims to determine the preference and use of electronic information and resources by blind/visually impaired users in the leading National Capital Region (NCR libraries of India. Survey methodology has been used as the basic research tool for data collection with the help of questionnaires. The 125 in total users surveyed in all the five libraries were selected randomly on the basis of willingness of the users with experience of working in digital environments to participate in the survey. The survey results were tabulated and analyzed with descriptive statistics methods using Excel software and 'Stata version 11'. The findings reveal that ICT have a positive impact in the lives of people with disabilities as it helps them to work independently and increases the level of confidence among them. The Internet is the most preferred medium of access to information among the majority of blind/visually impaired users. The 'Complexity of content available on the net' is found as the major challenge faced during Internet use by blind users of NCR libraries. 'Audio books on CDs/DVDs and DAISY books' are the most preferred electronic resources among the majority of blind/visually impaired users. This study will help the library professionals and organizations/institutions serving people with disabilities to develop effective library services for blind/visually impaired users in the digital environment on the basis of findings on information usage behavior in the study.

  20. Internet and electronic resources for inflammatory bowel disease: a primer for providers and patients.

    Science.gov (United States)

    Fortinsky, Kyle J; Fournier, Marc R; Benchimol, Eric I

    2012-06-01

    Patients with inflammatory bowel disease (IBD) are increasingly turning to the Internet to research their condition and engage in discourse on their experiences. This has resulted in new dynamics in the relationship between providers and their patients, with misinformation and advertising potentially presenting barriers to the cooperative patient-provider partnership. This article addresses important issues of online IBD-related health information and social media activity, such as quality, reliability, objectivity, and privacy. We reviewed the medical literature on the quality of online information provided to IBD patients, and summarized the most commonly accessed Websites related to IBD. We also assessed the activity on popular social media sites (such as Facebook, Twitter, and YouTube), and evaluated currently available applications for use by IBD patients and providers on mobile phones and tablets. Through our review of the literature and currently available resources, we developed a list of recommended online resources to strengthen patient participation in their care by providing reliable, comprehensive educational material. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

  1. 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.

  2. 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 ...

  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. Electronic medical records in diabetes consultations: participants' gaze as an interactional resource.

    Science.gov (United States)

    Rhodes, Penny; Small, Neil; Rowley, Emma; Langdon, Mark; Ariss, Steven; Wright, John

    2008-09-01

    Two routine consultations in primary care diabetes clinics are compared using extracts from video recordings of interactions between nurses and patients. The consultations were chosen to present different styles of interaction, in which the nurse's gaze was either primarily toward the computer screen or directed more toward the patient. Using conversation analysis, the ways in which nurses shift both gaze and body orientation between the computer screen and patient to influence the style, pace, content, and structure of the consultation were investigated. By examining the effects of different levels of engagement between the electronic medical record and the embodied patient in the consultation room, we argue for the need to consider the contingent nature of the interface of technology and the person in the consultation. Policy initiatives designed to deliver what is considered best-evidenced practice are modified in the micro context of the interactions of the consultation.

  5. Granulometric composition study of mineral resources using opto-electronic devices and Elsieve software system

    Directory of Open Access Journals (Sweden)

    Kaminski Stanislaw

    2016-01-01

    Full Text Available The use of mechanical sieves has a great impact on measurement results because occurrence of anisometric particles causes undercounting the average size. Such errors can be avoided by using opto-electronic measuring devices that enable measurement of particles from 10 μm up to a few dozen millimetres in size. The results of measurement of each particle size fraction are summed up proportionally to its weight with the use of Elsieve software system and for every type of material particle-size distribution can be obtained. The software allows further statistical interpretation of the results. Beam of infrared radiation identifies size of particles and counts them precisely. Every particle is represented by an electronic impulse proportional to its size. Measurement of particles in aqueous suspension that replaces the hydrometer method can be carried out by using the IPS L analyser (range from 0.2 to 600 μm. The IPS UA analyser (range from 0.5 to 2000 μm is designed for measurement in the air. An ultrasonic adapter enables performing measurements of moist and aggregated particles from 0.5 to 1000 μm. The construction and software system allow to determine second dimension of the particle, its shape coefficient and specific surface area. The AWK 3D analyser (range from 0.2 to 31.5 mm is devoted to measurement of various powdery materials with subsequent determination of particle shape. The AWK B analyser (range from 1 to 130 mm measures materials of thick granulation and shape of the grains. The presented method of measurement repeatedly accelerates and facilitates study of granulometric composition.

  6. Gigantocellular macrophagal reaction in epidermoid cancer of the lung in patients exposed to preoperative irradiation

    International Nuclear Information System (INIS)

    Galil-Ogly, G.A.; Kharchenko, V.P.; Poroshin, K.K.; Pereslegin, O.I.; Krylov, L.M.; Ivanov, E.D.

    1980-01-01

    The histologic and electron microscopic study of frequently occurring gigantocellular macrophagal reaction in the stroma of 83 irradiated epidermoid carcinomas of the lung is carried out. It is found that gigantic multinuclear macrophages take part in the resorption of necrotic and corneous masses as well as in the absorption of viable tumour cells. The presence of gigantocellular macrophagal reaction in the stroma of irradiated tumoUr evidences a more favourable prognosis in patients after the combined treatment of epidermoid lung cancer. Gigantocellular macrophagal reaction should be considered as the manifestation of cell antitumour immunity which makes stronger the tumour irradiation damage

  7. 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.

  8. 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.

  9. 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.

  10. Green Supply Chain Collaboration for Fashionable Consumer Electronics Products under Third-Party Power Intervention—A Resource Dependence Perspective

    Directory of Open Access Journals (Sweden)

    Jiuh-Biing Sheu

    2014-05-01

    Full Text Available Under third-party power intervention (TPPI, which increases uncertainty in task environments, complex channel power interplays and restructuring are indispensable among green supply chain members as they move toward sustainable collaborative relationships for increased viability and competitive advantage. From the resource dependence perspective, this work presents a novel conceptual model to investigate the influence of political and social power on channel power restructuring and induced green supply chain collaboration in brander-retailer bidirectional green supply chains of fashionable consumer electronics products (FCEPs. An FCEP refers to the consumer electronics product (e.g., personal computers, mobile phones, computer notebooks, and game consoles with the features of a well-known brand associated, a short product lifecycle, timely and fashionable design fit for market trends, and quick responsiveness to the variations of market demands. The proposed model is tested empirically using questionnaire data obtained from retailers in the FCEP brander-retailer distribution channels. Analytical results reveal that as an extension of political and social power, TPPI positively affects the reciprocal interdependence of dyadic members and reduces power asymmetry, thereby enhancing the collaborative relationship of dyadic members and leading to improved green supply chain performance. Therein, reciprocal interdependence underlying collaborative relationship is the key to reducing the external environmental uncertainties in the TPPI context.

  11. Bacteroides fragilis induce necrosis on mice peritoneal macrophages: In vitro and in vivo assays

    International Nuclear Information System (INIS)

    Vieira, J.M.B.D.; Seabra, S.H.; Vallim, D.C.; Americo, M.A.; Fracallanza, S.E.L.; Vommaro, R.C.; Domingues, R.M.C.P.

    2009-01-01

    Bacteroides fragilis is an anaerobic bacteria component of human intestinal microbiota and agent of infections. In the host B. fragilis interacts with macrophages, which produces toxic radicals like NO. The interaction of activated mice peritoneal macrophages with four strains of B. fragilis was evaluated on this study. Previously was shown that such strains could cause metabolic and morphologic alterations related to macrophage death. In this work propidium iodide staining showed the strains inducing macrophage necrosis in that the labeling was evident. Besides nitroblue tetrazolium test showed that B. fragilis stimulates macrophage to produce oxygen radicals. In vivo assays performed in BalbC mice have results similar to those for in vitro tests as well as scanning electron microscopy, which showed the same surface pore-like structures observed in vitro before. The results revealed that B. fragilis strains studied lead to macrophage death by a process similar to necrosis.

  12. Bacteroides fragilis induce necrosis on mice peritoneal macrophages: In vitro and in vivo assays

    Energy Technology Data Exchange (ETDEWEB)

    Vieira, J.M.B.D., E-mail: jmanya@terra.com.br [Laboratorio de Tecnologia em Cultura de Celulas, UEZO, Rio de Janeiro (Brazil); Laboratorio de Biologia de Anaerobios, IMPPG, UFRJ, Rio de Janeiro (Brazil); Seabra, S.H. [Laboratorio de Tecnologia em Cultura de Celulas, UEZO, Rio de Janeiro (Brazil); Vallim, D.C. [Instituto Oswaldo Cruz, Rio de Janeiro (Brazil); Americo, M.A.; Fracallanza, S.E.L. [Laboratorio de Bacteriologia Medica, IMPPG, UFRJ, Rio de Janeiro (Brazil); Vommaro, R.C. [Laboratorio de Ultra-estrutura Celular Hertha Meyer, IBCCF, UFRJ (Brazil); Domingues, R.M.C.P. [Laboratorio de Biologia de Anaerobios, IMPPG, UFRJ, Rio de Janeiro (Brazil)

    2009-10-02

    Bacteroides fragilis is an anaerobic bacteria component of human intestinal microbiota and agent of infections. In the host B. fragilis interacts with macrophages, which produces toxic radicals like NO. The interaction of activated mice peritoneal macrophages with four strains of B. fragilis was evaluated on this study. Previously was shown that such strains could cause metabolic and morphologic alterations related to macrophage death. In this work propidium iodide staining showed the strains inducing macrophage necrosis in that the labeling was evident. Besides nitroblue tetrazolium test showed that B. fragilis stimulates macrophage to produce oxygen radicals. In vivo assays performed in BalbC mice have results similar to those for in vitro tests as well as scanning electron microscopy, which showed the same surface pore-like structures observed in vitro before. The results revealed that B. fragilis strains studied lead to macrophage death by a process similar to necrosis.

  13. The management of online resources and long-term saving of electronic documents by transfer into the digital space

    Directory of Open Access Journals (Sweden)

    Marius Daniel MAREŞ

    2011-12-01

    The electronic archive refers to the electronic storage system, along with the totality of electronic-type stored documents, while using as storage support any environment that can support storing and from which an electronic document can be presented.

  14. 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.

  15. 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

  16. Development of an Electronic Medical Record Based Alert for Risk of HIV Treatment Failure in a Low-Resource Setting

    Science.gov (United States)

    Puttkammer, Nancy; Zeliadt, Steven; Balan, Jean Gabriel; Baseman, Janet; Destiné, Rodney; Domerçant, Jean Wysler; France, Garilus; Hyppolite, Nathaelf; Pelletier, Valérie; Raphael, Nernst Atwood; Sherr, Kenneth; Yuhas, Krista; Barnhart, Scott

    2014-01-01

    Background The adoption of electronic medical record systems in resource-limited settings can help clinicians monitor patients' adherence to HIV antiretroviral therapy (ART) and identify patients at risk of future ART failure, allowing resources to be targeted to those most at risk. Methods Among adult patients enrolled on ART from 2005–2013 at two large, public-sector hospitals in Haiti, ART failure was assessed after 6–12 months on treatment, based on the World Health Organization's immunologic and clinical criteria. We identified models for predicting ART failure based on ART adherence measures and other patient characteristics. We assessed performance of candidate models using area under the receiver operating curve, and validated results using a randomly-split data sample. The selected prediction model was used to generate a risk score, and its ability to differentiate ART failure risk over a 42-month follow-up period was tested using stratified Kaplan Meier survival curves. Results Among 923 patients with CD4 results available during the period 6–12 months after ART initiation, 196 (21.2%) met ART failure criteria. The pharmacy-based proportion of days covered (PDC) measure performed best among five possible ART adherence measures at predicting ART failure. Average PDC during the first 6 months on ART was 79.0% among cases of ART failure and 88.6% among cases of non-failure (pART initiation were added to PDC, the risk score differentiated between those who did and did not meet failure criteria over 42 months following ART initiation. Conclusions Pharmacy data are most useful for new ART adherence alerts within iSanté. Such alerts offer potential to help clinicians identify patients at high risk of ART failure so that they can be targeted with adherence support interventions, before ART failure occurs. PMID:25390044

  17. Development of an electronic medical record based alert for risk of HIV treatment failure in a low-resource setting.

    Directory of Open Access Journals (Sweden)

    Nancy Puttkammer

    Full Text Available The adoption of electronic medical record systems in resource-limited settings can help clinicians monitor patients' adherence to HIV antiretroviral therapy (ART and identify patients at risk of future ART failure, allowing resources to be targeted to those most at risk.Among adult patients enrolled on ART from 2005-2013 at two large, public-sector hospitals in Haiti, ART failure was assessed after 6-12 months on treatment, based on the World Health Organization's immunologic and clinical criteria. We identified models for predicting ART failure based on ART adherence measures and other patient characteristics. We assessed performance of candidate models using area under the receiver operating curve, and validated results using a randomly-split data sample. The selected prediction model was used to generate a risk score, and its ability to differentiate ART failure risk over a 42-month follow-up period was tested using stratified Kaplan Meier survival curves.Among 923 patients with CD4 results available during the period 6-12 months after ART initiation, 196 (21.2% met ART failure criteria. The pharmacy-based proportion of days covered (PDC measure performed best among five possible ART adherence measures at predicting ART failure. Average PDC during the first 6 months on ART was 79.0% among cases of ART failure and 88.6% among cases of non-failure (p<0.01. When additional information including sex, baseline CD4, and duration of enrollment in HIV care prior to ART initiation were added to PDC, the risk score differentiated between those who did and did not meet failure criteria over 42 months following ART initiation.Pharmacy data are most useful for new ART adherence alerts within iSanté. Such alerts offer potential to help clinicians identify patients at high risk of ART failure so that they can be targeted with adherence support interventions, before ART failure occurs.

  18. Innovative direct energy conversion systems using electronic adiabatic processes of electron fluid in solid conductors: new plants of electrical power and hydrogen gas resources without environmental pollutions

    International Nuclear Information System (INIS)

    Kondoh, Y.; Kondo, M.; Shimoda, K.; Takahashi, T.

    2001-07-01

    It is shown that using a novel recycling process of the environmental thermal energy, innovative permanent auto-working direct energy converter systems (PA-DEC systems) from the environmental thermal to electrical and/or chemical potential (TE/CP) energies, abbreviated as PA-TE/CP-DEC systems, can be used for new auto-working electrical power plants and the plants of the compressible and conveyable hydrogen gas resources at various regions in the whole world, with contributions to the world peace and the economical development in the south part of the world. It is shown that the same physical mechanism by free electrons and electrical potential determined by temperature in conductors, which include semiconductors, leads to the Peltier effect and the Seebeck one. It is experimentally clarified that the long distance separation between two π type elements of the heat absorption (HAS) and the production one (HPS) of the Peltier effect circuit system or between the higher temperature side (HTS) and the lower one (LTS) of the Seebeck effect circuit one does not change in the whole for the both effects. By using present systems, we do not need to use petrified fuels such as coals, oils, and natural gases in order to decrease the greenhouse effect by the CO 2 surrounding the earth. Furthermore, we do not need plats of nuclear fissions that left radiating wastes, i.e., with no environmental pollutions. The PA-TE/CP-DEC systems can be applicable for several km scale systems to the micro ones, such as the plants of the electrical power, the compact transportable hydrogen gas resources, a large heat energy container, which can be settled at far place from thermal energy absorbing area, the refrigerators, the air conditioners, home electrical apparatuses, and further the computer elements. It is shown that the simplest PA-TE/CP-DEC system can be established by using only the Seebeck effect components and the resolving water ones. It is clarified that the externally applied

  19. Consumer reports [electronic resource

    National Research Council Canada - National Science Library

    1942-01-01

    ... only. A limited number of selected reports, advice on product selection and safety alerts are freely available, as are a five year listing of product recalls, a listing of major consumer product...

  20. The electronic Rothamsted Archive (e-RA), an online resource for data from the Rothamsted long-term experiments.

    Science.gov (United States)

    Perryman, Sarah A M; Castells-Brooke, Nathalie I D; Glendining, Margaret J; Goulding, Keith W T; Hawkesford, Malcolm J; Macdonald, Andy J; Ostler, Richard J; Poulton, Paul R; Rawlings, Christopher J; Scott, Tony; Verrier, Paul J

    2018-05-15

    The electronic Rothamsted Archive, e-RA (www.era.rothamsted.ac.uk) provides a permanent managed database to both securely store and disseminate data from Rothamsted Research's long-term field experiments (since 1843) and meteorological stations (since 1853). Both historical and contemporary data are made available via this online database which provides the scientific community with access to a unique continuous record of agricultural experiments and weather measured since the mid-19 th century. Qualitative information, such as treatment and management practices, plans and soil information, accompanies the data and are made available on the e-RA website. e-RA was released externally to the wider scientific community in 2013 and this paper describes its development, content, curation and the access process for data users. Case studies illustrate the diverse applications of the data, including its original intended purposes and recent unforeseen applications. Usage monitoring demonstrates the data are of increasing interest. Future developments, including adopting FAIR data principles, are proposed as the resource is increasingly recognised as a unique archive of data relevant to sustainable agriculture, agroecology and the environment.

  1. 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.

  2. Principles of formation of the content of an educational electronic resource on the basis of general and didactic patterns of learning

    Directory of Open Access Journals (Sweden)

    Ольга Юрьевна Заславская

    2018-12-01

    Full Text Available The article considers the influence of the development of technical means of teaching on the effectiveness of educational and methodical resources. Modern opportunities of information and communication technologies allow creating electronic educational resources that represent educational information that automates the learning process, provide information assistance, if necessary, collect and process statistical information on the degree of development of the content of the school material by schoolchildren, set an individual trajectory of learning, and so on. The main principle of data organization is the division of the training course into separate sections on the thematic elements and components of the learning process. General regularities include laws that encompass the entire didactic system, and in specific (particular cases, those whose actions extend to a separate component (aspect of the system. From the standpoint of the existence of three types of electronic training modules in the aggregate content of the electronic learning resource - information, control and module of practical classes - the principles of the formation of the electronic learning resource, in our opinion, should regulate all these components. Each of the certain principles is considered in the groups: scientific orientation, methodological orientation, systemic nature, accounting of interdisciplinary connections, fundamentalization, systematic and dosage sequence, rational use of study time, accessibility, minimization, operationalization of goals, unified identification diagnosis.

  3. The module of methodical support in system of electronic educational resources as the innovative element of the modern maintenance of formation

    Directory of Open Access Journals (Sweden)

    Ольга Николаевна Крылова

    2009-06-01

    Full Text Available The article introduces some results of research, which were devoted to evaluation of tearches' mobility to introduce innovations in the contents of education. The author considers innovative potential of modules of the methodical support for system of electronic educational resources.

  4. Charting a Course through CORAL: Texas A&M University Libraries' Experience Implementing an Open-Source Electronic Resources Management System

    Science.gov (United States)

    Hartnett, Eric; Beh, Eugenia; Resnick, Taryn; Ugaz, Ana; Tabacaru, Simona

    2013-01-01

    In 2010, after two previous unsuccessful attempts at electronic resources management system (ERMS) implementation, Texas A&M University (TAMU) Libraries set out once again to find an ERMS that would fit its needs. After surveying the field, TAMU Libraries selected the University of Notre Dame Hesburgh Libraries-developed, open-source ERMS,…

  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. Surface plasma functionalization influences macrophage behavior on carbon nanowalls

    Energy Technology Data Exchange (ETDEWEB)

    Ion, Raluca [University of Bucharest, Department of Biochemistry and Molecular Biology, 91-95 Spl. Independentei, 050095 Bucharest (Romania); Vizireanu, Sorin [National Institute for Laser, Plasma and Radiation Physics, 409 Atomistilor, PO Box MG-36, 077125, Magurele, Bucharest (Romania); Stancu, Claudia Elena [National Institute for Laser, Plasma and Radiation Physics, 409 Atomistilor, PO Box MG-36, 077125, Magurele, Bucharest (Romania); Leibniz Institute for Plasma Science and Technology (INP Greifswald), Felix-Hausdorff-Str. 2, 17489 Greifswald (Germany); Luculescu, Catalin [National Institute for Laser, Plasma and Radiation Physics, 409 Atomistilor, PO Box MG-36, 077125, Magurele, Bucharest (Romania); Cimpean, Anisoara, E-mail: anisoara.cimpean@bio.unibuc.ro [University of Bucharest, Department of Biochemistry and Molecular Biology, 91-95 Spl. Independentei, 050095 Bucharest (Romania); Dinescu, Gheorghe [National Institute for Laser, Plasma and Radiation Physics, 409 Atomistilor, PO Box MG-36, 077125, Magurele, Bucharest (Romania)

    2015-03-01

    The surfaces of carbon nanowall samples as scaffolds for tissue engineering applications were treated with oxygen or nitrogen plasma to improve their wettability and to functionalize their surfaces with different functional groups. X-ray photoelectron spectroscopy and water contact angle results illustrated the effective conversion of the carbon nanowall surfaces from hydrophobic to hydrophilic and the incorporation of various amounts of carbon, oxygen and nitrogen functional groups during the treatments. The early inflammatory responses elicited by un-treated and modified carbon nanowall surfaces were investigated by quantifying tumor necrosis factor-alpha and macrophage inflammatory protein-1 alpha released by attached RAW 264.7 macrophage cells. Scanning electron microscopy and fluorescence studies were employed to investigate the changes in macrophage morphology and adhesive properties, while MTT assay was used to quantify cell proliferation. All samples sustained macrophage adhesion and growth. In addition, nitrogen plasma treatment was more beneficial for cell adhesion in comparison with un-modified carbon nanowall surfaces. Instead, oxygen plasma functionalization led to increased macrophage adhesion and spreading suggesting a more activated phenotype, confirmed by elevated cytokine release. Thus, our findings showed that the chemical surface alterations which occur as a result of plasma treatment, independent of surface wettability, affect macrophage response in vitro. - Highlights: • N{sub 2} and O{sub 2} plasma treatments alter the CNW surface chemistry and wettability. • Cells seeded on CNW scaffolds are viable and metabolically active. • Surface functional groups, independent of surface wettability, affect cell response. • O{sub 2} plasma treatment of CNW leads to a more activated macrophage phenotype.

  7. 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.)

  8. Electronics

    Science.gov (United States)

    2001-01-01

    International Acer Incorporated, Hsin Chu, Taiwan Aerospace Industrial Development Corporation, Taichung, Taiwan American Institute of Taiwan, Taipei, Taiwan...Singapore and Malaysia .5 - 4 - The largest market for semiconductor products is the high technology consumer electronics industry that consumes up...Singapore, and Malaysia . A new semiconductor facility costs around $3 billion to build and takes about two years to become operational

  9. Detection of macrophages in rabbit semen and their relationship with semen quality.

    Science.gov (United States)

    Kuželová, Lenka; Vašíček, Jaromír; Rafay, Ján; Chrenek, Peter

    2017-07-15

    We aimed at the evaluating the occurrence of macrophages in rabbit semen and finding possible relationship between macrophage concentration and spermatozoa quality. The concentration of macrophages in semen samples from broiler rabbit males of lines M91 and P91 (n = 30) without overt evidence of genital tract infections was determined using monocyte/macrophage lineage antigen CD14 and flow cytometry. Then the rabbits were assigned into three groups according to the macrophage concentration in semen (MΦ1 group with less than 1 × 10 6 macrophages/mL, MΦ2 group with 1.5-3.5 × 10 6 macrophages/mL and MΦ3 group with more than 8 × 10 6 macrophages/mL). Spermatozoa viability parameters such as occurrence of apoptotic (Yo-Pro-1) and dead/necrotic (propidium iodide) spermatozoa and plasma membrane integrity (PNA-Fluos) were evaluated using flow cytometry. Sperm motility parameters were determined by CASA (Computer Assisted Semen Analysis). Ultrastructural detection of macrophages was performed using transmission electron microscopy. Spermatozoa fertility potential was examined after intravaginal artificial insemination of rabbit doses. Significantly higher proportions of the apoptotic and necrotic spermatozoa and spermatozoa with lower plasma membrane integrity were revealed in the MΦ3 group compared to MΦ1 and MΦ2 groups. The percentage value of total motility and progressive movement was significantly highest in the MΦ1 group, whilst lowest in the MΦ3 group. The conception rate and the kindling rate were significantly decreased in the group with the highest macrophage concentration (MΦ3). Based on our results we can conclude that the abundance of seminal macrophages in the rabbit semen may be closely associated with poor spermatozoa quality. Copyright © 2017. Published by Elsevier Inc.

  10. 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

  11. 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.

  12. Evaluation of three electronic report processing systems for preparing hydrologic reports of the U.S Geological Survey, Water Resources Division

    Science.gov (United States)

    Stiltner, G.J.

    1990-01-01

    In 1987, the Water Resources Division of the U.S. Geological Survey undertook three pilot projects to evaluate electronic report processing systems as a means to improve the quality and timeliness of reports pertaining to water resources investigations. The three projects selected for study included the use of the following configuration of software and hardware: Ventura Publisher software on an IBM model AT personal computer, PageMaker software on a Macintosh computer, and FrameMaker software on a Sun Microsystems workstation. The following assessment criteria were to be addressed in the pilot studies: The combined use of text, tables, and graphics; analysis of time; ease of learning; compatibility with the existing minicomputer system; and technical limitations. It was considered essential that the camera-ready copy produced be in a format suitable for publication. Visual improvement alone was not a consideration. This report consolidates and summarizes the findings of the electronic report processing pilot projects. Text and table files originating on the existing minicomputer system were successfully transformed to the electronic report processing systems in American Standard Code for Information Interchange (ASCII) format. Graphics prepared using a proprietary graphics software package were transferred to all the electronic report processing software through the use of Computer Graphic Metafiles. Graphics from other sources were entered into the systems by scanning paper images. Comparative analysis of time needed to process text and tables by the electronic report processing systems and by conventional methods indicated that, although more time is invested in creating the original page composition for an electronically processed report , substantial time is saved in producing subsequent reports because the format can be stored and re-used by electronic means as a template. Because of the more compact page layouts, costs of printing the reports were 15% to 25

  13. Electronic resources of the rare books and valuable editions department of the Central Scientific Library of the V.N. Karazin Kharkiv National University: open access for research

    Directory of Open Access Journals (Sweden)

    І. К. Журавльова

    2014-12-01

    Full Text Available The article describes tasks that electronic collections of rare books fulfill: broad access for readers to rare and valuable editions providing, preservation of ensuring of the original. On the example of the electronic collection of the Central Scientific Library of the V.N. Karazin Kharkiv National University – «eScriptorium: electronic archive of rare books and manuscripts for research and education» the possibility of the full-text resources of the valuable editions using is shown. The principles of creation, structure, chronological frameworks, directions of adding the documents to the archive are represented. The perspectives of the project development are outlined as well as examples of the digital libraries of the European countries and Ukraine are provided, the actual task of preserving the originals of the rare books of the country is raised, the innovative approaches to serving users with electronic resources are considered. The evidences of cooperation of the Central Scientific Library of the V.N. Karazin Kharkiv National University with the largest world digital libraries: World Digital Library and Europeana are provided.

  14. 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

  15. The use of quality benchmarking in assessing web resources for the dermatology virtual branch library of the National electronic Library for Health (NeLH).

    Science.gov (United States)

    Kamel Boulos, M N; Roudsari, A V; Gordon, C; Muir Gray, J A

    2001-01-01

    In 1998, the U.K. National Health Service Information for Health Strategy proposed the implementation of a National electronic Library for Health to provide clinicians, healthcare managers and planners, patients and the public with easy, round the clock access to high quality, up-to-date electronic information on health and healthcare. The Virtual Branch Libraries are among the most important components of the National electronic Library for Health. They aim at creating online knowledge based communities, each concerned with some specific clinical and other health-related topics. This study is about the envisaged Dermatology Virtual Branch Libraries of the National electronic Library for Health. It aims at selecting suitable dermatology Web resources for inclusion in the forthcoming Virtual Branch Libraries after establishing preliminary quality benchmarking rules for this task. Psoriasis, being a common dermatological condition, has been chosen as a starting point. Because quality is a principal concern of the National electronic Library for Health, the study includes a review of the major quality benchmarking systems available today for assessing health-related Web sites. The methodology of developing a quality benchmarking system has been also reviewed. Aided by metasearch Web tools, candidate resources were hand-selected in light of the reviewed benchmarking systems and specific criteria set by the authors. Over 90 professional and patient-oriented Web resources on psoriasis and dermatology in general are suggested for inclusion in the forthcoming Dermatology Virtual Branch Libraries. The idea of an all-in knowledge-hallmarking instrument for the National electronic Library for Health is also proposed based on the reviewed quality benchmarking systems. Skilled, methodical, organized human reviewing, selection and filtering based on well-defined quality appraisal criteria seems likely to be the key ingredient in the envisaged National electronic Library for

  16. Barriers to electronic access and delivery of educational information in resource constrained public schools: a case of Greater Tubatse Municipality

    CSIR Research Space (South Africa)

    Pholotho, T

    2016-05-01

    Full Text Available Information and Communication Technologies (ICTs) are capable of expanding access to quality education, educational resources and provide teachers with new skills. Nevertheless, a majority of rural public schools have limited ICTs, mainly due...

  17. Electronic Grey Literature in Accelerator Science and Its Allied Subjects : Selected Web Resources for Scientists and Engineers

    CERN Document Server

    Rajendiran, P

    2006-01-01

    Grey literature Web resources in the field of accelerator science and its allied subjects are collected for the scientists and engineers of RRCAT (Raja Ramanna Centre for Advanced Technology). For definition purposes the different types of grey literature are described. The Web resources collected and compiled in this article (with an overview and link for each) specifically focus on technical reports, preprints or e-prints, which meet the main information needs of RRCAT users.

  18. Tick-borne encephalitis virus infection of cultured mouse macrophages

    Czech Academy of Sciences Publication Activity Database

    Ahantarig, A.; Růžek, Daniel; Vancová, Marie; Janowitz, A.; Šťastná, Hana; Tesařová, Martina; Grubhoffer, Libor

    2009-01-01

    Roč. 52, č. 5 (2009), s. 283-290 ISSN 0300-5526 R&D Projects: GA ČR GA524/06/1479; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : tick-borne encephalitis * macrophage s * electron microscopy Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 1.106, year: 2009

  19. [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.

  20. Phagocytosis of Giardia muris by macrophages in Peyer's patch epithelium in mice.

    Science.gov (United States)

    Owen, R L; Allen, C L; Stevens, D P

    1981-08-01

    No mechanism for the initiation of immunological clearance of Giardia from the mammalian intestinal tract has been identified. In normal and nude mice experimentally infected with G. muris, we examined antigen-sampling epithelium over Peyer's patch follicles by electron microscopy for evidence of interaction between G. muris and lymphoid cells. Invading G. muris were found in the epithelium near dying or desquamating columnar cells. Macrophages beneath the basal lamina extended pseudopods into the epithelium, trapping invading G. muris and enclosing them in phagolysosomes. In normal mice, which clear G. muris in 4 to 6 weeks, macrophages containing digested G. muris were surrounded by rosettes of lymphoblasts in the epithelium. In nude mice deficient in lymphocytes, there was apparent hyperplasia of macrophages, which filled the follicle domes, resulting in more frequent entrapment of G. muris but no contact between macrophages and lymphoblasts in the epithelium. In nude mice, which require 6 months to control G. muris infection, lymphoblast contact with macrophages containing distinctive microtubular remnants of G. muris was only identified in the follicle dome. This close physical association of lymphoblasts and macrophages containing G. muris remnants suggests that this macrophage activity represents intraepithelial antigen processing as well as a defense against the effects of the uncontrolled entrance of microorganisms and other antigenic particles into Peyer's patch lymphoid follicles.

  1. Phagocytosis of mast cell granules results in decreased macrophage superoxide production

    Directory of Open Access Journals (Sweden)

    Bobby A. Shah

    1995-01-01

    Full Text Available The mechanism by which phagocytosed mast cell granules (MCGs inhibit macrophage superoxide production has not been defined. In this study, rat peritoneal macrophages were co-incubated with either isolated intact MCGs or MCG-sonicate, and their respiratory burst capacity and morphology were studied. Co-incubation of macrophages with either intact MCGs or MCG-sonicate resulted in a dose-dependent inhibition of superoxide- mediated cytochrome c reduction. This inhibitory effect was evident within 5 min of incubation and with MCG-sonicate was completely reversed when macrophages were washed prior to activation with PMA. In the case of intact MCGs, the inhibitory effect was only partially reversed by washing after a prolonged co-incubation time. Electron microscopic analyses revealed that MCGs were rapidly phagocytosed by macrophages and were subsequently disintegrated within the phagolysosomes. Assay of MCGs for superoxide dismutase (SOD revealed the presence of significant activity of this enzyme. A comparison of normal macrophages and those containing phagocytosed MCGs did not reveal a significant difference in total SOD activity. It is speculated that, although there was no significant increase in total SOD activity in macrophages containing phagocytosed MCGs, the phagocytosed MCGs might cause a transient increase in SOD activity within the phagolysosomes. This transient rise in SOD results in scavenging of the newly generated superoxide. Alternatively, MCG inhibition of NADPH oxidase would explain the reported observations.

  2. Extracellular vesicles from Leishmania-infected macrophages confer an anti-infection cytokine-production profile to naïve macrophages.

    Directory of Open Access Journals (Sweden)

    André Cronemberger-Andrade

    2014-09-01

    Full Text Available Extracellular vesicles (EVs are structures with phospholipid bilayer membranes and 100-1000 nm diameters. These vesicles are released from cells upon activation of surface receptors and/or apoptosis. The production of EVs by dendritic cells, mast cells, macrophages, and B and T lymphocytes has been extensively reported in the literature. EVs may express MHC class II and other membrane surface molecules and carry antigens. The aim of this study was to investigate the role of EVs from Leishmania-infected macrophages as immune modulatory particles.In this work it was shown that BALB/c mouse bone marrow-derived macrophages, either infected in vitro with Leishmania amazonensis or left uninfected, release comparable amounts of 50-300 nm-diameter extracellular vesicles (EVs. The EVs were characterized by flow cytometry and electron microscopy. The incubation of naïve macrophages with these EVs for 48 hours led to a statistically significant increase in the production of the cytokines IL-12, IL-1β, and TNF-α.EVs derived from macrophages infected with L. amazonensis induce other macrophages, which in vivo could be bystander cells, to produce the proinflammatory cytokines IL-12, IL-1β and TNF-α. This could contribute both to modulate the immune system in favor of a Th1 immune response and to the elimination of the Leishmania, leading, therefore, to the control the infection.

  3. Response of macrophages in rat skeletal muscle after eccentric exercise.

    Science.gov (United States)

    Zuo, Qun; Wang, Shu-Chen; Yu, Xin-Kai; Chao, Wei-Wei

    2018-04-01

    Macrophages are known to be important for healing numerous injured tissues depending on their functional phenotypes in response to different stimuli. The objective of this study was to reveal macrophage phenotypic changes involved in exercise-induced skeletal muscle injury and regeneration. Adult male Sprague-Dawley rats experienced one session of downhill running (16° decline, 16 m/min) for 90 min. After exercise the blood and soleus muscles were collected at 0 h, 6 h, 12 h, 1 d, 2 d, 3 d, 1 w and 2 w after exercise, separately. It was showed that CD68 + M1 macrophages mainly infiltrated into muscle necrotic sites at 1-3 d, while CD163 + M2 macrophages were present in muscles from 0 h to 2 weeks after exercise. Using transmission electron microscopy, we observed activated satellite cells 1 d after exercise. Th1-associated transcripts of iNOS and Ccl2 were inhibited post exercise, while COX-2 mRNA was dramatically increased 12 h after running (p < 0.01). M2 phenotype marker Arg-1 increased 12 h and 3 d (p < 0.05, p < 0.01) after exercise, and Clec10a and Mrc2 were up-regulated in muscles 12 h following exercise (p < 0.05, p < 0.05). The data demonstrate the dynamic patterns of macrophage phenotype in skeletal muscle upon eccentric exercise stimuli, and M1 and M2 phenotypes perform different functions during exercise-induced skeletal muscle injury and recovery. Copyright © 2018 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

  4. Clinician‐selected Electronic Information Resources do not Guarantee Accuracy in Answering Primary Care Physicians’ Information Needs. A review of: McKibbon, K. Ann, and Douglas B. Fridsma. “Effectiveness of Clinician‐selected Electronic Information Resources for Answering Primary Care Physicians’ Information Needs.” Journal of the American Medical Informatics Association 13.6 (2006: 653‐9.

    Directory of Open Access Journals (Sweden)

    Martha Ingrid Preddie

    2008-03-01

    Full Text Available Objective – To determine if electronic information resources selected by primary care physicians improve their ability to answer simulated clinical questions.Design – An observational study utilizing hour‐long interviews and think‐aloud protocols.Setting – The offices and clinics of primary care physicians in Canada and the United States.Subjects – Twenty‐five primary care physicians of whom 4 were women, 17 were from Canada, 22 were family physicians,and 24 were board certified.Methods – Participants provided responses to 23 multiple‐choice questions. Each physician then chose two questions and looked for the answers utilizing information resources of their own choice. The search processes, chosen resources and search times were noted. These were analyzed along with data on the accuracy of the answers and certainties related to the answer to each clinical question prior to the search.Main results – Twenty‐three physicians sought answers to 46 simulated clinical questions. Utilizing only electronic information resources, physicians spent a mean of 13.0 (SD 5.5 minutes searching for answers to the questions, an average of 7.3(SD 4.0 minutes for the first question and 5.8 (SD 2.2 minutes to answer the second question. On average, 1.8 resources were utilized per question. Resources that summarized information, such as the Cochrane Database of Systematic Reviews, UpToDate and Clinical Evidence, were favored 39.2% of the time, MEDLINE (Ovid and PubMed 35.7%, and Internet resources including Google 22.6%. Almost 50% of the search and retrieval strategies were keyword‐based, while MeSH, subheadings and limiting were used less frequently. On average, before searching physicians answered 10 of 23 (43.5% questions accurately. For questions that were searched using clinician‐selected electronic resources, 18 (39.1% of the 46 answers were accurate before searching, while 19 (42.1% were accurate after searching. The difference of

  5. Self-Paced Interactive Multimedia Courseware: A Learning Support Resource for Enhancing Electronic Theses and Dissertations Development

    Science.gov (United States)

    Essel, Harry Barton; Osei-Poku, Patrick; Tachie-Menson, Akosua; Opoku-Asare, Nana Afia

    2016-01-01

    Submission of Electronic Theses and Dissertations (ETDs) by postgraduate students has become a common phenomenon in learning environments globally. The purpose of ETDs is to train postgraduate students as knowledge workers in online publishing and also extend their skills beyond word processing. The challenge however, is that many postgraduate…

  6. Web Accessibility Issues for Higher & Further Education. EDNER (Formative Evaluation of the Distributed National Electronic Resource) Project. Issues Paper.

    Science.gov (United States)

    Manchester Metropolitan Univ. (England).

    This issues paper, sixth in a series of eight, is intended to distill formative evaluation questions on topics that are central to the development of the higher and further education information environment in the United Kingdom. In undertaking formative evaluation studies, the Formative Evaluation of the Distributed National Electronic Resource…

  7. Analyzing the Academic Research Trends by Using University Digital Resources: A Bibliometric Study of Electronic Commerce in China

    Science.gov (United States)

    Fatima, Anam; Abbas, Asad; Ming, Wan; Zaheer, Ahmad Nawaz; Akhtar, Masood-ul-Hassan

    2017-01-01

    Technology plays a vital role in every field of life especially in business and education. Electronic commerce (EC) begins in the year of 1991 right after internet was introduced for commercial use. It is known to be the 12th five years' plan (2011 to 2015) of Chinese Ministry of Industry and Information Technology. The main "objective"…

  8. Green Supply Chain Collaboration for Fashionable Consumer Electronics Products under Third-Party Power Intervention—A Resource Dependence Perspective

    OpenAIRE

    Jiuh-Biing Sheu

    2014-01-01

    Under third-party power intervention (TPPI), which increases uncertainty in task environments, complex channel power interplays and restructuring are indispensable among green supply chain members as they move toward sustainable collaborative relationships for increased viability and competitive advantage. From the resource dependence perspective, this work presents a novel conceptual model to investigate the influence of political and social power on channel power restructuring and induced ...

  9. Immunomodulatory role for membrane vesicles released by THP-1 macrophages and respiratory pathogens during macrophage infection.

    Science.gov (United States)

    Volgers, Charlotte; Benedikter, Birke J; Grauls, Gert E; Savelkoul, Paul H M; Stassen, Frank R M

    2017-11-13

    During infection, inflammation is partially driven by the release of mediators which facilitate intercellular communication. Amongst these mediators are small membrane vesicles (MVs) that can be released by both host cells and Gram-negative and -positive bacteria. Bacterial membrane vesicles are known to exert immuno-modulatory and -stimulatory actions. Moreover, it has been proposed that host cell-derived vesicles, released during infection, also have immunostimulatory properties. In this study, we assessed the release and activity of host cell-derived and bacterial MVs during the first hours following infection of THP-1 macrophages with the common respiratory pathogens non-typeable Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa. Using a combination of flow cytometry, tunable resistive pulse sensing (TRPS)-based analysis and electron microscopy, we demonstrated that the release of MVs occurs by both host cells and bacteria during infection. MVs released during infection and bacterial culture were found to induce a strong pro-inflammatory response by naive THP-1 macrophages. Yet, these MVs were also found to induce tolerance of host cells to secondary immunogenic stimuli and to enhance bacterial adherence and the number of intracellular bacteria. Bacterial MVs may play a dual role during infection, as they can both trigger and dampen immune responses thereby contributing to immune defence and bacterial survival.

  10. 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.

  11. 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

  12. 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...

  13. Share and share alike: encouraging the reuse of academic resources through the Scottish electronic Staff Development Library

    Directory of Open Access Journals (Sweden)

    Lorna M. Campbell

    2001-12-01

    Full Text Available The Scottish electronic Staff Development Library (http://www.sesdl.scotcit.acuk is an ongoing collaborative project involving the Universities of Edinburgh, Paisley and Strathclyde which has been funded by SHEFC as part of their current ScotCIT Programme (http:llwww.scotcit.ac.uk. This project is being developed in response to the increasing demand for flexible, high-quality staff development materials.

  14. Reduced number and morphofunctional change of alveolar macrophages in MafB gene-targeted mice.

    Directory of Open Access Journals (Sweden)

    Michiko Sato-Nishiwaki

    Full Text Available Alveolar macrophages (AMs play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD. We previously demonstrated that the transcription factor, MafB, increased in the AMs of mice exposed to cigarette smoke, and in those of human patients with COPD. The aim of this study was to evaluate the role of MafB in AMs using newly established transgenic (TG mice that specifically express dominant negative (DN MafB in macrophages under the control of macrophage scavenger receptor (MSR enhancer-promoter. We performed cell differential analyses in bronchoalveolar lavage cells, morphological analyses with electron microscopy, and flow cytometry-based analyses of surface markers and a phagocytic capacity assay in macrophages. AM number in the TG mice was significantly decreased compared with wild-type (WT mice. Morphologically, the high electron density area in the nucleus increased, the shape of pseudopods on the AMs was altered, and actin filament was less localized in the pseudopods of AMs of TG mice, compared with WT mice. The expression of surface markers, F4/80 and CD11b, on peritoneal macrophages in TG mice was reduced compared with WT mice, while those on AMs remained unchanged. Phagocytic capacity was decreased in AMs from TG mice, compared with WT mice. In conclusion, MafB regulates the phenotype of macrophages with respect to the number of alveolar macrophages, the nuclear compartment, cellular shape, surface marker expression, and phagocytic function. MSR-DN MafB TG mice may present a useful model to clarify the precise role of MafB in macrophages.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. Success factors for implementing and sustaining a mature electronic medical record in a low-resource setting: a case study of iSanté in Haiti.

    Science.gov (United States)

    deRiel, E; Puttkammer, N; Hyppolite, N; Diallo, J; Wagner, S; Honoré, J G; Balan, J G; Celestin, N; Vallès, J S; Duval, N; Thimothé, G; Boncy, J; Coq, N R L; Barnhart, S

    2018-03-01

    Electronic health information systems, including electronic medical records (EMRs), have the potential to improve access to information and quality of care, among other things. Success factors and challenges for novel EMR implementations in low-resource settings have increasingly been studied, although less is known about maturing systems and sustainability. One systematic review identified seven categories of implementation success factors: ethical, financial, functionality, organizational, political, technical and training. This case study applies this framework to iSanté, Haiti's national EMR in use in more than 100 sites and housing records for more than 750 000 patients. The author group, consisting of representatives of different agencies within the Haitian Ministry of Health (MSPP), funding partner the Centers for Disease Control and Prevention (CDC) Haiti, and implementing partner the International Training and Education Center for Health (I-TECH), identify successes and lessons learned according to the seven identified categories, and propose an additional cross-cutting category, sustainability. Factors important for long-term implementation success of complex information systems are balancing investments in hardware and software infrastructure upkeep, user capacity and data quality control; designing and building a system within the context of the greater eHealth ecosystem with a plan for interoperability and data exchange; establishing system governance and strong leadership to support local system ownership and planning for system financing to ensure sustainability. Lessons learned from 10 years of implementation of the iSanté EMR system are relevant to sustainability of a full range of increasingly interrelated information systems (e.g. for laboratory, supply chain, pharmacy and human resources) in the health sector in low-resource settings. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene

  9. 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.

  10. 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.

  11. Fine surface structure of unfixed and hydrated macrophages observed by laser-plasma x-ray contact microscopy

    International Nuclear Information System (INIS)

    Yamamoto, Yoshimasa; Friedman, Herman; Yoshimura, Hideyuki; Kinjo, Yasuhito; Shioda, Seiji; Debari, Kazuhiro; Shinohara, Kunio; Rajyaguru, Jayshree; Richardson, Martin

    2000-01-01

    A compact, high-resolution, laser-plasma, x-ray contact microscope using a table-top Nd:glass laser system has been developed and utilized for the analysis of the surface structure of live macrophages. Fine fluffy surface structures of murine peritoneal macrophages, which were live, hydrolyzed and not sliced and stained, were observed by the x-ray microscope followed by analysis using an atomic force microscopy. In order to compare with other techniques, a scanning electron microscopy (SEM) was utilized to observe the surface structure of the macrophages. The SEM offered a fine whole cell image of the same macrophages, which were fixed and dehydrated, but the surfaces were ruffled and different from that of x-ray images. A standard light microscope was also utilized to observe the shape of live whole macrophages. Light microscopy showed some fluffy surface structures of the macrophages, but the resolution was too low to observe the fine structures. Thus, the findings of fine fluffy surface structures of macrophages by x-ray microscopy provide valuable information for studies of phagocytosis, cell spreading and adherence, which are dependent on the surface structure of macrophages. Furthermore, the present study also demonstrates the usefulness of x-ray microscopy for analysis of structures of living cells

  12. Selection and Evaluation of Electronic Resources Elektronik Kaynakların Seçimi ve Değerlendirilmesi

    Directory of Open Access Journals (Sweden)

    Doğan Atılgan

    2009-12-01

    Full Text Available Publication boom and issues related to controlling and accession of printed sources have created some problems after World War II. Consequently, publishing industry has encountered the problem of finding possible solution for emerged situation. Industry of electronic publishing has started to improve with the rapid increase of the price of printed sources as well as the problem of publication boom. The first effects of electronic publishing were appeared on the academic and scholarly publications then electronic publishing became a crucial part of all types of publications. As a result of these developments, collection developments and service policies of information centers were also significantly changed. In this article, after a general introduction about selection and evaluation processes of electronic publications, the subscribed databases by a state and a privately owned university in Turkey and their usage were examined. İkinci dünya savaşından sonra görülen yayın patlaması, basılı kaynakların denetim ve erişiminde sorunlar yaşanmasına neden olmuştur. Bu da yayıncılık sektöründe yeni arayışlara yol açmıştır. 1980’li yıllardan sonra basılı yayın fiyatlarındaki hızlı artış da bu etmenlere eklenince elektronik yayıncılık sektörü gelişmeye başlamıştır. Öncelikle bilimsel ve akademik yayınlarla başlayan elektronik yayın günümüzde tüm yayın türlerini kapsamaktadır. Yayıncılıktaki bu gelişim bilgi merkezlerinin derme geliştirme ve hizmet politikalarını da önemli ölçüde değiştirmiştir. Bu çalışmada elektronik yayınların seçim, değerlendirme ve sağlama konularında genel bir girişten sonra bir devlet üniversitesinin bir de özel üniversitenin abone olduğu veritabanları ve bu veri tabanlarının kullanımının değerlendirilmesi yapılmaktadır.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. Interaction between Mitochondrial Reactive Oxygen Species, Heme Oxygenase, and Nitric Oxide Synthase Stimulates Phagocytosis in Macrophages

    Directory of Open Access Journals (Sweden)

    Andrea Müllebner

    2018-01-01

    Full Text Available BackgroundMacrophages are cells of the innate immune system that populate every organ. They are required not only for defense against invading pathogens and tissue repair but also for maintenance of tissue homeostasis and iron homeostasis.AimThe aim of this study is to understand whether heme oxygenase (HO and nitric oxide synthase (NOS contribute to the regulation of nicotinamide adenine dinucleotide phosphate oxidase (NOX activity and phagocytosis, two key components of macrophage function.MethodsThis study was carried out using resting J774A.1 macrophages treated with hemin or vehicle. Activity of NOS, HO, or NOX was inhibited using specific inhibitors. Reactive oxygen species (ROS formation was determined by Amplex® red assay, and phagocytosis was measured using fluorescein isothiocyanate-labeled bacteria. In addition, we analyzed the fate of the intracellular heme by using electron spin resonance.ResultsWe show that both enzymes NOS and HO are essential for phagocytic activity of macrophages. NOS does not directly affect phagocytosis, but stimulates NOX activity via nitric oxide-triggered ROS production of mitochondria. Treatment of macrophages with hemin results in intracellular accumulation of ferrous heme and an inhibition of phagocytosis. In contrast to NOS, HO products, including carbon monoxide, neither clearly affect NOX activity nor clearly affect phagocytosis, but phagocytosis is accelerated by HO-mediated degradation of heme.ConclusionBoth enzymes contribute to the bactericidal activity of macrophages independently, by controlling different pathways.

  3. 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.

  4. SP-A binding sites on bovine alveolar macrophages.

    Science.gov (United States)

    Plaga, S; Plattner, H; Schlepper-Schaefer, J

    1998-11-25

    Surfactant protein A (SP-A) binding to bovine alveolar macrophages was examined in order to characterize SP-A binding proteins on the cell surface and to isolate putative receptors from these cells that could be obtained in large amounts. Human SP-A, unlabeled or labeled with gold particles, was bound to freshly isolated macrophages and analyzed with ELISA or the transmission electron microscope. Binding of SP-A was inhibited by Ca2+ chelation, by an excess of unlabeled SP-A, or by the presence of 20 mg/ml mannan. We conclude that bovine alveolar macrophages expose binding sites for SP-A that are specific and that depend on Ca2+ and on mannose residues. For isolation of SP-A receptors with homologous SP-A as ligand we isolated SP-A from bovine lung lavage. SDS-PAGE analysis of the purified SP-A showed a protein of 32-36 kDa. Functional integrity of the protein was demonstrated. Bovine SP-A bound to Dynabeads was used to isolate SP-A binding proteins. From the fractionated and blotted proteins of the receptor preparation two proteins bound SP-A in a Ca2+-dependent manner, a 40-kDa protein showing mannose dependency and a 210-kDa protein, showing no mannose sensitivity. Copyright 1998 Academic Press.

  5. 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

  6. Utility of the electronic information resource UpToDate for clinical decision-making at bedside rounds.

    Science.gov (United States)

    Phua, J; See, K C; Khalizah, H J; Low, S P; Lim, T K

    2012-02-01

    Clinical questions often arise at daily hospital bedside rounds. Yet, little information exists on how the search for answers may be facilitated. The aim of this prospective study was, therefore, to evaluate the overall utility, including the feasibility and usefulness of incorporating searches of UpToDate, a popular online information resource, into rounds. Doctors searched UpToDate for any unresolved clinical questions during rounds for patients in general medicine and respiratory wards, and in the medical intensive care unit of a tertiary teaching hospital. The nature of the questions and the results of the searches were recorded. Searches were deemed feasible if they were completed during the rounds and useful if they provided a satisfactory answer. A total of 157 UpToDate searches were performed during the study period. Questions were raised by all ranks of clinicians from junior doctors to consultants. The searches were feasible and performed immediately during rounds 44% of the time. Each search took a median of three minutes (first quartile: two minutes, third quartile: five minutes). UpToDate provided a useful and satisfactory answer 75% of the time, a partial answer 17% of the time and no answer 9% of the time. It led to a change in investigations, diagnosis or management 37% of the time, confirmed what was originally known or planned 38% of the time and had no effect 25% of the time. Incorporating UpToDate searches into daily bedside rounds was feasible and useful in clinical decision-making.

  7. Efficient internalization of mesoporous silica particles of different sizes by primary human macrophages without impairment of macrophage clearance of apoptotic or antibody-opsonized target cells

    International Nuclear Information System (INIS)

    Witasp, Erika; Kupferschmidt, Natalia; Bengtsson, Linnea; Hultenby, Kjell; Smedman, Christian; Paulie, Staffan; Garcia-Bennett, Alfonso E.; Fadeel, Bengt

    2009-01-01

    Macrophage recognition and ingestion of apoptotic cell corpses, a process referred to as programmed cell clearance, is of considerable importance for the maintenance of tissue homeostasis and in the resolution of inflammation. Moreover, macrophages are the first line of defense against microorganisms and other foreign materials including particles. However, there is sparse information on the mode of uptake of engineered nanomaterials by primary macrophages. In this study, mesoporous silica particles with cubic pore geometries and covalently fluorescein-grafted particles were synthesized through a novel route, and their interactions with primary human monocyte-derived macrophages were assessed. Efficient and active internalization of mesoporous silica particles of different sizes was observed by transmission electron microscopic and flow cytometric analysis and studies using pharmacological inhibitors suggested that uptake occurred through a process of endocytosis. Moreover, uptake of silica particles was independent of serum factors. The silica particles with very high surface areas due to their porous structure did not impair cell viability or function of macrophages, including the ingestion of different classes of apoptotic or opsonized target cells. The current findings are relevant to the development of mesoporous materials for drug delivery and other biomedical applications.

  8. Macrophage proinflammatory response to the titanium alloy equipment in dental implantation.

    Science.gov (United States)

    Chen, X; Li, H S; Yin, Y; Feng, Y; Tan, X W

    2015-08-07

    Titanium alloy and stainless steel (SS) had been widely used as dental implant materials because of their affinity with epithelial tissue and connective tissue, and good physical, chemical, biological, mechanical properties and processability. We compared the effects of titanium alloy and SS on macrophage cytokine expression as well as their biocompatibility. Mouse macrophage RAW264.7 cells were cultured on titanium alloy and SS surfaces. Cells were counted by scanning electron microscopy. A nitride oxide kit was used to detect released nitric oxide by macrophages on the different materials. An enzyme linked immunosorbent assay was used to detect monocyte chemoattractant protein-1 levels. Scanning electron microscopy revealed fewer macrophages on the surface of titanium alloy (48.2 ± 6.4 x 10(3) cells/cm(2)) than on SS (135 ± 7.3 x 10(3) cells/cm(2)). The nitric oxide content stimulated by titanium alloy was 22.5 mM, which was lower than that stimulated by SS (26.8 mM), but the difference was not statistically significant (P = 0.07). The level of monocyte chemoattractant protein-1 released was significantly higher in the SS group (OD value = 0.128) than in the titanium alloy group (OD value = 0.081) (P = 0.024). The transforming growth factor-b1 mRNA expression levels in macrophages after stimulation by titanium alloy for 12 and 36 h were significantly higher than that after stimulation by SS (P = 0.31 and 0.25, respectively). Macrophages participate in the inflammatory response by regulating cytokines such as nitric oxide, monocyte chemoattractant protein-1, and transforming growth factor-b1. There were fewer macrophages and lower inflammation on the titanium alloy surface than on the SS surface. Titanium alloy materials exhibited better biological compatibility than did SS.

  9. 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.

  10. 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.

  11. 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.

  12. Comprehensive evaluation of electronic medical record system use and user satisfaction at five low-resource setting hospitals in ethiopia.

    Science.gov (United States)

    Tilahun, Binyam; Fritz, Fleur

    2015-05-25

    Electronic medical record (EMR) systems are increasingly being implemented in hospitals of developing countries to improve patient care and clinical service. However, only limited evaluation studies are available concerning the level of adoption and determinant factors of success in those settings. The objective of this study was to assess the usage pattern, user satisfaction level, and determinants of health professional's satisfaction towards a comprehensive EMR system implemented in Ethiopia where parallel documentation using the EMR and the paper-based medical records is in practice. A quantitative, cross-sectional study design was used to assess the usage pattern, user satisfaction level, and determinant factors of an EMR system implemented in Ethiopia based on the DeLone and McLean model of information system success. Descriptive statistical methods were applied to analyze the data and a binary logistic regression model was used to identify determinant factors. Health professionals (N=422) from five hospitals were approached and 406 responded to the survey (96.2% response rate). Out of the respondents, 76.1% (309/406) started to use the system immediately after implementation and user training, but only 31.7% (98/309) of the professionals reported using the EMR during the study (after 3 years of implementation). Of the 12 core EMR functions, 3 were never used by most respondents, and they were also unaware of 4 of the core EMR functions. It was found that 61.4% (190/309) of the health professionals reported over all dissatisfaction with the EMR (median=4, interquartile range (IQR)=1) on a 5-level Likert scale. Physicians were more dissatisfied (median=5, IQR=1) when compared to nurses (median=4, IQR=1) and the health management information system (HMIS) staff (median=2, IQR=1). Of all the participants, 64.4% (199/309) believed that the EMR had no positive impact on the quality of care. The participants indicated an agreement with the system and information

  13. Gold nanorods as a theranostic platform for in vitro and in vivo imaging and photothermal therapy of inflammatory macrophages

    Science.gov (United States)

    Qin, Jinbao; Peng, Zhiyou; Li, Bo; Ye, Kaichuang; Zhang, Yuxin; Yuan, Fukang; Yang, Xinrui; Huang, Lijia; Hu, Junqing; Lu, Xinwu

    2015-08-01

    Inflammatory macrophages play pivotal roles in the development of atherosclerosis. Theranostics, a promising approach for local imaging and photothermal therapy of inflammatory macrophages, has drawn increasing attention in biomedical research. In this study, gold nanorods (Au NRs) were synthesized, and their in vitro photothermal effects on the macrophage cell line (Ana-1 cells) under 808 nm near infrared reflection (NIR) were investigated by the CCK8 assay, calcein AM/PI staining, flow cytometry, transmission electron microscopy (TEM), silver staining and in vitro micro-computed tomography (CT) imaging. These Au NRs were then applied to an apolipoprotein E knockout (Apo E) mouse model to evaluate their effects on in vivo CT imaging and their effectiveness as for the subsequent photothermal therapy of macrophages in femoral artery restenosis under 808 nm laser irradiation. In vitro photothermal ablation treatment using Au NRs exhibited a significant cell-killing efficacy of macrophages, even at relatively low concentrations of Au NRs and low NIR powers. In addition, the in vivo results demonstrated that the Au NRs are effective for in vivo imaging and photothermal therapy of inflammatory macrophages in femoral artery restenosis. This study shows that Au nanorods are a promising theranostic platform for the diagnosis and photothermal therapy of inflammation-associated diseases.Inflammatory macrophages play pivotal roles in the development of atherosclerosis. Theranostics, a promising approach for local imaging and photothermal therapy of inflammatory macrophages, has drawn increasing attention in biomedical research. In this study, gold nanorods (Au NRs) were synthesized, and their in vitro photothermal effects on the macrophage cell line (Ana-1 cells) under 808 nm near infrared reflection (NIR) were investigated by the CCK8 assay, calcein AM/PI staining, flow cytometry, transmission electron microscopy (TEM), silver staining and in vitro micro-computed tomography

  14. 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.

  15. 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...

  16. Tracking bacterial infection of macrophages using a novel red-emission pH sensor.

    Science.gov (United States)

    Jin, Yuguang; Tian, Yanqing; Zhang, Weiwen; Jang, Sei-Hum; Jen, Alex K-Y; Meldrum, Deirdre R

    2010-10-01

    The relationship between bacteria and host phagocytic cells is key to the induction of immunity. To visualize and monitor bacterial infection, we developed a novel bacterial membrane permeable pH sensor for the noninvasive monitoring of bacterial entry into murine macrophages. The pH sensor was constructed using 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) as an electron-withdrawing group and aniline as an electron-donating group. A piperazine moiety was used as the pH-sensitive group. Because of the strong electron-donating and -withdrawing units conjugated in the sensing moiety M, the fluorophore emitted in the red spectral window, away from the autofluorescence regions of the bacteria. Following the engulfment of sensor-labeled bacteria by macrophages and their subsequent merger with host lysosomes, the resulting low-pH environment enhances the fluorescence intensity of the pH sensors inside the bacteria. Time-lapse analysis of the fluorescent intensity suggested significant heterogeneity of bacterial uptake among macrophages. In addition, qRT-PCR analysis of the bacterial 16 S rRNA gene expression within single macrophage cells suggested that the 16 S rRNA of the bacteria was still intact 120 min after they had been engulfed by macrophages. A toxicity assay showed that the pH sensor has no cytotoxicity towards either E. coli or murine macrophages. The sensor shows good repeatability, a long lifetime, and a fast response to pH changes, and can be used for a variety of bacteria.

  17. Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures.

    Science.gov (United States)

    Fernandes, Maria Cecilia; Dillon, Laura A L; Belew, Ashton Trey; Bravo, Hector Corrada; Mosser, David M; El-Sayed, Najib M

    2016-05-10

    infection that was reduced at later time points. A similar expression pattern was observed in the parasites. Our analyses provide specific insights into the interplay between human macrophages and Leishmania parasites and constitute an important general resource for the study of how pathogens evade host defenses and modulate the functions of the cell to survive intracellularly. Copyright © 2016 Fernandes et al.

  18. Randomized Controlled Trial of Electronic Care Plan Alerts and Resource Utilization by High Frequency Emergency Department Users with Opioid Use Disorder

    Directory of Open Access Journals (Sweden)

    Niels Rathlev, MD

    2016-01-01

    Full Text Available Introduction: There is a paucity of literature supporting the use of electronic alerts for patients with high frequency emergency department (ED use. We sought to measure changes in opioid prescribing and administration practices, total charges and other resource utilization using electronic alerts to notify providers of an opioid-use care plan for high frequency ED patients. Methods: This was a randomized, non-blinded, two-group parallel design study of patients who had 1 opioid use disorder and 2 high frequency ED use. Three affiliated hospitals with identical electronic health records participated. Patients were randomized into “Care Plan” versus “Usual Care groups”. Between the years before and after randomization, we compared as primary outcomes the following: 1 opioids (morphine mg equivalents prescribed to patients upon discharge and administered to ED and inpatients; 2 total medical charges, and the numbers of; 3 ED visits, 4 ED visits with advanced radiologic imaging (computed tomography [CT] or magnetic resonance imaging [MRI] studies, and 5 inpatient admissions. Results: A total of 40 patients were enrolled. For ED and inpatients in the “Usual Care” group, the proportion of morphine mg equivalents received in the post-period compared with the pre-period was 15.7%, while in the “Care Plan” group the proportion received in the post-period compared with the pre-period was 4.5% (ratio=0.29, 95% CI [0.07-1.12]; p=0.07. For discharged patients in the “Usual Care” group, the proportion of morphine mg equivalents prescribed in the post-period compared with the pre-period was 25.7% while in the “Care Plan” group, the proportion prescribed in the post-period compared to the pre-period was 2.9%. The “Care Plan” group showed an 89% greater proportional change over the periods compared with the “Usual Care” group (ratio=0.11, 95% CI [0.01-0.092]; p=0.04. Care plans did not change the total charges, or, the numbers

  19. 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.

  20. 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.

  1. 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

  2. There is a Relationship between Resource Expenditures and Reference Transactions in Academic Libraries. A Review of: Dubnjakovic, A. (2012. Electronic resource expenditure and the decline in reference transaction statistics in academic libraries. Journal of Academic Librarianship, 38(2, 94-100. doi:10.1016/j.acalib.2012.01.001

    Directory of Open Access Journals (Sweden)

    Annie M. Hughes

    2013-03-01

    Full Text Available Objective – To provide an analysis of the impact of expenditures on electronic resourcesand gate counts on the increase or decrease in reference transactions.Design – Analysis of results of existing survey data from the National Center for Educational Statistics (NCES 2006 Academic Library Survey(ALS.Setting – Academic libraries in the United States.Subjects – 3925 academic library respondents.Methods – The author chose to use survey data collected from the 2006 ALS conducted bythe NCES. The survey included data on various topics related to academic libraries, but in the case of this study, the author chose to analyze three of the 193 variables included. The three variables: electronic books expenditure, computer hardware and software, and expenditures on bibliographic utilities, were combined into one variable called electronic resource expenditure. Gate counts were also considered as a variable. Electronic resource expenditure was also split as a variable into three groups: low, medium, and high. Multiple regression analysis and general linear modeling, along with tests of reliability, were employed. Main Results – The author determined that low, medium, and high spenders with regard to electronic resources exhibited differences in gate counts, and gate counts have an effect on reference transactions in any given week. Gate counts tend to not have much of an effect on reference transactions for the higher spenders, and higher spenders tend to have a higher number of reference transactions overall. Low spenders have lower gate counts and also a lower amount of reference transactions.Conclusion – The findings from this study show that academic libraries spending more on electronic resources also tend to have an increase with regard to reference transactions. The author also concludes that library spaces are no longer the determining factor with regard to number of reference transactions. Spending more on electronic resources is

  3. 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.

  4. Global application of disorders of sex development-related electronic resources: e-learning, e-consultation and e-information sharing.

    Science.gov (United States)

    Muscarella, Miriam; Kranenburg-van Koppen, Laura; Grijpink-van den Biggelaar, Kalinka; Drop, Stenvert L S

    2014-01-01

    The past 20 years have seen proliferation of electronic (e) resources that promote improved understanding of disorders of sex development (DSD): e-learning for physicians and trainees, e-consultation between clinicians, and e-information for families and affected individuals. Recent e-learning advances have emerged from the European Society for Pediatric Endocrinology's online learning portal for current physicians and trainees. Developed with attention to developing clinical competencies incorporating learning theory, and presenting material that represents international best practice, this e-learning portal offers advances in training, making information more accessible for clinicians and trainees. Multiple levels of instruction, authentic case examples, collaborative forums for physicians and trainees, individualized feedback and user-friendly tools represent advances in trainee and physician learning that can take place in any location. e-consultation is an emerging tool that aims to connect physicians with specialists experienced in DSD care. Although it faces logistical challenges, e-consultation carries the potential to improve DSD care, especially in remote areas with limited access to DSD specialists. e-information for families and patients of all ages is widely accessible online, often with focus on DSD biology, medical care, and psychological and social support. e-information tools aid self-management and support of those affected by DSD. Efforts to improve these resources should aim to map information to individual users, incorporate optimally clear nomenclature, and continue as a 'shared enterprise' of clinicians, affected individuals, families and researchers. Improving the quality of DSD-related e-learning and e-information and developing e-consultation carries the potential to transform DSD care and support for patients, families and physicians worldwide. © 2014 S. Karger AG, Basel.

  5. 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.

  6. Tracking bacterial infection into macrophages by a novel red-emission pH sensor

    OpenAIRE

    Jin, Yuguang; Tian, Yanqing; Zhang, Weiwen; Jang, Sei-Hum; Jen, Alex K.-Y.; Meldrum, Deirdre R.

    2010-01-01

    The relationship between bacteria and host phagocytic cells is a key to the induction of immunity. To visualize and monitor bacterial infection, we developed a novel bacterial membrane permeable pH sensor for noninvasive monitoring of bacterial entry into murine macrophages. The pH sensor was constructed using 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) as an electron-withdrawing group and aniline as an electron donating group. A piperazine moiety was u...

  7. 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

  8. 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.

  9. 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.

  10. Ranking Medical Terms to Support Expansion of Lay Language Resources for Patient Comprehension of Electronic Health Record Notes: Adapted Distant Supervision Approach.

    Science.gov (United States)

    Chen, Jinying; Jagannatha, Abhyuday N; Fodeh, Samah J; Yu, Hong

    2017-10-31

    Medical terms are a major obstacle for patients to comprehend their electronic health record (EHR) notes. Clinical natural language processing (NLP) systems that link EHR terms to lay terms or definitions allow patients to easily access helpful information when reading through their EHR notes, and have shown to improve patient EHR comprehension. However, high-quality lay language resources for EHR terms are very limited in the public domain. Because expanding and curating such a resource is a costly process, it is beneficial and even necessary to identify terms important for patient EHR comprehension first. We aimed to develop an NLP system, called adapted distant supervision (ADS), to rank candidate terms mined from EHR corpora. We will give EHR terms ranked as high by ADS a higher priority for lay language annotation-that is, creating lay definitions for these terms. Adapted distant supervision uses distant supervision from consumer health vocabulary and transfer learning to adapt itself to solve the problem of ranking EHR terms in the target domain. We investigated 2 state-of-the-art transfer learning algorithms (ie, feature space augmentation and supervised distant supervision) and designed 5 types of learning features, including distributed word representations learned from large EHR data for ADS. For evaluating ADS, we asked domain experts to annotate 6038 candidate terms as important or nonimportant for EHR comprehension. We then randomly divided these data into the target-domain training data (1000 examples) and the evaluation data (5038 examples). We compared ADS with 2 strong baselines, including standard supervised learning, on the evaluation data. The ADS system using feature space augmentation achieved the best average precision, 0.850, on the evaluation set when using 1000 target-domain training examples. The ADS system using supervised distant supervision achieved the best average precision, 0.819, on the evaluation set when using only 100 target

  11. Modulation of allogeneic stimulation in man. I. Characterization of an in vitro induced suppressor macrophage population

    International Nuclear Information System (INIS)

    Stux, S.V.; Dubey, D.P.; Yunis, E.J.

    1981-01-01

    Cultured human peripheral blood mononuclear cells suppressed the allogeneic response of fresh autologous lymphocytes. This suppressor activity developed gradually over a period of one week. The cells primarily responsible for this effect were enriched by Ficoll density gradient centrifugation. It was found that the suppressor cell is a large, low density nylon wool adherent, radioresistant, phagocytic, and nonspecific esterase positive mononuclear cell. Moreover, these cells did not form E rosettes and were Fc positive. Electron microscopy confirmed that suppressor cells were macrophage like. Suppressor activity was not due to cytotoxicity, crowding, or steric hinderance by the cultured cells. The suppressor macrophage population did not appear to inhibit the allogeneic response via prostaglandin or arginase release, or interfere with the tritiated thymidine uptake by release of endogenous thymidine. The above system is viewed as an in vitro model of immune regulation by suppressor macrophages, in the context of allogeneic response

  12. In vitro photodynamic effects of scavenger receptor targeted-photoactivatable nanoagents on activated macrophages.

    Science.gov (United States)

    Yi, Bong Gu; Park, Ok Kyu; Jeong, Myeong Seon; Kwon, Seung Hae; Jung, Jae In; Lee, Seongsoo; Ryoo, Sungwoo; Kim, Sung Eun; Kim, Jin Won; Moon, Won-Jin; Park, Kyeongsoon

    2017-04-01

    Scavenger receptors (SRs) expressed on the activated macrophages in inflammation sites have been considered as the most interesting and important target biomarker for targeted drug delivery, imaging and therapy. In the present study, we fabricated the scavenger receptor-A (SR-A) targeted-photoactivatable nanoagents (termed as Ce6/DS-DOCA) by entrapping chlorin e6 (Ce6) into the amphiphilic dextran sulfate-deoxycholic acid (DS-DOCA) conjugates via physically hydrophobic interactions. Insoluble Ce6 was easily encapsulated into DS-DOCA nanoparticles by a dialysis method and the loading efficiency was approximately 51.7%. The Ce6/DS-DOCA formed nano-sized self-assembled aggregates (28.8±5.6nm in diameter), confirmed by transmission electron microscope, UV/Vis and fluorescence spectrophotometer. The Ce6/DS-DOCA nanoagents could generate highly reactive singlet oxygen under laser irradiation. Also, in vitro studies showed that they were more specifically taken up by lipopolysaccharide (LPS)-induced activated macrophages (RAW 264.7) via a SR-A-mediated endocytosis, relative to by non-activated macrophages, and notably induced cell death of activated macrophages under laser irradiation. Therefore, SR-A targetable and photoactivatable Ce6/DS-DOCA nanoagents with more selective targeting to the activated macrophages will have great potential for treatment of inflammatory diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

    Directory of Open Access Journals (Sweden)

    Juan Lin

    2013-01-01

    Full Text Available Necrotic death of macrophages has long been known to be present in atherosclerotic lesions but has not been studied. We examined the role of receptor interacting protein (RIP 3, a mediator of necrotic cell death, in atherosclerosis and found that RIP3−/−;Ldlr−/− mice were no different from RIP3+/+;Ldlr−/− mice in early atherosclerosis but had significant reduction in advanced atherosclerotic lesions. Similar results were observed in Apoe−/− background mice. Bone marrow transplantation revealed that loss of RIP3 expression from bone-marrow-derived cells is responsible for the reduced disease progression. While no difference was found in apoptosis between RIP3−/−;Ldlr−/− and RIP3+/+;Ldlr−/− mice, electron microscopy revealed a significant reduction of macrophage primary necrosis in the advanced lesions of RIP3−/− mice. In vitro cellular studies showed that RIP3 deletion had no effect on oxidized low-density lipoprotein (LDL-induced macrophage apoptosis, but prevented macrophage primary necrosis occurring in response to oxidized LDL under caspase inhibition or RIP3 overexpression conditions. RIP3-dependent necrosis is not postapoptotic, and the increased primary necrosis in advanced atherosclerotic lesions most likely resulted from the increase of RIP3 expression. Our data demonstrate that primary necrosis of macrophages is proatherogenic during advanced atherosclerosis development.

  14. Impact of two interventions on timeliness and data quality of an electronic disease surveillance system in a resource limited setting (Peru: a prospective evaluation

    Directory of Open Access Journals (Sweden)

    Quispe Jose A

    2009-03-01

    Full Text Available Abstract Background A timely detection of outbreaks through surveillance is needed in order to prevent future pandemics. However, current surveillance systems may not be prepared to accomplish this goal, especially in resource limited settings. As data quality and timeliness are attributes that improve outbreak detection capacity, we assessed the effect of two interventions on such attributes in Alerta, an electronic disease surveillance system in the Peruvian Navy. Methods 40 Alerta reporting units (18 clinics and 22 ships were included in a 12-week prospective evaluation project. After a short refresher course on the notification process, units were randomly assigned to either a phone, visit or control group. Phone group sites were called three hours before the biweekly reporting deadline if they had not sent their report. Visit group sites received supervision visits on weeks 4 & 8, but no phone calls. The control group sites were not contacted by phone or visited. Timeliness and data quality were assessed by calculating the percentage of reports sent on time and percentage of errors per total number of reports, respectively. Results Timeliness improved in the phone group from 64.6% to 84% in clinics (+19.4 [95% CI, +10.3 to +28.6]; p Conclusion Regular phone reminders significantly improved timeliness of reports in clinics and ships, whereas supervision visits led to improved data quality only among clinics. Further investigations are needed to establish the cost-effectiveness and optimal use of each of these strategies.

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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...

  2. 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.

  3. Online Resources

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Online Resources. Journal of Genetics. Online Resources. Volume 97. 2018 | Online resources. Volume 96. 2017 | Online resources. Volume 95. 2016 | Online resources. Volume 94. 2015 | Online resources. Volume 93. 2014 | Online resources. Volume 92. 2013 | Online resources ...

  4. 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

  5. Interactive Electronic Decision Trees for the Integrated Primary Care Management of Febrile Children in Low Resource Settings - Review of existing tools.

    Science.gov (United States)

    Keitel, Kristina; D'Acremont, Valérie

    2018-04-20

    The lack of effective, integrated diagnostic tools pose a major challenge to the primary care management of febrile childhood illnesses. These limitations are especially evident in low-resource settings and are often inappropriately compensated by antimicrobial over-prescription. Interactive electronic decision trees (IEDTs) have the potential to close these gaps: guiding antibiotic use and better identifying serious disease. This narrative review summarizes existing IEDTs, to provide an overview of their degree of validation, as well as to identify gaps in current knowledge and prospects for future innovation. Structured literature review in PubMed and Embase complemented by google search and contact with developers. Six integrated IEDTs were identified: three (eIMCI, REC, and Bangladesh digital IMCI) based on Integrated Management of Childhood Illnesses (IMCI); four (SL eCCM, MEDSINC, e-iCCM, and D-Tree eCCM) on Integrated Community Case Management (iCCM); two (ALMANACH, MSFeCARE) with a modified IMCI content; and one (ePOCT) that integrates novel content with biomarker testing. The types of publications and evaluation studies varied greatly: the content and evidence-base was published for two (ALMANACH and ePOCT), ALMANACH and ePOCT were validated in efficacy studies. Other types of evaluations, such as compliance, acceptability were available for D-Tree eCCM, eIMCI, ALMANACH. Several evaluations are still ongoing. Future prospects include conducting effectiveness and impact studies using data gathered through larger studies to adapt the medical content to local epidemiology, improving the software and sensors, and Assessing factors that influence compliance and scale-up. IEDTs are valuable tools that have the potential to improve management of febrile children in primary care and increase the rational use of diagnostics and antimicrobials. Next steps in the evidence pathway should be larger effectiveness and impact studies (including cost analysis) and

  6. Efferocytosis is impaired in Gaucher macrophages.

    Science.gov (United States)

    Aflaki, Elma; Borger, Daniel K; Grey, Richard J; Kirby, Martha; Anderson, Stacie; Lopez, Grisel; Sidransky, Ellen

    2017-04-01

    Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, is characterized by the presence of glucosylceramide-laden macrophages resulting from impaired digestion of aged erythrocytes or apoptotic leukocytes. Studies of macrophages from patients with type 1 Gaucher disease with genotypes N370S/N370S, N370S/L444P or N370S/c.84dupG revealed that Gaucher macrophages have impaired efferocytosis resulting from reduced levels of p67 phox and Rab7. The decreased Rab7 expression leads to impaired fusion of phagosomes with lysosomes. Moreover, there is defective translocation of p67 phox to phagosomes, resulting in reduced intracellular production of reactive oxygen species. These factors contribute to defective deposition and clearance of apoptotic cells in phagolysosomes, which may have an impact on the inflammatory response and contribute to the organomegaly and inflammation seen in patients with Gaucher disease. Copyright© Ferrata Storti Foundation.

  7. Lysine Deacetylases and Regulated Glycolysis in Macrophages.

    Science.gov (United States)

    Shakespear, Melanie R; Iyer, Abishek; Cheng, Catherine Youting; Das Gupta, Kaustav; Singhal, Amit; Fairlie, David P; Sweet, Matthew J

    2018-06-01

    Regulated cellular metabolism has emerged as a fundamental process controlling macrophage functions, but there is still much to uncover about the precise signaling mechanisms involved. Lysine acetylation regulates the activity, stability, and/or localization of metabolic enzymes, as well as inflammatory responses, in macrophages. Two protein families, the classical zinc-dependent histone deacetylases (HDACs) and the NAD-dependent HDACs (sirtuins, SIRTs), mediate lysine deacetylation. We describe here mechanisms by which classical HDACs and SIRTs directly regulate specific glycolytic enzymes, as well as evidence that links these protein deacetylases to the regulation of glycolysis-related genes. In these contexts, we discuss HDACs and SIRTs as key control points for regulating immunometabolism and inflammatory outputs from macrophages. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Adipocyte fetuin-A contributes to macrophage migration into adipose tissue and polarization of macrophages.

    Science.gov (United States)

    Chatterjee, Priyajit; Seal, Soma; Mukherjee, Sandip; Kundu, Rakesh; Mukherjee, Sutapa; Ray, Sukanta; Mukhopadhyay, Satinath; Majumdar, Subeer S; Bhattacharya, Samir

    2013-09-27

    Macrophage infiltration into adipose tissue during obesity and their phenotypic conversion from anti-inflammatory M2 to proinflammatory M1 subtype significantly contributes to develop a link between inflammation and insulin resistance; signaling molecule(s) for these events, however, remains poorly understood. We demonstrate here that excess lipid in the adipose tissue environment may trigger one such signal. Adipose tissue from obese diabetic db/db mice, high fat diet-fed mice, and obese diabetic patients showed significantly elevated fetuin-A (FetA) levels in respect to their controls; partially hepatectomized high fat diet mice did not show noticeable alteration, indicating adipose tissue to be the source of this alteration. In adipocytes, fatty acid induces FetA gene and protein expressions, resulting in its copious release. We found that FetA could act as a chemoattractant for macrophages. To simulate lipid-induced inflammatory conditions when proinflammatory adipose tissue and macrophages create a niche of an altered microenvironment, we set up a transculture system of macrophages and adipocytes; the addition of fatty acid to adipocytes released FetA into the medium, which polarized M2 macrophages to M1. This was further confirmed by direct FetA addition to macrophages. Taken together, lipid-induced FetA from adipocytes is an efficient chemokine for macrophage migration and polarization. These findings open a new dimension for understanding obesity-induced inflammation.

  9. Drug Trafficking into Macrophages via the Endocytotic Receptor CD163

    DEFF Research Database (Denmark)

    Graversen, Jonas Heilskov; Moestrup, Søren Kragh

    2015-01-01

    for cytotoxic or phenotype-modulating drugs in the treatment of inflammatory and cancerous diseases. Such targeting of macrophages has been tried using the natural propensity of macrophages to non-specifically phagocytose circulating foreign particulate material. In addition, the specific targeting...... of macrophage-expressed receptors has been used in order to obtain a selective uptake in macrophages and reduce adverse effects of off-target delivery of drugs. CD163 is a highly expressed macrophage-specific endocytic receptor that has been studied for intracellular delivery of small molecule drugs...... to macrophages using targeted liposomes or antibody drug conjugates. This review will focus on the biology of CD163 and its potential role as a target for selective macrophage targeting compared with other macrophage targeting approaches....

  10. 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...

  11. 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.

  12. The macrophage scavenger receptor CD163

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Madsen, Mette; Møller, Holger J

    2006-01-01

    CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants are subs......CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants...

  13. Library resources on the Internet

    Science.gov (United States)

    Buchanan, Nancy L.

    1995-07-01

    Library resources are prevalent on the Internet. Library catalogs, electronic books, electronic periodicals, periodical indexes, reference sources, and U.S. Government documents are available by telnet, Gopher, World Wide Web, and FTP. Comparatively few copyrighted library resources are available freely on the Internet. Internet implementations of library resources can add useful features, such as full-text searching. There are discussion lists, Gophers, and World Wide Web pages to help users keep up with new resources and changes to existing ones. The future will bring more library resources, more types of library resources, and more integrated implementations of such resources to the Internet.

  14. Noninvasive detection of macrophages in atherosclerotic lesions by computed tomography enhanced with PEGylated gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Qin J

    2014-12-01

    Full Text Available Jinbao Qin,1,* Chen Peng,2,* Binghui Zhao,2,* Kaichuang Ye,1 Fukang Yuan,1 Zhiyou Peng,1 Xinrui Yang,1 Lijia Huang,1 Mier Jiang,1 Qinghua Zhao,3 Guangyu Tang,2 Xinwu Lu1,4 1Department of Vascular Surgery, Shanghai Ninth People’s Hospital Affiliated to Shanghai JiaoTong University, School of Medicine; 2Department of Radiology, Shanghai Tenth People’s Hospital Affiliated to Tongji University, School of Medicine; 3Department of Orthopaedics, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University; 4Vascular Center of Shanghai JiaoTong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Macrophages are becoming increasingly significant in the progression of atherosclerosis (AS. Molecular imaging of macrophages may improve the detection and characterization of AS. In this study, dendrimer-entrapped gold nanoparticles (Au DENPs with polyethylene glycol (PEG and fluorescein isothiocyanate (FI coatings were designed, tested, and applied as contrast agents for the enhanced computed tomography (CT imaging of macrophages in atherosclerotic lesions. Cell counting kit-8 assay, fluorescence microscopy, silver staining, and transmission electron microscopy revealed that the FI-functionalized Au DENPs are noncytotoxic at high concentrations (3.0 µM and can be efficiently taken up by murine macrophages in vitro. These nanoparticles were administered to apolipoprotein E knockout mice as AS models, which demonstrated that the macrophage burden in atherosclerotic areas can be tracked noninvasively and dynamically three-dimensionally in live animals using micro-CT. Our findings suggest that the designed PEGylated gold nanoparticles are promising biocompatible nanoprobes for the CT imaging of macrophages in atherosclerotic lesions and will provide new insights into the pathophysiology of AS and other concerned inflammatory diseases. Keywords: atherosclerosis, CT, in vivo

  15. Entrance and Survival of Brucella pinnipedialis Hooded Seal Strain in Human Macrophages and Epithelial Cells

    Science.gov (United States)

    Briquemont, Benjamin; Sørensen, Karen K.; Godfroid, Jacques

    2013-01-01

    Marine mammal Brucella spp. have been isolated from pinnipeds (B. pinnipedialis) and cetaceans (B. ceti) from around the world. Although the zoonotic potential of marine mammal brucellae is largely unknown, reports of human disease exist. There are few studies of the mechanisms of bacterial intracellular invasion and multiplication involving the marine mammal Brucella spp. We examined the infective capacity of two genetically different B. pinnipedialis strains (reference strain; NTCT 12890 and a hooded seal isolate; B17) by measuring the ability of the bacteria to enter and replicate in cultured phagocytes and epithelial cells. Human macrophage-like cells (THP-1), two murine macrophage cell lines (RAW264.7 and J774A.1), and a human malignant epithelial cell line (HeLa S3) were challenged with bacteria in a gentamicin protection assay. Our results show that B. pinnipedialis is internalized, but is then gradually eliminated during the next 72 – 96 hours. Confocal microscopy revealed that intracellular B. pinnipedialis hooded seal strain colocalized with lysosomal compartments at 1.5 and 24 hours after infection. Intracellular presence of B. pinnipedialis hooded seal strain was verified by transmission electron microscopy. By using a cholesterol-scavenging lipid inhibitor, entrance of B. pinnipedialis hooded seal strain in human macrophages was significantly reduced by 65.8 % (± 17.3), suggesting involvement of lipid-rafts in intracellular entry. Murine macrophages invaded by B. pinnipedialis do not release nitric oxide (NO) and intracellular bacterial presence does not induce cell death. In summary, B. pinnipedialis hooded seal strain can enter human and murine macrophages, as well as human epithelial cells. Intracellular entry of B. pinnipedialis hooded seal strain involves, but seems not to be limited to, lipid-rafts in human macrophages. Brucella pinnipedialis does not multiply or survive for prolonged periods intracellulary. PMID:24376851

  16. Azurophil granule proteins constitute the major mycobactericidal proteins in human neutrophils and enhance the killing of mycobacteria in macrophages.

    Directory of Open Access Journals (Sweden)

    Prajna Jena

    Full Text Available Pathogenic mycobacteria reside in, and are in turn controlled by, macrophages. However, emerging data suggest that neutrophils also play a critical role in innate immunity to tuberculosis, presumably by their different antibacterial granule proteins. In this study, we purified neutrophil azurophil and specific granules and systematically analyzed the antimycobacterial activity of some purified azurophil and specific granule proteins against M. smegmatis, M. bovis-BCG and M. tuberculosis H37Rv. Using gel overlay and colony forming unit assays we showed that the defensin-depleted azurophil granule proteins (AZP were more active against mycobacteria compared to other granule proteins and cytosolic proteins. The proteins showing antimycobacterial activity were identified by MALDI-TOF mass spectrometry. Electron microscopic studies demonstrate that the AZP disintegrate bacterial cell membrane resulting in killing of mycobacteria. Exogenous addition of AZP to murine macrophage RAW 264.7, THP-1 and peripheral blood monocyte-derived macrophages significantly reduced the intracellular survival of mycobacteria without exhibiting cytotoxic activity on macrophages. Immunofluorescence studies showed that macrophages actively endocytose neutrophil granular proteins. Treatment with AZP resulted in increase in co-localization of BCG containing phagosomes with lysosomes but not in increase of autophagy. These data demonstrate that neutrophil azurophil proteins may play an important role in controlling intracellular survival of mycobacteria in macrophages.

  17. Studies on the binding and transport processes of americium-241 hydroxide polymers in rat lung and bovine alveolar macrophages

    International Nuclear Information System (INIS)

    Taya, A.

    1986-03-01

    The binding of Am-241 hydroxide polymers to the cell components of rat lung was investigated using differential centrifugation, density gradient centrifugation with different media, gel chromatography, free flow electrophoresis and electron microscopic autoradiography with Pu-241. The bovine alveolar macrophage cultures were introduced as an in vitro test system for Am-241 uptake. Form the biochemical and electron microscopic studies it can be concluded that Am-241 is taken up by pulmonary macrophages, where its first storage site is probably the lysosome. Then the Am-241 seems to be solubilized in the lysosomes and to be bound to the cytosolic ferritin of macrophages. Am-241 might be released from the cells and crosses the alveolar membranes as bound to transferrin or as low molecular weight form. (orig.) [de

  18. Herpes - resources

    Science.gov (United States)

    Genital herpes - resources; Resources - genital herpes ... following organizations are good resources for information on genital herpes : March of Dimes -- www.marchofdimes.org/complications/sexually- ...

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

    Directory of Open Access Journals (Sweden)

    Marie Duhamel

    2016-06-01

    Full Text Available 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.

  20. Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages.

    Science.gov (United States)

    Soldano, Stefano; Pizzorni, Carmen; Paolino, Sabrina; Trombetta, Amelia Chiara; Montagna, Paola; Brizzolara, Renata; Ruaro, Barbara; Sulli, Alberto; Cutolo, Maurizio

    2016-01-01

    Alternatively activated (M2) macrophages are phenotypically characterized by the expression of specific markers, mainly macrophage scavenger receptors (CD204 and CD163) and mannose receptor-1 (CD206), and participate in the fibrotic process by over-producing pro-fibrotic molecules, such as transforming growth factor-beta1 (TGFbeta1) and metalloproteinase (MMP)-9. Endothelin-1 (ET-1) is implicated in the fibrotic process, exerting its pro-fibrotic effects through the interaction with its receptors (ETA and ETB). The study investigated the possible role of ET-1 in inducing the transition from cultured human macrophages into M2 cells. Cultured human monocytes (THP-1 cell line) were activated into macrophages (M0 macrophages) with phorbol myristate acetate and subsequently maintained in growth medium (M0-controls) or treated with either ET-1 (100nM) or interleukin-4 (IL-4, 10ng/mL, M2 inducer) for 72 hours. Similarly, primary cultures of human peripheral blood monocyte (PBM)-derived macrophages obtained from healthy subjects, were maintained in growth medium (untreated cells) or treated with ET-1 or IL-4 for 6 days. Both M0 and PBM-derived macrophages were pre-treated with ET receptor antagonist (ETA/BRA, bosentan 10-5M) for 1 hour before ET-1 stimulation. Protein and gene expression of CD204, CD206, CD163, TGFbeta1 were analysed by immunocytochemistry, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Gene expression of interleukin(IL)-10 and macrophage derived chemokine (CCL-22) was evaluated by qRT-PCR. MMP-9 production was investigated by gel zymography. ET-1 significantly increased the expression of M2 phenotype markers CD204, CD206, CD163, IL-10 and CCL-22, and the production of MMP-9 in both cultures of M0 and PBM-derived macrophages compared to M0-controls and untreated cells. In cultured PBM-derived macrophages, ET-1 increased TGFbeta1 protein and gene expression compared to untreated cells. The ET-1-mediated effects were

  1. Misbehaving macrophages in the pathogenesis of psoriasis.

    Science.gov (United States)

    Clark, Rachael A; Kupper, Thomas S

    2006-08-01

    Psoriasis is a chronic inflammatory skin disease unique to humans. In this issue of the JCI, 2 studies of very different mouse models of psoriasis both report that macrophages play a key role in inducing psoriasis-like skin disease. Psoriasis is clearly a polygenic, inherited disease of uncontrolled cutaneous inflammation. The debate that currently rages in the field is whether psoriasis is a disease of autoreactive T cells or whether it reflects an intrinsic defect within the skin--or both. However, these questions have proven difficult to dissect using molecular genetic tools. In the current studies, the authors have used 2 different animal models to address the role of macrophages in disease pathogenesis: Wang et al. use a mouse model in which inflammation is T cell dependent, whereas the model used by Stratis et al. is T cell independent (see the related articles beginning on pages 2105 and 2094, respectively). Strikingly, both groups report an important contribution by macrophages, implying that macrophages can contribute to both epithelial-based and T cell-mediated pathways of inflammation.

  2. Metabolic-epigenetic crosstalk in macrophage activation

    NARCIS (Netherlands)

    Baardman, Jeroen; Licht, Iris; de Winther, Menno P. J.; van den Bossche, Jan

    2015-01-01

    Epigenetic enzymes are emerging as crucial controllers of macrophages, innate immune cells that determine the outcome of many inflammatory diseases. Recent studies demonstrate that the activity of particular chromatin-modifying enzymes is regulated by the availability of specific metabolites like

  3. The macrophage scavenger receptor CD163

    NARCIS (Netherlands)

    Fabriek, Babs O.; Dijkstra, Christine D.; van den Berg, Timo K.

    2005-01-01

    Mature tissue macrophages form a first line of defense to recognize and eliminate potential pathogens; these specialized cells are capable of phagocytosis, degradation of self and foreign materials, establishment of cell-cell interactions, and the production of inflammatory mediators. Mature tissue

  4. Mouse adenovirus type 1 infection of macrophages

    NARCIS (Netherlands)

    Ashley, S.L.; Welton, A.R.; Harwood, K.M.; Rooijen, van N.; Spindler, K.R.

    2009-01-01

    Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. MAV-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus.

  5. NFAT5-Regulated Macrophage Polarization Supports the Proinflammatory Function of Macrophages and T Lymphocytes.

    Science.gov (United States)

    Tellechea, Mónica; Buxadé, Maria; Tejedor, Sonia; Aramburu, Jose; López-Rodríguez, Cristina

    2018-01-01

    Macrophages are exquisite sensors of tissue homeostasis that can rapidly switch between pro- and anti-inflammatory or regulatory modes to respond to perturbations in their microenvironment. This functional plasticity involves a precise orchestration of gene expression patterns whose transcriptional regulators have not been fully characterized. We had previously identified the transcription factor NFAT5 as an activator of TLR-induced responses, and in this study we explore its contribution to macrophage functions in different polarization settings. We found that both in classically and alternatively polarized macrophages, NFAT5 enhanced functions associated with a proinflammatory profile such as bactericidal capacity and the ability to promote Th1 polarization over Th2 responses. In this regard, NFAT5 upregulated the Th1-stimulatory cytokine IL-12 in classically activated macrophages, whereas in alternatively polarized ones it enhanced the expression of the pro-Th1 mediators Fizz-1 and arginase 1, indicating that it could promote proinflammatory readiness by regulating independent genes in differently polarized macrophages. Finally, adoptive transfer assays in vivo revealed a reduced antitumor capacity in NFAT5-deficient macrophages against syngeneic Lewis lung carcinoma and ID8 ovarian carcinoma cells, a defect that in the ID8 model was associated with a reduced accumulation of effector CD8 T cells at the tumor site. Altogether, detailed analysis of the effect of NFAT5 in pro- and anti-inflammatory macrophages uncovered its ability to regulate distinct genes under both polarization modes and revealed its predominant role in promoting proinflammatory macrophage functions. Copyright © 2017 by The American Association of Immunologists, Inc.

  6. DMPD: The oxidation of lipoproteins by monocytes-macrophages. Biochemical andbiological mechanisms. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10473535 The oxidation of lipoproteins by monocytes-macrophages. Biochemical andbio.... (.png) (.svg) (.html) (.csml) Show The oxidation of lipoproteins by monocytes-macrophages. Biochemical and...onocytes-macrophages. Biochemical andbiological mechanisms. Authors Chisolm GM 3rd, Hazen SL, Fox PL, Cathca

  7. DMPD: Pathogen-induced apoptosis of macrophages: a common end for different pathogenicstrategies. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11207583 Pathogen-induced apoptosis of macrophages: a common end for different path...ml) Show Pathogen-induced apoptosis of macrophages: a common end for different pathogenicstrategies. PubmedI...D 11207583 Title Pathogen-induced apoptosis of macrophages: a common end for diff

  8. DMPD: Mechanism of age-associated up-regulation in macrophage PGE2 synthesis. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15331118 Mechanism of age-associated up-regulation in macrophage PGE2 synthesis. Wu...e-associated up-regulation in macrophage PGE2 synthesis. PubmedID 15331118 Title Mechanism of age-associated... up-regulation in macrophage PGE2 synthesis. Authors Wu D, Meydani SN. Publicatio

  9. MiR-146a modulates macrophage polarization by inhibiting Notch1 pathway in RAW264.7 macrophages.

    Science.gov (United States)

    Huang, Cheng; Liu, Xue-Jiao; QunZhou; Xie, Juan; Ma, Tao-Tao; Meng, Xiao-Ming; Li, Jun

    2016-03-01

    Macrophages are heterogeneous and plastic cells which are able to undergo dynamic transition between M1 and M2 polarized phenotypes in response to the microenvironment signals. However, the underlying molecular mechanisms of macrophage polarization are still obscure. In the current study, it was revealed that miR-146a might play a pivotal role in macrophage polarization. As our results indicated, miR-146a was highly expressed in M2 macrophages rather than M1 macrophages. Over-expression of miR-146a resulted in significantly decreased production of pro-inflammatory cytokines including iNOS and TNF-α in M1 macrophages, while increased production of M2 marker genes such as Arg1 and CD206 in M2 macrophages. In contrast, knockdown of miR-146a promoted M1 macrophage polarization but diminished M2 macrophage polarization. Mechanistically, it was revealed that miR-146a modulated macrophage polarization by targeting Notch1. Of note, PPARγ was responsible as another target for miR-146a-mediated macrophage polarization. Taken together, it was suggested that miR-146a might serve as a molecular regulator in macrophage polarization and is a potential therapeutic target for inflammatory diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. DMPD: Molecular mechanisms of macrophage activation and deactivation bylipopolysaccharide: roles of the receptor complex. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14609719 Molecular mechanisms of macrophage activation and deactivation bylipopolys...acol Ther. 2003 Nov;100(2):171-94. (.png) (.svg) (.html) (.csml) Show Molecular mechanisms of macrophage act...medID 14609719 Title Molecular mechanisms of macrophage activation and deactivation bylipopolysaccharide: ro

  11. 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

  12. Bacteroides fragilis interferes with iNOS activity and leads to pore formation in macrophage surface

    International Nuclear Information System (INIS)

    Vieira, Jessica Manya B.D.; Vallim, Deyse C.; Ferreira, Eliane O.; Seabra, Sergio H.; Vommaro, Rossiane C.; Avelar, Katia E.S.; De Souza, Wanderley; Ferreira, Maria Ca-hat ndida S.; Domingues, Regina M.C.P.

    2005-01-01

    Bacteroides fragilis is the anaerobe most commonly recoverable from clinical specimens. The wide genetic diversity of this bacterium related with virulence potential is still an open question. In this study, we analyzed the morphological aspects and microbicide action of MO during interactions with B. fragilis. A filamentous cytoplasm content release and a different actin organization colocalized with iNOS were detected. It was also possible to observe the reduction of NO production in the same conditions. The scanning electron microscopy showed the formation of pore-like structures in the surface of macrophages in the bacterial presence and by transmission electron microscopy we could observe the extrusion of cytoplasm contents as well as the condensation of chromatin in the nucleus periphery. These data suggest the existence of an inhibitory mechanism developed by B. fragilis strains for one of the macrophage microbicide actions

  13. Yersinia pestis and host macrophages: immunodeficiency of mouse macrophages induced by YscW.

    Science.gov (United States)

    Bi, Yujing; Du, Zongmin; Han, Yanping; Guo, Zhaobiao; Tan, Yafang; Zhu, Ziwen; Yang, Ruifu

    2009-09-01

    The virulence of the pathogenic Yersinia species depends on a plasmid-encoded type III secretion system (T3SS) that transfers six Yersinia outer protein (Yop) effector proteins into the cytoplasm of eukaryotic cells, leading to disruption of host defence mechanisms. It is shown in this study that Yersinia pestis YscW, a protein of the T3SS injectisome, contributes to the induction of a deficiency in phagocytosis in host macrophages and a reduction in their antigen-presenting capacity. A Y. pestis strain lacking yscW had no effect on uptake by host macrophages. In mice infected with wild-type Y. pestis, the yscW mutant or a complement strain, immunodeficiency was observed in host macrophages compared with those from uninfected mice. However, the phagocytosis and antigen presenting capacities of macrophages infected by yscW mutant strain both in vivo and in vitro were significantly higher than those by wild type strain. Consistent with this finding, when YscW was expressed in the RAW264.7 macrophage cell line, phagocytosis and antigen-presenting capacities were significantly lower than those of the control groups. These results indicate that Y. pestis YscW may directly induce immunodeficiency in murine macrophages by crippling their phagocytosis and antigen-presenting capacities. These data provide evidences to Y. pestis pathogenesis that some proteins in T3SS injectisome, such as YscW protein, might play independent roles in disrupting host defense apart from their known functions.

  14. Macrophage-Mediated Lymphangiogenesis: The Emerging Role of Macrophages as Lymphatic Endothelial Progenitors

    International Nuclear Information System (INIS)

    Ran, Sophia; Montgomery, Kyle E.

    2012-01-01

    It is widely accepted that macrophages and other inflammatory cells support tumor progression and metastasis. During early stages of neoplastic development, tumor-infiltrating macrophages (TAMs) mount an immune response against transformed cells. Frequently, however, cancer cells escape the immune surveillance, an event that is accompanied by macrophage transition from an anti-tumor to a pro-tumorigenic type. The latter is characterized by high expression of factors that activate endothelial cells, suppress immune response, degrade extracellular matrix, and promote tumor growth. Cumulatively, these products of TAMs promote tumor expansion and growth of both blood and lymphatic vessels that facilitate metastatic spread. Breast cancers and other epithelial malignancies induce the formation of new lymphatic vessels (i.e., lymphangiogenesis) that leads to lymphatic and subsequently, to distant metastasis. Both experimental and clinical studies have shown that TAMs significantly promote tumor lymphangiogenesis through paracrine and cell autonomous modes. The paracrine effect consists of the expression of a variety of pro-lymphangiogenic factors that activate the preexisting lymphatic vessels. The evidence for cell-autonomous contribution is based on the observed tumor mobilization of macrophage-derived lymphatic endothelial cell progenitors (M-LECP) that integrate into lymphatic vessels prior to sprouting. This review will summarize the current knowledge of macrophage-dependent growth of new lymphatic vessels with specific emphasis on an emerging role of macrophages as lymphatic endothelial cell progenitors (M-LECP)

  15. Phagocytosis of Giardia muris by macrophages in Peyer's patch epithelium in mice.

    OpenAIRE

    Owen, R L; Allen, C L; Stevens, D P

    1981-01-01

    No mechanism for the initiation of immunological clearance of Giardia from the mammalian intestinal tract has been identified. In normal and nude mice experimentally infected with G. muris, we examined antigen-sampling epithelium over Peyer's patch follicles by electron microscopy for evidence of interaction between G. muris and lymphoid cells. Invading G. muris were found in the epithelium near dying or desquamating columnar cells. Macrophages beneath the basal lamina extended pseudopods int...

  16. The Use of Quality Benchmarking in Assessing Web Resources for the Dermatology Virtual Branch Library of the National electronic Library for Health (NeLH)

    OpenAIRE

    Boulos, MN Kamel; Roudsari, AV; Gordon, C; Gray, JA Muir

    2001-01-01

    Background In 1998, the U.K. National Health Service Information for Health Strategy proposed the implementation of a National electronic Library for Health to provide clinicians, healthcare managers and planners, patients and the public with easy, round the clock access to high quality, up-to-date electronic information on health and healthcare. The Virtual Branch Libraries are among the most important components of the National electronic Library for Health . They aim at creating online kno...

  17. Molecular Mechanisms Modulating the Phenotype of Macrophages and Microglia

    Directory of Open Access Journals (Sweden)

    Stephanie A. Amici

    2017-11-01

    Full Text Available Macrophages and microglia play crucial roles during central nervous system development, homeostasis and acute events such as infection or injury. The diverse functions of tissue macrophages and microglia are mirrored by equally diverse phenotypes. A model of inflammatory/M1 versus a resolution phase/M2 macrophages has been widely used. However, the complexity of macrophage function can only be achieved by the existence of varied, plastic and tridimensional macrophage phenotypes. Understanding how tissue macrophages integrate environmental signals via molecular programs to define pathogen/injury inflammatory responses provides an opportunity to better understand the multilayered nature of macrophages, as well as target and modulate cellular programs to control excessive inflammation. This is particularly important in MS and other neuroinflammatory diseases, where chronic inflammatory macrophage and microglial responses may contribute to pathology. Here, we perform a comprehensive review of our current understanding of how molecular pathways modulate tissue macrophage phenotype, covering both classic pathways and the emerging role of microRNAs, receptor-tyrosine kinases and metabolism in macrophage phenotype. In addition, we discuss pathway parallels in microglia, novel markers helpful in the identification of peripheral macrophages versus microglia and markers linked to their phenotype.

  18. Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?

    Science.gov (United States)

    Baci, Denisa; Tremolati, Marco; Fanuli, Matteo; Farronato, Giampietro; Mortara, Lorenzo

    2018-01-01

    Macrophages are key cellular components of the innate immunity, acting as the main player in the first-line defence against the pathogens and modulating homeostatic and inflammatory responses. Plasticity is a major feature of macrophages resulting in extreme heterogeneity both in normal and in pathological conditions. Macrophages are not homogenous, and they are generally categorized into two broad but distinct subsets as either classically activated (M1) or alternatively activated (M2). However, macrophages represent a continuum of highly plastic effector cells, resembling a spectrum of diverse phenotype states. Induction of specific macrophage functions is closely related to the surrounding environment that acts as a relevant orchestrator of macrophage functions. This phenomenon, termed polarization, results from cell/cell, cell/molecule interaction, governing macrophage functionality within the hosting tissues. Here, we summarized relevant cellular and molecular mechanisms driving macrophage polarization in “distant” pathological conditions, such as cancer, type 2 diabetes, atherosclerosis, and periodontitis that share macrophage-driven inflammation as a key feature, playing their dual role as killers (M1-like) and/or builders (M2-like). We also dissect the physio/pathological consequences related to macrophage polarization within selected chronic inflammatory diseases, placing polarized macrophages as a relevant hallmark, putative biomarkers, and possible target for prevention/therapy. PMID:29507865

  19. Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?

    Directory of Open Access Journals (Sweden)

    Luca Parisi

    2018-01-01

    Full Text Available Macrophages are key cellular components of the innate immunity, acting as the main player in the first-line defence against the pathogens and modulating homeostatic and inflammatory responses. Plasticity is a major feature of macrophages resulting in extreme heterogeneity both in normal and in pathological conditions. Macrophages are not homogenous, and they are generally categorized into two broad but distinct subsets as either classically activated (M1 or alternatively activated (M2. However, macrophages represent a continuum of highly plastic effector cells, resembling a spectrum of diverse phenotype states. Induction of specific macrophage functions is closely related to the surrounding environment that acts as a relevant orchestrator of macrophage functions. This phenomenon, termed polarization, results from cell/cell, cell/molecule interaction, governing macrophage functionality within the hosting tissues. Here, we summarized relevant cellular and molecular mechanisms driving macrophage polarization in “distant” pathological conditions, such as cancer, type 2 diabetes, atherosclerosis, and periodontitis that share macrophage-driven inflammation as a key feature, playing their dual role as killers (M1-like and/or builders (M2-like. We also dissect the physio/pathological consequences related to macrophage polarization within selected chronic inflammatory diseases, placing polarized macrophages as a relevant hallmark, putative biomarkers, and possible target for prevention/therapy.

  20. HIV Infection of Macrophages: Implications for Pathogenesis and Cure

    Directory of Open Access Journals (Sweden)

    Kiera Leigh Clayton

    2017-05-01

    Full Text Available Although CD4+ T cells represent the major reservoir of persistent HIV and SIV infection, accumulating evidence suggests that macrophages also contribute. However, investigations of the role of macrophages are often underrepresented at HIV pathogenesis and cure meetings. This was the impetus for a scientific workshop dedicated to this area of study, held in Cambridge, MA in January 2017. The workshop brought together experts in the fields of HIV/SIV immunology/virology, macrophage biology and immunology, and animal models of HIV/SIV infection to facilitate discussions regarding the role of macrophages as a physiologically relevant viral reservoir, and the implications of macrophage infection for HIV pathogenesis and cure strategies. An emerging consensus that infected macrophages likely persist in the setting of combination antiretroviral therapy, driving persistent inflammation and contributing to the viral reservoir, indicate the importance of addressing macrophages as well as CD4+ T cells with future therapeutic strategies.

  1. Lysosomal Disorders Drive Susceptibility to Tuberculosis by Compromising Macrophage Migration

    Science.gov (United States)

    Berg, Russell D.; Levitte, Steven; O’Sullivan, Mary P.; O’Leary, Seónadh M.; Cambier, C.J.; Cameron, James; Takaki, Kevin K.; Moens, Cecilia B.; Tobin, David M.; Keane, Joseph; Ramakrishnan, Lalita

    2016-01-01

    Summary A zebrafish genetic screen for determinants of susceptibility to Mycobacterium marinum identified a hypersusceptible mutant deficient in lysosomal cysteine cathepsins that manifests hallmarks of human lysosomal storage diseases. Under homeostatic conditions, mutant macrophages accumulate undigested lysosomal material, which disrupts endocytic recycling and impairs their migration to, and thus engulfment of, dying cells. This causes a buildup of unengulfed cell debris. During mycobacterial infection, macrophages with lysosomal storage cannot migrate toward infected macrophages undergoing apoptosis in the tuberculous granuloma. The unengulfed apoptotic macrophages undergo secondary necrosis, causing granuloma breakdown and increased mycobacterial growth. Macrophage lysosomal storage similarly impairs migration to newly infecting mycobacteria. This phenotype is recapitulated in human smokers, who are at increased risk for tuberculosis. A majority of their alveolar macrophages exhibit lysosomal accumulations of tobacco smoke particulates and do not migrate to Mycobacterium tuberculosis. The incapacitation of highly microbicidal first-responding macrophages may contribute to smokers’ susceptibility to tuberculosis. PMID:27015311

  2. The role of substrate morphology for the cytokine release profile of immature human primary macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Bartneck, Matthias [Department of Medicine III, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen (Germany); Heffels, Karl-Heinz [Department and Chair of Functional Materials in Medicine and Dentistry, University of Würzburg, Pleicherwall 2, 97070 Würzburg (Germany); Bovi, Manfred [Electron Microscopic Facility, Medical Faculty, RWTH Aachen (Germany); Groll, Jürgen [Department and Chair of Functional Materials in Medicine and Dentistry, University of Würzburg, Pleicherwall 2, 97070 Würzburg (Germany); Zwadlo-Klarwasser, Gabriele [Interdisciplinary Center for Clinical Research and Dept. of Dermatology, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52056 Aachen (Germany)

    2013-12-01

    There is increasing evidence that the physicochemical nature of any given material is a dominant factor for the release of cytokines by innate immune cells, specifically of macrophages, and thus majorly influences their interaction with other cell types. Recently, we could show that the 3D structure of star shaped polytheylene oxide–polypropylene oxide co-polymers (sP(EO-stat-PO))-hydrogel coated substrates has a stronger influence on the release pattern of cytokines after 7 days of culture than surface chemistry. Here, we focused on the analysis of cytokine release over time and a more detailed analysis of cell morphology by scanning electron microscopy (SEM). Therefore, we compared different strategies for SEM sample preparation and found that using osmium tetroxide combined with aqua bidest led to best preparation results. For cytokine release we show significant changes from day 3 to day 7 of cell culture. After 3 days, the sP(EO-stat-PO)-coated substrates led to an induction of pro-angiogenic CCL3 and CCL4, and of low amounts of the anti-inflammatory IL10, which declined at day 7. In contrast, pleiotropic IL6 and the pro-inflammatory TNFα and IL1β were expressed stronger at day 7 than at day 3. - Highlights: • Strategies for the preparation of macrophages on hydrogel materials (Fig. 1) • Cytokine release of immature macrophages on the substrates (Fig. 2 and Table 1) • Changes in cytokine release during macrophage maturation (Table 2)

  3. Dynamics of HIV-containing compartments in macrophages reveal sequestration of virions and transient surface connections.

    Directory of Open Access Journals (Sweden)

    Raphaël Gaudin

    Full Text Available During HIV pathogenesis, infected macrophages behave as "viral reservoirs" that accumulate and retain virions within dedicated internal Virus-Containing Compartments (VCCs. The nature of VCCs remains ill characterized and controversial. Using wild-type HIV-1 and a replication-competent HIV-1 carrying GFP internal to the Gag precursor, we analyzed the biogenesis and evolution of VCCs in primary human macrophages. VCCs appear roughly 14 hours after viral protein synthesis is detected, initially contain few motile viral particles, and then mature to fill up with virions that become packed and immobile. The amount of intracellular Gag, the proportion of dense VCCs, and the density of viral particles in their lumen increased with time post-infection. In contrast, the secretion of virions, their infectivity and their transmission to T cells decreased overtime, suggesting that HIV-infected macrophages tend to pack and retain newly formed virions into dense compartments. A minor proportion of VCCs remains connected to the plasma membrane overtime. Surprisingly, live cell imaging combined with correlative light and electron microscopy revealed that such connections can be transient, highlighting their dynamic nature. Together, our results shed light on the late phases of the HIV-1 cycle and reveal some of its macrophage specific features.

  4. The role of substrate morphology for the cytokine release profile of immature human primary macrophages

    International Nuclear Information System (INIS)

    Bartneck, Matthias; Heffels, Karl-Heinz; Bovi, Manfred; Groll, Jürgen; Zwadlo-Klarwasser, Gabriele

    2013-01-01

    There is increasing evidence that the physicochemical nature of any given material is a dominant factor for the release of cytokines by innate immune cells, specifically of macrophages, and thus majorly influences their interaction with other cell types. Recently, we could show that the 3D structure of star shaped polytheylene oxide–polypropylene oxide co-polymers (sP(EO-stat-PO))-hydrogel coated substrates has a stronger influence on the release pattern of cytokines after 7 days of culture than surface chemistry. Here, we focused on the analysis of cytokine release over time and a more detailed analysis of cell morphology by scanning electron microscopy (SEM). Therefore, we compared different strategies for SEM sample preparation and found that using osmium tetroxide combined with aqua bidest led to best preparation results. For cytokine release we show significant changes from day 3 to day 7 of cell culture. After 3 days, the sP(EO-stat-PO)-coated substrates led to an induction of pro-angiogenic CCL3 and CCL4, and of low amounts of the anti-inflammatory IL10, which declined at day 7. In contrast, pleiotropic IL6 and the pro-inflammatory TNFα and IL1β were expressed stronger at day 7 than at day 3. - Highlights: • Strategies for the preparation of macrophages on hydrogel materials (Fig. 1) • Cytokine release of immature macrophages on the substrates (Fig. 2 and Table 1) • Changes in cytokine release during macrophage maturation (Table 2)

  5. Tubular lysosome morphology and distribution within macrophages depend on the integrity of cytoplasmic microtubules

    International Nuclear Information System (INIS)

    Swanson, J.; Bushnell, A.; Silverstein, S.C.

    1987-01-01

    Pinocytosis of the fluorescent dye lucifer yellow labels elongated, membrane-bound tubular organelles in several cell types, including cultured human monocytes, thioglycolate-elicited mouse peritoneal macrophages, and the macrophage-like cell line J774.2. These tubular structures can be identified as lysosomes by acid phosphatase histochemistry and immunofluorescence localization of cathepsin L. The abundance of tubular lysosomes is markedly increased by treatment with phorbol 12-myristate 13-acetate. When labeled by pinocytosis of microperoxidase and examined by electron microscopic histochemistry, the tubular lysosomes have an outside diameter of ≅ 75 nm and a length of several micrometers; they radiate from the cell's centrosphere in alignment with cytoplasmic microtubules and intermediate filaments. Incubation of phorbol myristate acetate-treated macrophages at 4 0 C or in medium containing 5 μM colchicine or nocodazole at 37 0 C leads to disassembly of microtubules and fragmentation of the tubular lysosomes. Return of the cultures to 37 0 C or removal of nocodazole from the medium leads to reassembly of microtubules and the reappearance of tubular lysosomes within 10-20 min. The authors conclude that microtubules are essential for the maintenance of tubular lysosome morphology and that, in macrophages, a significant proportion of the lysosomal compartment is contained within these tubular structures

  6. Analysis on Current Situation and Countermeasure of Domestic Electronic Commerce Logistics in the Internet Age——Based on Resource Dependence Theory

    Directory of Open Access Journals (Sweden)

    Zhang Jiapeng

    2017-01-01

    Full Text Available This paper analyzes the status of electric business logistics in the current Internet era in China, and combines the SWOT analysis with AHP to do the empirical analysis, then puts forward the countermeasure that the electric business logistics resource should be shared based on the resource dependence theory. Through the empirical analysis, it is found that the disadvantages and opportunities of the logistics status are important in the Internet era.The resource sharing strategy based on the resource dependence theory is more scientific. The rational use of Internet technology in electric business logistics industry can achieve “sharing”. It is of great significance for its balanced development, intelligent development and optimization and development.

  7. Macrophage mitochondrial oxidative stress promotes atherosclerosis and nuclear factor-κB-mediated inflammation in macrophages.

    Science.gov (United States)

    Wang, Ying; Wang, Gary Z; Rabinovitch, Peter S; Tabas, Ira

    2014-01-31

    Mitochondrial oxidative stress (mitoOS) has been shown to correlate with the progression of human atherosclerosis. However, definitive cell type-specific causation studies in vivo are lacking, and the molecular mechanisms of potential proatherogenic effects remain to be determined. Our aims were to assess the importance of macrophage mitoOS in atherogenesis and to explore the underlying molecular mechanisms. We first validated Western diet-fed Ldlr(-/-) mice as a model of human mitoOS-atherosclerosis association by showing that non-nuclear oxidative DNA damage, a marker of mitoOS in lesional macrophages, correlates with aortic root lesion development. To investigate the importance of macrophage mitoOS, we used a genetic engineering strategy in which the OS suppressor catalase was ectopically expressed in mitochondria (mCAT) in macrophages. MitoOS in lesional macrophages was successfully suppressed in these mice, and this led to a significant reduction in aortic root lesional area. The mCAT lesions had less monocyte-derived cells, less Ly6c(hi) monocyte infiltration into lesions, and lower levels of monocyte chemotactic protein-1. The decrease in lesional monocyte chemotactic protein-1 was associated with the suppression of other markers of inflammation and with decreased phosphorylation of RelA (NF-κB p65), indicating decreased activation of the proinflammatory NF-κB pathway. Using models of mitoOS in cultured macrophages, we showed that mCAT suppressed monocyte chemotactic protein-1 expression by decreasing the activation of the IκB-kinase β-RelA NF-κB pathway. MitoOS in lesional macrophages amplifies atherosclerotic lesion development by promoting NF-κB-mediated entry of monocytes and other inflammatory processes. In view of the mitoOS-atherosclerosis link in human atheromata, these findings reveal a potentially new therapeutic target to prevent the progression of atherosclerosis.

  8. CD163-Macrophages Are Involved in Rhabdomyolysis-Induced Kidney Injury and May Be Detected by MRI with Targeted Gold-Coated Iron Oxide Nanoparticles.

    Science.gov (United States)

    Rubio-Navarro, Alfonso; Carril, Mónica; Padro, Daniel; Guerrero-Hue, Melanie; Tarín, Carlos; Samaniego, Rafael; Cannata, Pablo; Cano, Ainhoa; Villalobos, Juan Manuel Amaro; Sevillano, Ángel Manuel; Yuste, Claudia; Gutiérrez, Eduardo; Praga, Manuel; Egido, Jesús; Moreno, Juan Antonio

    2016-01-01

    Macrophages play an important role in rhabdomyolysis-acute kidney injury (AKI), although the molecular mechanisms involved in macrophage differentiation are poorly understood. We analyzed the expression and regulation of CD163, a membrane receptor mainly expressed by anti-inflammatory M2 macrophages, in rhabdomyolysis-AKI and developed targeted probes for its specific detection in vivo by MRI. Intramuscular injection of glycerol in mice promoted an early inflammatory response, with elevated proportion of M1 macrophages, and partial differentiation towards a M2 phenotype in later stages, where increased CD163 expression was observed. Immunohistological studies confirmed the presence of CD163-macrophages in human rhabdomyolysis-AKI. In cultured macrophages, myoglobin upregulated CD163 expression via HO-1/IL-10 axis. Moreover, we developed gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody that specifically targeted CD163 in kidneys from glycerol-injected mice, as determined by MRI studies, and confirmed by electron microscopy and immunological analysis. Our findings are the first to demonstrate that CD163 is present in both human and experimental rhabdomyolysis-induced AKI, suggesting an important role of this molecule in this pathological condition. Therefore, the use of probes targeting CD163-macrophages by MRI may provide important information about the cellular composition of renal lesion in rhabdomyolysis.

  9. Rare pneumoconiosis induced by long-term amorphous silica exposure: the histological characteristics and expression of cyclooxygenase-2 as an antifibrogenic mediator in macrophages.

    Science.gov (United States)

    Kumasaka, Toshio; Akaike, Yasushi; Nakamura, Osamu; Yamazaki, Kazuma; Moriyama, Hiroshi; Takemura, Tamiko

    2011-11-01

    Pneumoconiosis induced by non-crystalline silica is considered rare, although silicosis resulting from contact with crystalline silica is a well-known hazard associated with progressive pulmonary fibrosis. Here we describe a patient with pneumoconiosis induced by diatomaceous earth composed of amorphous silica detected by two-dimensional imaging of chemical elements. The histology revealed that the disease was characterized by a granulomatous reaction in the lung. A large number of macrophages laden with yellow and black pigments accumulated in alveolar spaces and were incorporated into the interstitial sites. Bronchiolar walls were destroyed by palisade macrophages, suggesting airflow obstruction. Packed macrophages adhering to and covering the denuded interstitium indicated that macrophages might be incorporated into pulmonary interstitium in this fashion. Immunohistochemistry showed that cyclooxygenase-2, an antifibrogenic mediator, was intensely expressed in the macrophages compared with macrophages in control lungs. No birefringent material was found in the tissues. When two-dimensional analysis of chemical elements was performed using an electron probe microanalyzer with a wavelength-dispersive spectrometer, the resultant fine mapping of silicon and oxygen on the tissue indicated that the pigments phagocytosed by macrophages corresponded to amorphous silica. In conclusion, two-dimensional analysis of elements is very useful for pathologists in correlating the presence of chemical elements with histological changes. © 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.

  10. Leishmania hijacking of the macrophage intracellular compartments.

    Science.gov (United States)

    Liévin-Le Moal, Vanessa; Loiseau, Philippe M

    2016-02-01

    Leishmania spp., transmitted to humans by the bite of the sandfly vector, are responsible for the three major forms of leishmaniasis, cutaneous, diffuse mucocutaneous and visceral. Leishmania spp. interact with membrane receptors of neutrophils and macrophages. In macrophages, the parasite is internalized within a parasitophorous vacuole and engages in a particular intracellular lifestyle in which the flagellated, motile Leishmania promastigote metacyclic form differentiates into non-motile, metacyclic amastigote form. This phenomenon is induced by Leishmania-triggered events leading to the fusion of the parasitophorous vacuole with vesicular members of the host cell endocytic pathway including recycling endosomes, late endosomes and the endoplasmic reticulum. Maturation of the parasitophorous vacuole leads to the intracellular proliferation of the Leishmania amastigote forms by acquisition of host cell nutrients while escaping host defense responses. © 2015 FEBS.

  11. Molecular Characterization of Macrophage-Biomaterial Interactions.

    Science.gov (United States)

    Moore, Laura Beth; Kyriakides, Themis R

    2015-01-01

    Implantation of biomaterials in vascularized tissues elicits the sequential engagement of molecular and cellular elements that constitute the foreign body response. Initial events include the non-specific adsorption of proteins to the biomaterial surface that render it adhesive for cells such as neutrophils and macrophages. The latter undergo unique activation and in some cases undergo cell-cell fusion to form foreign body giant cells that contribute to implant damage and fibrotic encapsulation. In this review, we discuss the molecular events that contribute to macrophage activation and fusion with a focus on the role of the inflammasome, signaling pathways such as JAK/STAT and NF-κB, and the putative involvement of micro RNAs in the regulation of these processes.

  12. Purinergic signaling to terminate TLR responses in macrophages

    Directory of Open Access Journals (Sweden)

    Kajal eHamidzadeh

    2016-03-01

    Full Text Available Macrophages undergo profound physiological alterations when they encounter pathogen associated molecular patterns (PAMPs. These alterations can result in the elaboration of cytokines and mediators that promote immune responses and contribute to the clearance of pathogens. These innate immune responses by myeloid cells are transient. The termination of these secretory responses is not due to the dilution of stimuli, but rather to the active down-regulation of innate responses induced by the very PAMPs that initiated them. Here we describe a purinergic autoregulatory program whereby TLR-stimulated macrophages control their activation state. In this program, TLR stimulated macrophages undergo metabolic alterations that result in the production of ATP and its release through membrane pannexin channels. This purine nucleotide is rapidly hydrolyzed to adenosine by ectoenzymes on the macrophage surface, CD39 and CD73. Adenosine then signals through the P1 class of seven transmembrane receptors to induce a regulatory state that is characterized by the down-regulation of inflammatory cytokines and the production of anti-inflammatory cytokines and growth factors. This purinergic autoregulatory system mitigates the collateral damage that would be caused by the prolonged activation of macrophages, and rather allows the macrophage to maintain homeostasis. The transient activation of macrophages can be prolonged by treating macrophages with IFN-γ. IFN-γ treated macrophages become less sensitive to the regulatory effects of adenosine, allowing them to sustain macrophage activation for the duration of an adaptive immune response.

  13. Macrophage Phenotype and Function in Different Stages of Atherosclerosis

    Science.gov (United States)

    Tabas, Ira; Bornfeldt, Karin E.

    2016-01-01

    The remarkable plasticity and plethora of biological functions performed by macrophages have enticed scientists to study these cells in relation to atherosclerosis for more than 50 years, and major discoveries continue to be made today. It is now understood that macrophages play important roles in all stages of atherosclerosis, from initiation of lesions and lesion expansion, to necrosis leading to rupture and the clinical manifestations of atherosclerosis, to resolution and regression of atherosclerotic lesions. Lesional macrophages are derived primarily from blood monocytes, although recent research has shown that lesional macrophage-like cells can also be derived from smooth muscle cells. Lesional macrophages take on different phenotypes depending on their environment and which intracellular signaling pathways are activated. Rather than a few distinct populations of macrophages, the phenotype of the lesional macrophage is more complex and likely changes during the different phases of atherosclerosis and with the extent of lipid and cholesterol loading, activation by a plethora of receptors, and metabolic state of the cells. These different phenotypes allow the macrophage to engulf lipids, dead cells, and other substances perceived as danger signals; efflux cholesterol to HDL; proliferate and migrate; undergo apoptosis and death; and secrete a large number of inflammatory and pro-resolving molecules. This review article, part of the Compendium on Atherosclerosis, discusses recent advances in our understanding of lesional macrophage phenotype and function in different stages of atherosclerosis. With the increasing understanding of the roles of lesional macrophages, new research areas and treatment strategies are beginning to emerge. PMID:26892964

  14. Human Induced Pluripotent Stem Cell-Derived Macrophages for Unraveling Human Macrophage Biology.

    Science.gov (United States)

    Zhang, Hanrui; Reilly, Muredach P

    2017-11-01

    Despite a substantial appreciation for the critical role of macrophages in cardiometabolic diseases, understanding of human macrophage biology has been hampered by the lack of reliable and scalable models for cellular and genetic studies. Human induced pluripotent stem cell (iPSC)-derived macrophages (IPSDM), as an unlimited source of subject genotype-specific cells, will undoubtedly play an important role in advancing our understanding of the role of macrophages in human diseases. In this review, we summarize current literature in the differentiation and characterization of IPSDM at phenotypic, functional, and transcriptomic levels. We emphasize the progress in differentiating iPSC to tissue resident macrophages, and in understanding the ontogeny of in vitro differentiated IPSDM that resembles primitive hematopoiesis, rather than adult definitive hematopoiesis. We review the application of IPSDM in modeling both Mendelian genetic disorders and host-pathogen interactions. Finally, we highlighted the potential areas of research using IPSDM in functional validation of coronary artery disease loci in genome-wide association studies, functional genomic analyses, drug testing, and cell therapeutics in cardiovascular diseases. © 2017 American Heart Association, Inc.

  15. Misbehaving macrophages in the pathogenesis of psoriasis

    OpenAIRE

    Clark, Rachael A.; Kupper, Thomas S.

    2006-01-01

    Psoriasis is a chronic inflammatory skin disease unique to humans. In this issue of the JCI, 2 studies of very different mouse models of psoriasis both report that macrophages play a key role in inducing psoriasis-like skin disease. Psoriasis is clearly a polygenic, inherited disease of uncontrolled cutaneous inflammation. The debate that currently rages in the field is whether psoriasis is a disease of autoreactive T cells or whether it reflects an intrinsic defect within the skin — or both....

  16. Molecular Characterization of Macrophage-Biomaterial Interactions

    OpenAIRE

    Moore, Laura Beth; Kyriakides, Themis R.

    2015-01-01

    Implantation of biomaterials in vascularized tissues elicits the sequential engagement of molecular and cellular elements that constitute the foreign body response. Initial events include the non-specific adsorption of proteins to the biomaterial surface that render it adhesive for cells such as neutrophils and macrophages. The latter undergo unique activation and in some cases undergo cell-cell fusion to form foreign body giant cells that contribute to implant damage and fibrotic encapsulati...

  17. Macrophage specific drug delivery in experimental leishmaniasis.

    Science.gov (United States)

    Basu, Mukul Kumar; Lala, Sanchaita

    2004-09-01

    Macrophage-specific delivery systems are the subject of much interest nowadays, because of the fact that macrophages act as host cells for many parasites and bacteria, which give rise to outbreak of so many deadly diseases(eg. leishmaniasis, tuberculosis etc.) in humans. To combat these deadly diseases initially macrophage specific liposomal delivery system were thought of and tested in vivo against experimental leishmaniasis in hamsters using a series of indigenous or synthetic antileishmanial compounds and the results were critically discussed. In vitro testing was also done against macrophages infected with Leishmania donovani, the causative agent for visceral leishmaniasis. The common problem of liposome therapy being their larger size, stability and storage, non-ionic surfactant vesicles, niosomes were prepared, for their different drug distribution and release characteristics compared to liposomes. When tested in vivo, the retention capacity of niosomes was found to be higher than that of liposomes due to the absence of lipid molecules and their smaller size. Thus the therapeutic efficacy of certain antileishmanial compounds was found to be better than that in the liposomal form. The niosomes, being cheaper, less toxic, biodegradable and non-immunogenic, were considered for sometime as suitable alternatives to liposomes as drug carriers. Besides the advent of other classical drugs carriers(e.g. neoglycoproteins), the biggest challenge came from polymeric delivery vehicles, specially the polymeric nanoparticles which were made of cost effective biodegradable polymers and different natural polymers. Because of very small size and highly stable nature, use of nanoparticles as effective drug carriers has been explored in experimental leishmaniasis using a series of antileishmanial compounds, both of indigenous and synthetic origin. The feasibility of application in vivo, when tested for biological as well as for other physicochemical parameters, the polymeric

  18. M2 polarization enhances silica nanoparticle uptake by macrophages

    Directory of Open Access Journals (Sweden)

    Jessica eHoppstädter

    2015-03-01

    Full Text Available While silica nanoparticles have enabled numerous industrial and medical applications, their toxicological safety requires further evaluation. Macrophages are the major cell population responsible for nanoparticle clearance in vivo. The prevailing macrophage phenotype largely depends on the local immune status of the host. Whereas M1-polarized macrophages are considered as pro-inflammatory macrophages involved in host defense, M2 macrophages exhibit anti-inflammatory and wound-healing properties, but also promote tumor growth.We employed different models of M1 and M2 polarization: GM-CSF/LPS/IFN-gamma was used to generate primary human M1 cells and M-CSF/IL-10 to differentiate M2 monocyte-derived macrophages. PMA-differentiated THP-1 cells were polarized towards an M1 type by LPS/IFN-gamma and towards M2 by IL-10. Uptake of fluorescent silica nanoparticles (Ø 26 and 41 nm and microparticles (Ø 1.75 µm was quantified. At the concentration used (50 µg/ml, silica nanoparticles did not influence cell viability as assessed by MTT assay. Nanoparticle uptake was enhanced in M2-polarized primary human monocyte-derived macrophages compared with M1 cells, as shown by flow cytometric and microscopic approaches. In contrast, the uptake of microparticles did not differ between M1 and M2 phenotypes. M2 polarization was also associated with increased nanoparticle uptake in the macrophage-like THP-1 cell line. In accordance, in vivo polarized M2-like primary human tumor-associated macrophages (TAM obtained from lung tumors took up more nanoparticles than M1-like alveolar macrophages isolated from the surrounding lung tissue.In summary, our data indicate that the M2 polarization of macrophages promotes nanoparticle internalization. Therefore, the phenotypical differences between macrophage subsets should be taken into consideration in future investigations on nanosafety, but might also open up therapeutic perspectives allowing to specifically target M2

  19. Legumain is activated in macrophages during pancreatitis

    Science.gov (United States)

    Wartmann, Thomas; Fleming, Alicia K.; Gocheva, Vasilena; van der Linden, Wouter A.; Withana, Nimali P.; Verdoes, Martijn; Aurelio, Luigi; Edgington-Mitchell, Daniel; Lieu, TinaMarie; Parker, Belinda S.; Graham, Bim; Reinheckel, Thomas; Furness, John B.; Joyce, Johanna A.; Storz, Peter; Halangk, Walter; Bogyo, Matthew; Bunnett, Nigel W.

    2016-01-01

    Pancreatitis is an inflammatory disease of the pancreas characterized by dysregulated activity of digestive enzymes, necrosis, immune infiltration, and pain. Repeated incidence of pancreatitis is an important risk factor for pancreatic cancer. Legumain, a lysosomal cysteine protease, has been linked to inflammatory diseases such as atherosclerosis, stroke, and cancer. Until now, legumain activation has not been studied during pancreatitis. We used a fluorescently quenched activity-based probe to assess legumain activation during caerulein-induced pancreatitis in mice. We detected activated legumain by ex vivo imaging, confocal microscopy, and gel electrophoresis. Compared with healthy controls, legumain activity in the pancreas of caerulein-treated mice was increased in a time-dependent manner. Legumain was localized to CD68+ macrophages and was not active in pancreatic acinar cells. Using a small-molecule inhibitor of legumain, we found that this protease is not essential for the initiation of pancreatitis. However, it may serve as a biomarker of disease, since patients with chronic pancreatitis show strongly increased legumain expression in macrophages. Moreover, the occurrence of legumain-expressing macrophages in regions of acinar-to-ductal metaplasia suggests that this protease may influence reprogramming events that lead to inflammation-induced pancreatic cancer. PMID:27514475

  20. Pegylated silica nanoparticles: cytotoxicity and macrophage uptake

    Science.gov (United States)

    Glorani, Giulia; Marin, Riccardo; Canton, Patrizia; Pinto, Marcella; Conti, Giamaica; Fracasso, Giulio; Riello, Pietro

    2017-08-01

    Here, we present a thorough study of pegylated silica nanoparticle (SNP) interaction with different biological environments. The SNPs have a mean diameter of about 40 nm and are coated with polyethylene glycol (PEG) of different molecular weights. The physicochemical characterization of SNPs allowed the confirmation of the binding of PEG chains to the silica surface, the reproducibility of the synthesis and the narrow size-dispersion. In view of clarifying the SNP interaction with biological environments, we first assessed the SNP reactivity after the incubation with two cell lines (macrophages RAW 264.7 and primary human fibroblasts), observing a reduced toxicity of pegylated SNPs compared to the bare ones. Then, we investigated the effect of the protein adsorption on the SNP surface using the model serum protein, bovine serum albumin (BSA). We found that the protein adsorption takes place more heavily on poorly pegylated SNPs, promoting the uptake of the latter by macrophages and leading to an increased mortality of these cells. To better understand this mechanism by means of flow cytometry, the dye Ru(bpy)3Cl2 was incorporated in the SNPs. The overall results highlight the SNP potentialities as a drug delivery system, thanks to the low interactions with the macrophages.

  1. Burkholderia pseudomallei transcriptional adaptation in macrophages

    Directory of Open Access Journals (Sweden)

    Chieng Sylvia

    2012-07-01

    Full Text Available Abstract Background Burkholderia pseudomallei is a facultative intracellular pathogen of phagocytic and non-phagocytic cells. How the bacterium interacts with host macrophage cells is still not well understood and is critical to appreciate the strategies used by this bacterium to survive and how intracellular survival leads to disease manifestation. Results Here we report the expression profile of intracellular B. pseudomallei following infection of human macrophage-like U937 cells. During intracellular growth over the 6 h infection period, approximately 22 % of the B. pseudomallei genome showed significant transcriptional adaptation. B. pseudomallei adapted rapidly to the intracellular environment by down-regulating numerous genes involved in metabolism, cell envelope, motility, replication, amino acid and ion transport system and regulatory function pathways. Reduced expression in catabolic and housekeeping genes suggested lower energy requirement and growth arrest during macrophage infection, while expression of genes encoding anaerobic metabolism functions were up regulated. However, whilst the type VI secretion system was up regulated, expression of many known virulence factors was not significantly modulated over the 6hours of infection. Conclusions The transcriptome profile described here provides the first comprehensive view of how B. pseudomallei survives within host cells and will help identify potential virulence factors and proteins that are important for the survival and growth of B. pseudomallei within human cells.

  2. Decreased expression of liver X receptor-α in macrophages infected with Chlamydia pneumoniae in human atherosclerotic arteries in situ.

    Science.gov (United States)

    Bobryshev, Yuri V; Orekhov, Alexander N; Killingsworth, Murray C; Lu, Jinhua

    2011-01-01

    In in vitro experiments, Chlamydia pneumoniae has been shown to infect macrophages and to accelerate foam cell formation. It has been hypothesized that the C. pneumoniae infection affects foam cell formation by suppressing the expression of liver X receptors (LXR), but whether such an event occurs in human atherosclerosis is not known. In this study we examined carotid artery segments, obtained by endarterectomy, in which the presence of C. pneumoniae was confirmed by both polymerase chain reaction and immunohistochemistry. The expression of LXR-α in macrophages infected with C. pneumoniae and macrophages that were not infected was compared using a quantitative immunohistochemical analysis. The analysis revealed a 2.2-fold reduction in the expression of LXR-α in C. pneumoniae-infected cells around the lipid cores in atherosclerotic plaques. In the cytoplasm of laser-capture microdissected cells that were immunopositive for C. pneumoniae, electron microscopy demonstrated the presence of structures with the appearance of elementary, reticulate and aberrant bodies of C. pneumoniae. We conclude that LXR-α expression is reduced in C. pneumoniae-infected macrophages in human atherosclerotic lesions which supports the hypothesis that C. pneumoniae infection might suppress LXR expression in macrophages transforming into foam cells. Copyright © 2011 S. Karger AG, Basel.

  3. Origins and Hallmarks of Macrophages: Development, Homeostasis, and Disease

    Science.gov (United States)

    Wynn, Thomas A.; Chawla, Ajay; Pollard, Jeffrey W.

    2013-01-01

    Preface Macrophages the most plastic cells of the hematopoietic system are found in all tissues and exhibit great functional diversity. They have roles in development, homeostasis, tissue repair, and immunity. While anatomically distinct, resident tissue macrophages exhibit different transcriptional profiles, and functional capabilities, they are all required for the maintenance of homeostasis. However, these reparative and homeostatic functions can be subverted by chronic insults, resulting in a causal association of macrophages with disease states. In this review, we discuss how macrophages regulate normal physiology and development and provide several examples of their pathophysiologic roles in disease. We define the “hallmarks” of macrophages performing particular functions, taking into account novel insights into the diversity of their lineages, identity, and regulation. This diversity is essential to understand because macrophages have emerged as important therapeutic targets in many important human diseases. PMID:23619691

  4. Regulation of macrophage development and function in peripheral tissues

    Science.gov (United States)

    Lavin, Yonit; Mortha, Arthur; Rahman, Adeeb; Merad, Miriam

    2015-01-01

    Macrophages are immune cells of haematopoietic origin that provide crucial innate immune defence and have tissue-specific functions in the regulation and maintenance of organ homeostasis. Recent studies of macrophage ontogeny, as well as transcriptional and epigenetic identity, have started to reveal the decisive role of the tissue stroma in the regulation of macrophage function. These findings suggest that most macrophages seed the tissues during embryonic development and functionally specialize in response to cytokines and metabolites that are released by the stroma and drive the expression of unique transcription factors. In this Review, we discuss how recent insights into macrophage ontogeny and macrophage–stroma interactions contribute to our understanding of the crosstalk that shapes macrophage function and the maintenance of organ integrity. PMID:26603899

  5. Tumor-Associated Macrophages in Oncolytic Virotherapy: Friend or Foe?

    Directory of Open Access Journals (Sweden)

    Nicholas L. Denton

    2016-07-01

    Full Text Available Cancer therapy remains a challenge due to toxicity limitations of chemotherapy and radiation therapy. Oncolytic viruses that selectively replicate and destroy cancer cells are of increasing interest. In addition to direct cell lysis, these vectors stimulate an anti-tumor immune response. A key regulator of tumor immunity is the tumor-associated macrophage population. Macrophages can either support oncolytic virus therapy through pro-inflammatory stimulation of the anti-tumor response at the cost of hindering direct oncolysis or through immunosuppressive protection of virus replication at the cost of hindering the anti-tumor immune response. Despite similarities in macrophage interaction between adult and pediatric tumors and the abundance of research supporting macrophage modulation in adult tumors, there are few studies investigating macrophage modulation in pediatric cancers or modulation of immunotherapy. We review the current state of knowledge regarding macrophages in cancers and their influence on oncolytic virotherapy.

  6. How Students Learn: Ways of Thinking about "Good Learning" in HE. EDNER (Formative Evaluation of the Distributed National Electronic Resource) Project. Issues Paper.

    Science.gov (United States)

    Manchester Metropolitan Univ. (England).

    This issues paper, one of a series of eight, is intended to distill formative evaluation questions on topics that are central to the development of the higher and further education information environment in the United Kingdom. The topic of this first issues paper is a conceptual framework that can help members of a project (information resource)…

  7. Role of Macrophage-Induced Inflammation in Mesothelioma

    Science.gov (United States)

    2011-07-01

    macrophages). Normal pleura becomes available intermittently , serving to slow the completion of this task. All is set in place for us to complete the...GFP) regulated by a Csf1r-promoter (Sasmono et al. 2003) show that macrophages travel up and down these fibers at a fast rate and also “jump” between...2010). Macrophages have also recently been shown to be important in adipogenesis at least during obesity , through their secretion of adipocyte growth

  8. 大學圖書館電子資源之需求分析與行銷策略之研究 A Study of Demands Analysis and Marketing Strategy of Electronic Resources in University Library

    Directory of Open Access Journals (Sweden)

    Huang-Yu Liu

    2008-03-01

    Full Text Available 電子資源的出現,使得知識載體有了新的突破,提高了使用者的便利性與即時性。對於圖書館而言,如何使電子資源的使用效益達到最高,必須思考一套有效的行銷策略。電子資源行銷概念應以讀者為導向,尊重讀者的資訊需求,並利用各種宣傳技巧,行銷電子資源,使圖書館能提供更完善的服務。本研究之目的旨在探討讀者的使用需求及電子資源的推廣策略,以獲致最有效益的行銷方式。研究對象以開南大學日間部四學院(商學院、運輸觀光學院、資訊學院、人文社會學院)學生為樣本,佐以缺口分析模型為分析架構,藉以找出個案中讀者/學生對於電子資源使用的真實需求,並進而歸納出提供服務的大學圖書館在其推廣或行銷服務上可有的因應策略。The emergence of electronic resources has made new breakthrough in knowledge carriers because of their ease of use, instant availability, and the characteristic of no time and space constraints. For public libraries to achieve maximum efficiency in its electronic resources, it is necessary to seek the most effective marketing strategies. Therefore, the marketing concept of the electronic resources should be reader oriented, such as respecting and understanding library user’s information needs. Libraries also need to utilize various media and techniques to market the electronic resources, so that more comprehensive services and experiences can be provided to readers. The purpose of this study is to investigate library user’s needs and promotion strategies of electronic resources in order to identify the most effective ways of marketing. This study focuses on the students of the four colleges (College of Business, College of Tourism, College of Information, and College of Humanities and Social Science in Kainan University as subjects in the survey questionnaire. It uses the Gap Analysis

  9. Macrophages: contributors to allograft dysfunction, repair, or innocent bystanders?

    Science.gov (United States)

    Mannon, Roslyn B

    2012-02-01

    Macrophages are members of the innate immune response. However, their role in the adaptive immune response is not known. The purpose of this review is to highlight our current understanding of macrophage structure and function and how they may participate in allograft injury. Studies in acute kidney injury models identify macrophages as key mediators of inflammatory injury, while more recent studies indicate that they may play a reparative role, depending on phenotype - M1 or M2 type macrophages. Mregs, generated in vitro, appear to have immune suppressive abilities and a unique phenotype. In solid-organ transplant, the emphasis of studies has been on acute or chronic injury. These data are derived from animal models using depletion of macrophages or antagonizing their activation and inflammatory responses. The relative contribution of macrophage phenotype in transplantation has not been explored. These studies suggest that macrophages play an injurious role in acute cellular allograft rejection, as well as in chronic injury. Infiltration of an allograft with macrophages is also associated with worse graft function and poor prognosis. Further studies are needed to understand the mechanisms of macrophage-mediated injury, explore their potential reparative role, and determine if they or their functional products are biomarkers of poor graft outcomes.

  10. L-Plastin promotes podosome longevity and supports macrophage motility

    Science.gov (United States)

    Zhou, Julie Y.; Szasz, Taylor P.; Stewart-Hutchinson, Phillip J.; Sivapalan, Janardan; Todd, Elizabeth M.; Deady, Lauren E.; Cooper, John A.; Onken, Michael D.; Morley, S. Celeste

    2016-01-01

    Elucidating the molecular regulation of macrophage migration is essential for understanding the patho-physiology of multiple human diseases, including host responses to infection and autoimmune disorders. Macrophage migration is supported by dynamic rearrangements of the actin cytoskeleton, with formation of actin-based structures such as podosomes and lamellipodia. Here we provide novel insights into the function of the actin-bundling protein l-plastin (LPL) in primary macrophages. We found that podosome stability is disrupted in primary resident peritoneal macrophages from LPL−/− mice. Live-cell imaging of F-actin using resident peritoneal macrophages from LifeACT-RFP+ mice demonstrated that loss of LPL led to decreased longevity of podosomes, without reducing the number of podosomes initiated. Additionally, macrophages from LPL−/− mice failed to elongate in response to chemotactic stimulation. These deficiencies in podosome stabilization and in macrophage elongation correlated with impaired macrophage transmigration in culture and decreased monocyte migration into murine peritoneum. Thus, we have identified a role for LPL in stabilizing long-lived podosomes and in enabling macrophage motility. PMID:27614263

  11. Functional modifications of macrophage activity after sublethal irradiation

    International Nuclear Information System (INIS)

    Swartz, R.P.

    1982-01-01

    The modifications of macrophage activity following sublethal irradiation, both in vivo and in vitro, were studied using spreading and C3b-receptor-mediated ingestion assays. Nonelicited peritoneal washout cells were examined for changes in activity and selected population characteristics. The cells from irradiated mice were from a resident peritoneal population and not immigrating cells. The macrophage population showed enhanced activity early with a refractory period (24-48) when the macrophages were unresponsive to stimulation by irradiated lymphocytes. The enhanced activity was inversely dose dependent on macrophage. The lymphocytes showed a regulatory function(s) on the time post irradiation at which they were examined. Early lymphocytes exhibited the ability to enhance the activity of normal macrophages while lymphocytes removed 24 hours post irradiation could suppress the activity of already activated macrophages. The effect(s) of the various lymphocyte populations were reproduced with cell-free supernatants which was indicative of the production of lymphokines. Separation on nylon wool columns indicated that the activity resided primarily in the T-cell population of lymphocytes. In vitro irradiation indicated that stimulation of the lymphocytes is macrophage dependent. Additional work indicated that sublethally irradiated macrophages did not inhibit replication of the coccidian protozoon Toxoplasma gondii although they did show increased phagocytosis. Examination of the serum from whole body irradiated mice showed the presence of a postirradiation substance which enhanced the phagocytosis of normal macrophages. It was not present in the serum of normal mice and was not endotoxin

  12. Macrophage migration inhibitory factor is associated with aneurysmal expansion

    DEFF Research Database (Denmark)

    Pan, Jie-Hong; Lindholt, Jes Sanddal; Sukhova, Galina K

    2003-01-01

    Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine released mainly from macrophages and activated lymphocytes. Both atherosclerosis and abdominal aortic aneurysm (AAA) are inflammatory diseases tightly linked to the function of these cells. The correlation and contribution o...... of MIF to these human diseases remain unknown, although a recent rabbit study showed expression of this cytokine in atherosclerotic lesions.......Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine released mainly from macrophages and activated lymphocytes. Both atherosclerosis and abdominal aortic aneurysm (AAA) are inflammatory diseases tightly linked to the function of these cells. The correlation and contribution...

  13. Application of electronic learning tools for training of specialists in the field of information technologies for enterprises of mineral resources sector

    Directory of Open Access Journals (Sweden)

    Е. В. Катунцов

    2017-08-01

    Full Text Available The article shows the advantages of using modern electronic learning tools in the training of specialists for the mineral and raw materials complex and considers the basic principles of organizing training using these tools. The experience of using electronic learning tools using foreign teaching materials and involving foreign professors is described. A special attention is given to the electronic learning environment of the Cisco Networking Academy – Cisco NetAcad. The experience of teaching at the Networking Academy of the Saint-Petersburg Mining University is described. Details are given to modern virtual environments for laboratory work, such as Cisco Packet Tracer, GNS3 and Emulated Virtual Environment. The experience of using electronic learning technologies at the University of Economics of Bratislava is considered. It actively cooperates with a number of universities of other countries, such as the University of International Business (Almaty, the Eurasian National University named after LN Gumilyov (Astana and the Institute of Social and Humanitarian Knowledge (Kazan.

  14. An operational utility assessment [electronic resource]: measuring the effectiveness of the Joint Concept Technology Demonstration (JCTD), Joint Forces Protection Advance Security System (JFPASS)

    OpenAIRE

    McGovern, Mark; Mayor, Jeffrey D.; Symmes, Joseph

    2008-01-01

    MBA Professional Report Planning modern military operations requires an accurate intelligence assessment of potential threats, combined with a detailed assessment of the physical theater of operations. This information can then be combined with equipment and manpower resources to set up a logistically supportable operation that mitigates as much of the enemy threat as possible. Given such a daunting challenge, military planners often turn to intelligent software agents to support their...

  15. Positive Perceptions of Access to Online Library Resources Correlates with Quality and Quantity of Scholarly Publications among Finnish Academics. A Review of: Vakkari, Pertti. “Perceived Influence of the Use of Electronic Information Resources on Scholarly Work and Publication Productivity.” Journal of the American Society for Information Science and Technology 59.4 (Feb. 15, 2008: 602-12.

    Directory of Open Access Journals (Sweden)

    Scott Marsalis

    2008-12-01

    Full Text Available Objective – To investigate the relationship between academics’ use of library electronic resources and their opinions regarding how these resources have impacted their work, and to investigate the association between this perceived influence and publication productivity during the previous two years.Design – Two specific questions added to an annual online user-survey questionnaire; additional data mined from surveySetting – Twenty-two Finnish Universities served by FinELib, the Finnish Electronic Library.Subjects – Seven hundred and sixty seven academic staff and full-time doctoral students.Methods – A questionnaire was posted in April 2007 on FinELib’s homepage and advertised on each university library’s mainpage, and focused on respondents’ experience in the previous two years. Participants selected answers either from a list of category choices, or, when measuring perceptions, by rating agreement with statements along a four-point scale. Controlled variables measured were the respondents’ academic position, their discipline, membership in a research group, whether their literature use was discipline-specific or interdisciplinary, and their perception of the availability online of the relevant core literature. The independent variable measured was the scholars’ perception of the impact of the use of electronic library resources on their work. The dependent variable measured was the scholars’ self-reported publications in the two years preceding the survey.Main Results – Participants reported a positive impact on the efficiency of their work, most strongly in areas of ease of access, with lesser impacts in the range of materials available to them and the ease with which they can keep up-to-date in their field. To a lesser extent, the scholars perceived a positive impact on the quality of their work. Upon analysis, the study found that access to online library resources improved scholars’ work by the interconnected

  16. In vitro studies of interaction of rickettsia and macrophages: effect of ultraviolet light on Coxiella burnetti inactivation and macrophage enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Little, J.S.; Kishimoto, R.A.; Canonico, P.G.

    1980-03-01

    The inactivation of Coxiella burnetii in suspension or in cultures of guinea pig peritoneal macrophages by ultraviolet (uv) light was studied. The effect of uv treatment on the activity of macrophage organelle marker enzymes and their subsequent equilibration in linear sucrose gradients was also determined. It was shown that uv treatment for 15 s at a distance of 10 cm inactivated C. burnetti, either in suspension or within guinea pig peritoneal macrophages. Similar uv treatment had little effect on the activity or equilibration of macrophage organelle marker enzymes in linear sucrose gradients.

  17. Moderate restriction of macrophage-tropic human immunodeficiency virus type 1 by SAMHD1 in monocyte-derived macrophages.

    Science.gov (United States)

    Taya, Kahoru; Nakayama, Emi E; Shioda, Tatsuo

    2014-01-01

    Macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains are able to grow to high titers in human monocyte-derived macrophages. However, it was recently reported that cellular protein SAMHD1 restricts HIV-1 replication in human cells of the myeloid lineage, including monocyte-derived macrophages. Here we show that degradation of SAMHD1 in monocyte-derived macrophages was associated with moderately enhanced growth of the macrophage-tropic HIV-1 strain. SAMHD1 degradation was induced by treating target macrophages with vesicular stomatitis virus glycoprotein-pseudotyped human immunodeficiency virus type 2 (HIV-2) particles containing viral protein X. For undifferentiated monocytes, HIV-2 particle treatment allowed undifferentiated monocytes to be fully permissive for productive infection by the macrophage-tropic HIV-1 strain. In contrast, untreated monocytes were totally resistant to HIV-1 replication. These results indicated that SAMHD1 moderately restricts even a macrophage-tropic HIV-1 strain in monocyte-derived macrophages, whereas the protein potently restricts HIV-1 replication in undifferentiated monocytes.

  18. Macrophage heterogeneity and cholesterol homeostasis: classically-activated macrophages are associated with reduced cholesterol accumulation following treatment with oxidized LDL.

    Science.gov (United States)

    Chu, Eugene M; Tai, Daven C; Beer, Jennifer L; Hill, John S

    2013-02-01

    Macrophages are centrally involved during atherosclerosis development and are the predominant cell type that accumulates cholesterol in the plaque. Macrophages however, are heterogeneous in nature reflecting a variety of microenvironments and different phenotypes may be more prone to contribute towards atherosclerosis progression. Using primary human monocyte-derived macrophages, we sought to evaluate one aspect of atherogenic potential of different macrophage phenotypes by determining their propensity to associate with and accumulate oxidized low density lipoprotein (oxLDL). Classically-activated macrophages treated simultaneously with interferon γ (IFNγ) and tumor necrosis factor α (TNFα) associated with less oxLDL and accumulated less cholesterol compared to untreated controls. The combined treatment of IFNγ and TNFα reduced the mRNA expression of CD36 and the expression of both cell surface CD36 and macrophage scavenger receptor 1 (MSR1) protein. Under oxLDL loaded conditions, IFNγ and TNFα did not reduce macrophage protein expression of the transcription factor peroxisome proliferator-actived receptor γ (PPARγ) which is known to positively regulate CD36 expression. However, macrophages treated with IFNγ attenuated the ability of the PPARγ-specific agonist rosiglitazone from upregulating cell surface CD36 protein expression. Our results demonstrate that the observed reduction of cholesterol accumulation in macrophages treated with IFNγ and TNFα following oxLDL treatment was due at least in part to reduced cell surface CD36 and MSR1 protein expression. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. In vitro studies of interaction of rickettsia and macrophages: effect of ultraviolet light on Coxiella burnetti inactivation and macrophage enzymes

    International Nuclear Information System (INIS)

    Little, J.S.; Kishimoto, R.A.; Canonico, P.G.

    1980-01-01

    The inactivation of Coxiella burnetii in suspension or in cultures of guinea pig peritoneal macrophages by ultraviolet (uv) light was studied. The effect of uv treatment on the activity of macrophage organelle marker enzymes and their subsequent equilibration in linear sucrose gradients was also determined. It was shown that uv treatment for 15 s at a distance of 10 cm inactivated C. burnetti, either in suspension or within guinea pig peritoneal macrophages. Similar uv treatment had little effect on the activity or equilibration of macrophage organelle marker enzymes in linear sucrose gradients

  20. DMPD: Signal integration between IFNgamma and TLR signalling pathways in macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16920490 Signal integration between IFNgamma and TLR signalling pathways in macroph...tml) (.csml) Show Signal integration between IFNgamma and TLR signalling pathways in macrophages. PubmedID 16920490 Title Signal inte...gration between IFNgamma and TLR signalling pathways in

  1. Modulation of human macrophage activity by Ascaris antigens is dependent on macrophage polarization state

    DEFF Research Database (Denmark)

    Almeida, Sara; Nejsum, Peter; Williams, Andrew R.

    2018-01-01

    Parasitic worms (helminths) are known to actively modulate host immune responses and inflammation. The aim of this study was to investigate if adult body fluid (ABF) from the helminth Ascaris suum has immunomodulatory effects on different subtypes of human monocyte-derived macrophages (Mɸ) in vitro...

  2. Nicotinamide: a vitamin able to shift macrophage differentiation toward macrophages with restricted inflammatory features.

    Science.gov (United States)

    Weiss, Ronald; Schilling, Erik; Grahnert, Anja; Kölling, Valeen; Dorow, Juliane; Ceglarek, Uta; Sack, Ulrich; Hauschildt, Sunna

    2015-11-01

    The differentiation of human monocytes into macrophages is influenced by environmental signals. Here we asked in how far nicotinamide (NAM), a vitamin B3 derivative known to play a major role in nicotinamide adenine dinucleotide (NAD)-mediated signaling events, is able to modulate monocyte differentiation into macrophages developed in the presence of granulocyte macrophage colony-stimulating factor (GM-MØ) or macrophage colony-stimulating factor (M-MØ). We found that GM-MØ undergo biochemical, morphological and functional modifications in response to NAM, whereas M-MØ were hardly affected. GM-MØ exposed to NAM acquired an M-MØ-like structure while the LPS-induced production of pro-inflammatory cytokines and COX-derived eicosanoids were down-regulated. In contrast, NAM had no effect on the production of IL-10 or the cytochrome P450-derived eicosanoids. Administration of NAM enhanced intracellular NAD concentrations; however, it did not prevent the LPS-mediated drain on NAD pools. In search of intracellular molecular targets of NAM known to be involved in LPS-induced cytokine and eicosanoid synthesis, we found NF-κB activity to be diminished. In conclusion, our data show that vitamin B3, when present during the differentiation of monocytes into GM-MØ, interferes with biochemical pathways resulting in strongly reduced pro-inflammatory features. © The Author(s) 2015.

  3. Immunomodulatory Molecule IRAK-M Balances Macrophage Polarization and Determines Macrophage Responses during Renal Fibrosis.

    Science.gov (United States)

    Steiger, Stefanie; Kumar, Santhosh V; Honarpisheh, Mohsen; Lorenz, Georg; Günthner, Roman; Romoli, Simone; Gröbmayr, Regina; Susanti, Heni-Eka; Potempa, Jan; Koziel, Joanna; Lech, Maciej

    2017-08-15

    Activation of various innate immune receptors results in IL-1 receptor-associated kinase (IRAK)-1/IRAK-4-mediated signaling and secretion of proinflammatory cytokines such as IL-12, IL-6, or TNF-α, all of which are implicated in tissue injury and elevated during tissue remodeling processes. IRAK-M, also known as IRAK-3, is an inhibitor of proinflammatory cytokine and chemokine expression in intrarenal macrophages. Innate immune activation contributes to both acute kidney injury and tissue remodeling that is associated with chronic kidney disease (CKD). Our study assessed the contribution of macrophages in CKD and the role of IRAK-M in modulating disease progression. To evaluate the effect of IRAK-M in chronic renal injury in vivo, a mouse model of unilateral ureteral obstruction (UUO) was employed. The expression of IRAK-M increased within 2 d after UUO in obstructed compared with unobstructed kidneys. Mice deficient in IRAK-M were protected from fibrosis and displayed a diminished number of alternatively activated macrophages. Compared to wild-type mice, IRAK-M-deficient mice showed reduced tubular injury, leukocyte infiltration, and inflammation following renal injury as determined by light microscopy, immunohistochemistry, and intrarenal mRNA expression of proinflammatory and profibrotic mediators. Taken together, these results strongly support a role for IRAK-M in renal injury and identify IRAK-M as a possible modulator in driving an alternatively activated profibrotic macrophage phenotype in UUO-induced CKD. Copyright © 2017 by The American Association of Immunologists, Inc.

  4. Polyglucose nanoparticles with renal elimination and macrophage avidity facilitate PET imaging in ischaemic heart disease

    NARCIS (Netherlands)

    Keliher, Edmund J.; Ye, Yu-Xiang; Wojtkiewicz, Gregory R.; Aguirre, Aaron D.; Tricot, Benoit; Senders, Max L.; Groenen, Hannah; Fay, Francois; Perez-Medina, Carlos; Calcagno, Claudia; Carlucci, Giuseppe; Reiner, Thomas; Sun, Yuan; Courties, Gabriel; Iwamoto, Yoshiko; Kim, Hye-Yeong; Wang, Cuihua; Chen, John W.; Swirski, Filip K.; Wey, Hsiao-Ying; Hooker, Jacob; Fayad, Zahi A.; Mulder, Willem J. M.; Weissleder, Ralph; Nahrendorf, Matthias

    2017-01-01

    Tissue macrophage numbers vary during health versus disease. Abundant inflammatory macrophages destruct tissues, leading to atherosclerosis, myocardial infarction and heart failure. Emerging therapeutic options create interest in monitoring macrophages in patients. Here we describe positron emission

  5. Macrophage Efferocytosis and Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2018-03-01

    E) ELISA for total CXCL1 and CXCL5 levels in supernatants of MΦs alone or cocultured with RM1(HA) or PC3(HA). (F) Transcriptional activ- ity cell...marrow macrophages (Fig- ure 1D). ELISA evaluation for CXCL1 and CXCL5 proteins in the coculture media for apoptotic cancer cells (Figure 1E) confirmed... ELISA analysis of total pro- tein lysates from VEH- (n = 10) and AP-treated (n = 11) tumor vossicles. (G) Graphs depicting the correlation between

  6. Power Electronics

    DEFF Research Database (Denmark)

    Iov, Florin; Ciobotaru, Mihai; Blaabjerg, Frede

    2008-01-01

    is to change the electrical power production sources from the conventional, fossil (and short term) based energy sources to renewable energy resources. The other is to use high efficient power electronics in power generation, power transmission/distribution and end-user application. This paper discuss the most...... emerging renewable energy sources, wind energy, which by means of power electronics are changing from being a minor energy source to be acting as an important power source in the energy system. Power electronics is the enabling technology and the presentation will cover the development in wind turbine...... technology from kW to MW, discuss which power electronic solutions are most feasible and used today....

  7. 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.

  8. Differential S1P Receptor Profiles on M1- and M2-Polarized Macrophages Affect Macrophage Cytokine Production and Migration.

    Science.gov (United States)

    Müller, Jan; von Bernstorff, Wolfram; Heidecke, Claus-Dieter; Schulze, Tobias

    2017-01-01

    Introduction . Macrophages are key players in complex biological processes. In response to environmental signals, macrophages undergo polarization towards a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that acts via 5 G-protein coupled receptors (S1P 1-5 ) in order to influence a broad spectrum of biological processes. This study assesses S1P receptor expression on macrophages before and after M1 and M2 polarization and performs a comparative analysis of S1P signalling in the two activational states of macrophages. Methods . Bone marrow derived macrophages (BMDM) from C57 BL/6 mice were cultured under either M1- or M2-polarizing conditions. S1P-receptor expression was determined by quantitative RT-PCR. Influence of S1P on macrophage activation, migration, phagocytosis, and cytokine secretion was assessed in vitro. Results . All 5 S1P receptor subclasses were expressed in macrophages. Culture under both M1- and M2-polarizing conditions led to significant downregulation of S1P 1 . In contrast, M1-polarized macrophages significantly downregulated S1P 4 . The expression of the remaining three S1P receptors did not change. S1P increased expression of iNOS under M2-polarizing conditions. Furthermore, S1P induced chemotaxis in M1 macrophages and changed cytokine production in M2 macrophages. Phagocytosis was not affected by S1P-signalling. Discussion . The expression of different specific S1P receptor profiles may provide a possibility to selectively influence M1- or M2-polarized macrophages.

  9. Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages

    KAUST Repository

    Roy, Sugata; Schmeier, Sebastian; Kaczkowski, Bogumil; Arner, Erik; Alam, Tanvir; Ozturk, Mumin; Tamgue, Ousman; Parihar, Suraj P.; Kawaji, Hideya; Itoh, Masayoshi; Lassmann, Timo; Carninci, Piero; Hayashizaki, Yoshihide; Forrest, Alistair R. R.; Guler, Reto; Bajic, Vladimir B.; Brombacher, Frank; Suzuki, Harukazu

    2018-01-01

    landscape of IFNγ (M1) or IL-4/IL-13 (M2) stimulated macrophages during Mtb infection in a time-kinetic manner. Mtb infection widely and drastically altered macrophage-specific gene expression, which is far larger than that of M1 or M2 activations. Gene

  10. DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas

    DEFF Research Database (Denmark)

    Herrtwich, Laura; Nanda, Indrajit; Evangelou, Konstantinos

    2016-01-01

    to a chronic stimulus, though critical for disease outcome, have not been defined. Here, we delineate a macrophage differentiation pathway by which a persistent Toll-like receptor (TLR) 2 signal instructs polyploid macrophage fate by inducing replication stress and activating the DNA damage response. Polyploid...

  11. Niacin and its metabolites as master regulators of macrophage activation.

    Science.gov (United States)

    Montserrat-de la Paz, Sergio; Naranjo, M Carmen; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J Garcia; Bermudez, Beatriz

    2017-01-01

    Niacin is a broad-spectrum lipid-regulating drug used for clinical therapy of chronic high-grade inflammatory diseases. However, the mechanisms by which either niacin or the byproducts of its catabolism ameliorate these inflammatory diseases are not clear yet. Human circulating monocytes and mature macrophages were used to analyze the effects of niacin and its metabolites (NAM, NUA and 2-Pyr) on oxidative stress, plasticity and inflammatory response by using biochemical, flow cytometry, quantitative real-time PCR and Western blot technologies. Niacin, NAM and 2-Pyr significantly decreased ROS, NO and NOS2 expression in LPS-treated human mature macrophages. Niacin and NAM skewed macrophage polarization toward antiinflammatory M2 macrophage whereas a trend toward proinflammatory M1 macrophage was noted following treatment with NUA. Niacin and NAM also reduced the inflammatory competence of LPS-treated human mature macrophages and promoted bias toward antiinflammatory CD14 + CD16 ++ nonclassical human primary monocytes. This study reveals for the first time that niacin and its metabolites possess antioxidant, reprogramming and antiinflammatory properties on human primary monocytes and monocyte-derived macrophages. Our findings imply a new understanding of the mechanisms by which niacin and its metabolites favor a continuous and gradual plasticity process in the human monocyte/macrophage system. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Epigenetic pathways in macrophages emerge as novel targets in atherosclerosis

    NARCIS (Netherlands)

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

    2015-01-01

    Atherosclerosis is a lipid-driven chronic inflammatory disorder. Monocytes and macrophages are key immune cells in the development of disease and clinical outcome. It is becoming increasingly clear that epigenetic pathways govern many aspects of monocyte and macrophage differentiation and

  13. Consistent inhibition of cyclooxygenase drives macrophages towards the inflammatory phenotype.

    Directory of Open Access Journals (Sweden)

    Yi Rang Na

    Full Text Available Macrophages play important roles in defense against infection, as well as in homeostasis maintenance. Thus alterations of macrophage function can have unexpected pathological results. Cyclooxygenase (COX inhibitors are widely used to relieve pain, but the effects of long-term usage on macrophage function remain to be elucidated. Using bone marrow-derived macrophage culture and long-term COX inhibitor treatments in BALB/c mice and zebrafish, we showed that chronic COX inhibition drives macrophages into an inflammatory state. Macrophages differentiated in the presence of SC-560 (COX-1 inhibitor, NS-398 (COX-2 inhibitor or indomethacin (COX-1/2 inhibitor for 7 days produced more TNFα or IL-12p70 with enhanced p65/IκB phosphoylation. YmI and IRF4 expression was reduced significantly, indicative of a more inflammatory phenotype. We further observed that indomethacin or NS-398 delivery accelerated zebrafish death rates during LPS induced sepsis. When COX inhibitors were released over 30 days from an osmotic pump implant in mice, macrophages from peritoneal cavities and adipose tissue produced more TNFα in both the basal state and under LPS stimulation. Consequently, indomethacin-exposed mice showed accelerated systemic inflammation after LPS injection. Our findings suggest that macrophages exhibit a more inflammatory phenotype when COX activities are chronically inhibited.

  14. Nanomedicine Strategies to Target Tumor-Associated Macrophages

    NARCIS (Netherlands)

    Binnemars-Postma, Karin A.; Storm, G; Prakash, Jai

    2017-01-01

    In recent years, the influence of the tumor microenvironment (TME) on cancer progression has been better understood. Macrophages, one of the most important cell types in the TME, exist in different subtypes, each of which has a different function. While classically activated M1 macrophages are

  15. Nanomedicine strategies to target tumor-associated macrophages

    NARCIS (Netherlands)

    Binnemars-Postma, Karin; Storm, Gert; Prakash, Jai

    2017-01-01

    In recent years, the influence of the tumor microenvironment (TME) on cancer progression has been better understood. Macrophages, one of the most important cell types in the TME, exist in different subtypes, each of which has a different function. While classically activated M1 macrophages are

  16. Biomaterials Influence Macrophage-Mesenchymal Stem Cell Interaction In Vitro

    NARCIS (Netherlands)

    N. Grotenhuis (Nienke); S.F. De Witte (Samantha Fh); G.J.V.M. van Osch (Gerjo); Y. Bayon (Yves); J.F. Lange (Johan); Y.M. Bastiaansen-Jenniskens (Yvonne)

    2016-01-01

    textabstractBackground: Macrophages and mesenchymal stem cells (MSCs) are important cells in wound healing. We hypothesized that the cross-talk between macrophages and adipose tissue-derived MSCs (ASCs) is biomaterial dependent, thereby influencing processes involved in wound healing. Materials and

  17. Macrophages are critical effectors of antibody therapies for cancer.

    Science.gov (United States)

    Weiskopf, Kipp; Weissman, Irving L

    2015-01-01

    Macrophages are innate immune cells that derive from circulating monocytes, reside in all tissues, and participate in many states of pathology. Macrophages play a dichotomous role in cancer, where they promote tumor growth but also serve as critical immune effectors of therapeutic antibodies. Macrophages express all classes of Fcγ receptors, and they have immense potential to destroy tumors via the process of antibody-dependent phagocytosis. A number of studies have demonstrated that macrophage phagocytosis is a major mechanism of action of many antibodies approved to treat cancer. Consequently, a number of approaches to augment macrophage responses to therapeutic antibodies are under investigation, including the exploration of new targets and development of antibodies with enhanced functions. For example, the interaction of CD47 with signal-regulatory protein α (SIRPα) serves as a myeloid-specific immune checkpoint that limits the response of macrophages to antibody therapies, and CD47-blocking agents overcome this barrier to augment phagocytosis. The response of macrophages to antibody therapies can also be enhanced with engineered Fc variants, bispecific antibodies, or antibody-drug conjugates. Macrophages have demonstrated success as effectors of cancer immunotherapy, and further investigation will unlock their full potential for the benefit of patients.

  18. Of macrophages and red blood cells; a complex love story

    NARCIS (Netherlands)

    de Back, Djuna Z.; Kostova, Elena B.; van Kraaij, Marian; van den Berg, Timo K.; van Bruggen, Robin

    2014-01-01

    Macrophages tightly control the production and clearance of red blood cells (RBC). During steady state hematopoiesis, approximately 10(10) RBC are produced per hour within erythroblastic islands in humans. In these erythroblastic islands, resident bone marrow macrophages provide erythroblasts with

  19. Of macrophages and red blood cells; a complex love story.

    Directory of Open Access Journals (Sweden)

    Djuna Zoe de Back

    2014-01-01

    Full Text Available Macrophages tightly control the production and clearance of red blood cells (RBC. During steady state haematopoiesis, approximately 1010 red blood cells are produced per hour within erythroblastic islands in humans. In these erythroblastic islands, resident bone marrow macrophages provide erythroblasts with interactions that are essential for erythroid development. New evidence suggests that not only under homeostasis but also under stress conditions, macrophages play an important role in promoting erythropoiesis. Once RBC have matured, these cells remain in circulation for about 120 days. At the end of their life span, RBC are cleared by macrophages residing in the spleen and the liver. Current theories about the removal of senescent RBC and the essential role of macrophages will be discussed as well as the role of macrophages in facilitating the removal of damaged cellular content from the RBC. In this review we will provide an overview on the role of macrophages in the regulation of RBC production, maintenance and clearance. In addition, we will discuss the interactions between these two cell types during transfer of immune complexes and pathogens from RBC to macrophages.

  20. Of macrophages and red blood cells; a complex love story.

    Science.gov (United States)

    de Back, Djuna Z; Kostova, Elena B; van Kraaij, Marian; van den Berg, Timo K; van Bruggen, Robin

    2014-01-01

    Macrophages tightly control the production and clearance of red blood cells (RBC). During steady state hematopoiesis, approximately 10(10) RBC are produced per hour within erythroblastic islands in humans. In these erythroblastic islands, resident bone marrow macrophages provide erythroblasts with interactions that are essential for erythroid development. New evidence suggests that not only under homeostasis but also under stress conditions, macrophages play an important role in promoting erythropoiesis. Once RBC have matured, these cells remain in circulation for about 120 days. At the end of their life span, RBC are cleared by macrophages residing in the spleen and the liver. Current theories about the removal of senescent RBC and the essential role of macrophages will be discussed as well as the role of macrophages in facilitating the removal of damaged cellular content from the RBC. In this review we will provide an overview on the role of macrophages in the regulation of RBC production, maintenance and clearance. In addition, we will discuss the interactions between these two cell types during transfer of immune complexes and pathogens from RBC to macrophages.

  1. Cytokine expression of macrophages in HIV-1-associated vacuolar myelopathy.

    Science.gov (United States)

    Tyor, W R; Glass, J D; Baumrind, N; McArthur, J C; Griffin, J W; Becker, P S; Griffin, D E

    1993-05-01

    Macrophages are frequently present within the periaxonal and intramyelinic vacuoles that are located primarily in the posterior and lateral funiculi of the thoracic spinal cord in HIV-associated vacuolar myelopathy. But the role of these macrophages in the formation of the vacuoles is unclear. One hypothesis is that cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF)-alpha, are produced locally by macrophages and have toxic effects on myelin or oligodendrocytes. The resulting myelin damage eventually culminates in the removal of myelin by macrophages and vacuole formation. We studied thoracic spinal cord specimens taken at autopsy from HIV-positive (+) and HIV-negative individuals. The predominant mononuclear cells present in HIV+ spinal cords are macrophages. They are located primarily in the posterior and lateral funiculi regardless of the presence or absence of vacuolar myelopathy. Macrophages and microglia are more frequent in HIV+ than HIV-negative individuals and these cells frequently stain for class I and class II antigens, IL-1, and TNF-alpha. Activated macrophages positive for IL-1 and TNF-alpha are great increased in the posterior and lateral funiculi of HIV+ individuals with and without vacuolar myelopathy, suggesting they are present prior to the development of vacuoles. Cytokines, such as TNF-alpha, may be toxic for myelin or oligodendrocytes, leading to myelin damage and removal by macrophages and vacuole formation.

  2. Selective phosphorylation during early macrophage differentiation

    KAUST Repository

    Zhang, Huoming

    2015-08-26

    The differentiation of macrophages from monocytes is a tightly controlled and complex biological process. Although numerous studies have been conducted using biochemical approaches or global gene/gene profiling, the mechanisms of the early stages of differentiation remain unclear. Here we used SILAC-based quantitative proteomics approach to perform temporal phosphoproteome profiling of early macrophage differentiation. We identified a large set of phosphoproteins and grouped them as PMA-regulated and non-regulated phosphoproteins in the early stages of differentiation. Further analysis of the PMA-regulated phosphoproteins revealed that transcriptional suppression, cytoskeletal reorganization and cell adhesion were among the most significantly activated pathways. Some key involved regulators of these pathways are mTOR, MYB, STAT1 and CTNNB. Moreover, we were able to classify the roles and activities of several transcriptional factors during different differentiation stages and found that E2F is likely to be an important regulator during the relatively late stages of differentiation. This study provides the first comprehensive picture of the dynamic phosphoproteome during myeloid cells differentiation, and identifies potential molecular targets in leukemic cells.

  3. Nanopatterned bulk metallic glass-based biomaterials modulate macrophage polarization.

    Science.gov (United States)

    Shayan, Mahdis; Padmanabhan, Jagannath; Morris, Aaron H; Cheung, Bettina; Smith, Ryan; Schroers, Jan; Kyriakides, Themis R

    2018-06-01

    Polarization of macrophages by chemical, topographical and mechanical cues presents a robust strategy for designing immunomodulatory biomaterials. Here, we studied the ability of nanopatterned bulk metallic glasses (BMGs), a new class of metallic biomaterials, to modulate murine macrophage polarization. Cytokine/chemokine analysis of IL-4 or IFNγ/LPS-stimulated macrophages showed that the secretion of TNF-α, IL-1α, IL-12, CCL-2 and CXCL1 was significantly reduced after 24-hour culture on BMGs with 55 nm nanorod arrays (BMG-55). Additionally, under these conditions, macrophages increased phagocytic potential and exhibited decreased cell area with multiple actin protrusions. These in vitro findings suggest that nanopatterning can modulate biochemical cues such as IFNγ/LPS. In vivo evaluation of the subcutaneous host response at 2 weeks demonstrated that the ratio of Arg-1 to iNOS increased in macrophages adjacent to BMG-55 implants, suggesting modulation of polarization. In addition, macrophage fusion and fibrous capsule thickness decreased and the number and size of blood vessels increased, which is consistent with changes in macrophage responses. Our study demonstrates that nanopatterning of BMG implants is a promising technique to selectively polarize macrophages to modulate the immune response, and also presents an effective tool to study mechanisms of macrophage polarization and function. Implanted biomaterials elicit a complex series of tissue and cellular responses, termed the foreign body response (FBR), that can be influenced by the polarization state of macrophages. Surface topography can influence polarization, which is broadly characterized as either inflammatory or repair-like. The latter has been linked to improved outcomes of the FBR. However, the impact of topography on macrophage polarization is not fully understood, in part, due to a lack of high moduli biomaterials that can be reproducibly processed at the nanoscale. Here, we studied

  4. Merge of terminological resources

    DEFF Research Database (Denmark)

    Henriksen, Lina; Braasch, Anna

    2012-01-01

    In our globalized world, the amount of cross-national communication increases rapidly, which also calls for easy access to multi-lingual high quality terminological resources. Sharing of terminology resources is currently becoming common practice, and efficient strategies for integration...... – or merging – of terminology resources are strongly needed. This paper discusses prerequisites for successful merging with the focus on identification of candidate duplicates of a subject domain found in the resources to be merged, and it describes automatic merging strategies to be applied to such duplicates...... in electronic terminology resources. Further, some perspectives of manual, supplementary assessment methods supporting the automatic procedures are sketched. Our considerations are primarily based on experience gained in the IATE and EuroTermBank projects, as merging was a much discussed issue in both projects....

  5. Renewable energy resources

    DEFF Research Database (Denmark)

    Ellabban, Omar S.; Abu-Rub, Haitham A.; Blaabjerg, Frede

    2014-01-01

    Electric energy security is essential, yet the high cost and limited sources of fossil fuels, in addition to the need to reduce greenhouse gasses emission, have made renewable resources attractive in world energy-based economies. The potential for renewable energy resources is enormous because...... they can, in principle, exponentially exceed the world's energy demand; therefore, these types of resources will have a significant share in the future global energy portfolio, much of which is now concentrating on advancing their pool of renewable energy resources. Accordingly, this paper presents how...... renewable energy resources are currently being used, scientific developments to improve their use, their future prospects, and their deployment. Additionally, the paper represents the impact of power electronics and smart grid technologies that can enable the proportionate share of renewable energy...

  6. Therapeutic potential of carbohydrates as regulators of macrophage activation.

    Science.gov (United States)

    Lundahl, Mimmi L E; Scanlan, Eoin M; Lavelle, Ed C

    2017-12-15

    It is well established for a broad range of disease states, including cancer and Mycobacterium tuberculosis infection, that pathogenesis is bolstered by polarisation of macrophages towards an anti-inflammatory phenotype, known as M2. As these innate immune cells are relatively long-lived, their re-polarisation to pro-inflammatory, phagocytic and bactericidal "classically activated" M1 macrophages is an attractive therapeutic approach. On the other hand, there are scenarios where the resolving inflammation, wound healing and tissue remodelling properties of M2 macrophages are beneficial - for example the successful introduction of biomedical implants. Although there are numerous endogenous and exogenous factors that have an impact on the macrophage polarisation spectrum, this review will focus specifically on prominent macrophage-modulating carbohydrate motifs with a view towards highlighting structure-function relationships and therapeutic potential. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Macrophages recognize size and shape of their targets.

    Directory of Open Access Journals (Sweden)

    Nishit Doshi

    2010-04-01

    Full Text Available Recognition by macrophages is a key process in generating immune response against invading pathogens. Previous studies have focused on recognition of pathogens through surface receptors present on the macrophage's surface. Here, using polymeric particles of different geometries that represent the size and shape range of a variety of bacteria, the importance of target geometry in recognition was investigated. The studies reported here reveal that attachment of particles of different geometries to macrophages exhibits a strong dependence on size and shape. For all sizes and shapes studied, particles possessing the longest dimension in the range of 2-3 microm exhibited highest attachment. This also happens to be the size range of most commonly found bacteria in nature. The surface features of macrophages, in particular the membrane ruffles, might play an important role in this geometry-based target recognition by macrophages. These findings have significant implications in understanding the pathogenicity of bacteria and in designing drug delivery carriers.

  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. Engineering mechanical microenvironment of macrophage and its biomedical applications.

    Science.gov (United States)

    Li, Jing; Li, Yuhui; Gao, Bin; Qin, Chuanguang; He, Yining; Xu, Feng; Yang, Hui; Lin, Min

    2018-03-01

    Macrophages are the most plastic cells in the hematopoietic system and can be widely found in almost all tissues. Recently studies have shown that mechanical cues (e.g., matrix stiffness and stress/strain) can significantly affect macrophage behaviors. Although existing reviews on the physical and mechanical cues that regulate the macrophage's phenotype are available, engineering mechanical microenvironment of macrophages in vitro as well as a comprehensive overview and prospects for their biomedical applications (e.g., tissue engineering and immunotherapy) has yet to be summarized. Thus, this review provides an overview on the existing methods for engineering mechanical microenvironment of macrophages in vitro and then a section on their biomedical applications and further perspectives are presented.

  10. Effect of Surface Modification and Macrophage Phenotype on Particle Internalization

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Daniel [Iowa State University; Phan, Ngoc [Iowa State University; Isely, Christopher [Iowa State University; Bruene, Lucas [Iowa State University; Bratlie, Kaitlin M [Ames Laboratory

    2014-11-10

    Material properties play a key role in the cellular internalization of polymeric particles. In the present study, we have investigated the effects of material characteristics such as water contact angle, zeta potential, melting temperature, and alternative activation of complement on particle internalization for pro-inflammatory, pro-angiogenic, and naïve macrophages by using biopolymers (~600 nm), functionalized with 13 different molecules. Understanding how material parameters influence particle internalization for different macrophage phenotypes is important for targeted delivery to specific cell populations. Here, we demonstrate that material parameters affect the alternative pathway of complement activation as well as particle internalization for different macrophage phenotypes. Here, we show that the quantitative structure–activity relationship method (QSAR) previously used to predict physiochemical properties of materials can be applied to targeting different macrophage phenotypes. These findings demonstrated that targeted drug delivery to macrophages could be achieved by exploiting material parameters.

  11. Macrophages Contribute to the Spermatogonial Niche in the Adult Testis

    Directory of Open Access Journals (Sweden)

    Tony DeFalco

    2015-08-01

    Full Text Available The testis produces sperm throughout the male reproductive lifespan by balancing self-renewal and differentiation of spermatogonial stem cells (SSCs. Part of the SSC niche is thought to lie outside the seminiferous tubules of the testis; however, specific interstitial components of the niche that regulate spermatogonial divisions and differentiation remain undefined. We identified distinct populations of testicular macrophages, one of which lies on the surface of seminiferous tubules, in close apposition to areas of tubules enriched for undifferentiated spermatogonia. These macrophages express spermatogonial proliferation- and differentiation-inducing factors, such as colony-stimulating factor 1 (CSF1 and enzymes involved in retinoic acid (RA biosynthesis. We show that transient depletion of macrophages leads to a disruption in spermatogonial differentiation. These findings reveal an unexpected role for macrophages in the spermatogonial niche in the testis and raise the possibility that macrophages play previously unappreciated roles in stem/progenitor cell regulation in other tissues.

  12. Mertk deficiency affects macrophage directional migration via disruption of cytoskeletal organization.

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    Yong Tang

    Full Text Available Mertk belongs to the Tyro3, Axl and Mertk (TAM family of receptor tyrosine kinases, and plays a pivotal role in regulation of cytoskeletal rearrangement during phagocytosis. Phagocytosis by either professional or non-professional phagocytes is impaired in the Mertk deficient individual. In the present study, we further investigated the effects of Mertk mutation on peritoneal macrophage morphology, attachment, spreading and movement. Mertk-mutated macrophages exhibited decreased attachment, weak spreading, loss of spindle-like body shape and lack of clear leading and trailing edges within the first few hours of culture, as observed by environmental scanning electron microscopy. Time-lapse video photography recording showed that macrophage without Mertk conducted mainly random movement with oscillating swing around the cell body, and lost the directional migration action seen on the WT cells. Western blotting showed a decreased phosphorylation of focal adhesion kinase (FAK. Immunocytochemistry revealed that actin filaments and dynamic protein myosin II failed to concentrate in the leading edge of migrating cells. Microtubules were localized mainly in one side of mutant cell body, with no clear MTOC and associated radially-distributed microtubule bundles, which were clearly evident in the WT cells. Our results suggest that Mertk deficiency affects not only phagocytosis but also cell shape and migration, likely through a common regulatory mechanism on cytoskeletons.

  13. Functional expression of P2X family receptors in macrophages is affected by microenvironment in mouse T cell acute lymphoblastic leukemia

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    Chen, Shayan; Feng, Wenli; Yang, Xiao; Yang, Wanzhu; Ru, Yongxin; Liao, Jinfeng; Wang, Lina; Lin, Yongmin; Ren, Qian [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020 (China); Zheng, Guoguang, E-mail: zhengggtjchn@aliyun.com [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020 (China); Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Beijing 100730 (China)

    2014-04-18

    Highlights: • We study the impact of leukemic microenvironment on P2X family receptors in Mφs. • Bone marrow and spleen Mφs are studied in Notch1-induced mouse leukemia model. • Increased expression of P2X7R is found in Mφs during the development of leukemia. • Elevated P2X7R-mediated calcium response is found in Mφs at late stage of leukemia. • More apoptotic Mφs are found in bone marrow and spleen at late stage of leukemia. - Abstract: Nucleotides are important players in intercellular signaling communication network. P2X family receptors (P2XRs) are ATP-gated plasma membrane ion channels with diverse biological functions. Macrophages are important components in the microenvironment of hematopoiesis participating in both physiological and pathological processes. However, the role of P2XRs in macrophages in leukemia has not been established. Here we investigated expression pattern and functions of P2XRs in macrophages from bone marrow (BM) and spleen of Notch1-induced T-ALL mice. Real-time PCR showed that P2XRs except P2X5R were expressed in BM and spleen macrophages. Furthermore, with the development of leukemia, the expression of P2X7R increased in both BM and spleen macrophages whereas expression of P2X1R increased in spleen macrophages. Live cell imaging recoding the Ca{sup 2+} response demonstrated that P2X7R expressed in macrophages was functional. TUNEL and electron microscopy analysis found that apoptotic macrophages were frequently observed in BM and spleen at late stage of leukemia, which was partly contributed by the activation of overexpressed P2X7R. Our results suggested that the intercellular communication mediated by nucleotides might orchestrate in the pathological process of leukemia and could be a potential target for the treatment of leukemia.

  14. Functional expression of P2X family receptors in macrophages is affected by microenvironment in mouse T cell acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Chen, Shayan; Feng, Wenli; Yang, Xiao; Yang, Wanzhu; Ru, Yongxin; Liao, Jinfeng; Wang, Lina; Lin, Yongmin; Ren, Qian; Zheng, Guoguang

    2014-01-01

    Highlights: • We study the impact of leukemic microenvironment on P2X family receptors in Mφs. • Bone marrow and spleen Mφs are studied in Notch1-induced mouse leukemia model. • Increased expression of P2X7R is found in Mφs during the development of leukemia. • Elevated P2X7R-mediated calcium response is found in Mφs at late stage of leukemia. • More apoptotic Mφs are found in bone marrow and spleen at late stage of leukemia. - Abstract: Nucleotides are important players in intercellular signaling communication network. P2X family receptors (P2XRs) are ATP-gated plasma membrane ion channels with diverse biological functions. Macrophages are important components in the microenvironment of hematopoiesis participating in both physiological and pathological processes. However, the role of P2XRs in macrophages in leukemia has not been established. Here we investigated expression pattern and functions of P2XRs in macrophages from bone marrow (BM) and spleen of Notch1-induced T-ALL mice. Real-time PCR showed that P2XRs except P2X5R were expressed in BM and spleen macrophages. Furthermore, with the development of leukemia, the expression of P2X7R increased in both BM and spleen macrophages whereas expression of P2X1R increased in spleen macrophages. Live cell imaging recoding the Ca 2+ response demonstrated that P2X7R expressed in macrophages was functional. TUNEL and electron microscopy analysis found that apoptotic macrophages were frequently observed in BM and spleen at late stage of leukemia, which was partly contributed by the activation of overexpressed P2X7R. Our results suggested that the intercellular communication mediated by nucleotides might orchestrate in the pathological process of leukemia and could be a potential target for the treatment of leukemia

  15. MicroRNA-20a inhibits autophagic process by targeting ATG7 and ATG16L1 and favors mycobacterial survival in macrophage cells.

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    Le Guo

    2016-10-01

    Full Text Available Autophagy plays important roles in the host immune response against mycobacterial infection. Mycobacterium tuberculosis (M. tuberculosis can live in macrophages owing to its ability to evade attacks by regulating autophagic response. MicroRNAs (miRNAs are small noncoding, endogenously encoded RNA which plays critical roles in precise regulation of macrophage functions. Whether miRNAs specifically influence the activation of macrophage autophagy during M. tuberculosis infection are largely unknown. In this study, we demonstrate that BCG infection of macrophages resulted in enhanced expression of miRNA-20a, which inhibits autophagic process by targeting ATG7 and ATG16L1 and promotes BCG survival in macrophages. Forced overexpression of miR-20a decreased the expression levels of LC3-II and the number of LC3 puncta in macrophages, and promoted BCG survival in macrophages, while transfection with miR-20a inhibitor had the opposite effect. Moreover, the inhibitory effect of miR-20a on autophagy was further confimed by transmission electron microscopy (TEM analysis. Quantification of autophagosomes per cellular cross-section revealed a significant reduction upon transfection with miR-20a mimic, but transfection with miR-20a inhibitor increased the number of autophagosomes per cellular cross-section. Moreover, silencing of ATG7 significantly inhibited autophagic response, and transfection with ATG7 siRNA plus miR-20a mimic could further decrease autophagic response. Collectively, our data reveal that miR-20a inhibits autophagic response and promotes BCG survival in macrophages by targeting ATG7 and ATG16L1, which may have implications for a better understanding of pathogenesis of M. tuberculosis infection.

  16. microRNA-20a Inhibits Autophagic Process by Targeting ATG7 and ATG16L1 and Favors Mycobacterial Survival in Macrophage Cells.

    Science.gov (United States)

    Guo, Le; Zhao, Jin; Qu, Yuliang; Yin, Runting; Gao, Qian; Ding, Shuqin; Zhang, Ying; Wei, Jun; Xu, Guangxian

    2016-01-01

    Autophagy plays important roles in the host immune response against mycobacterial infection. Mycobacterium tuberculosis ( M. tuberculosis ) can live in macrophages owing to its ability to evade attacks by regulating autophagic response. MicroRNAs (miRNAs) are small noncoding, endogenously encoded RNA which plays critical roles in precise regulation of macrophage functions. Whether miRNAs specifically influence the activation of macrophage autophagy during M. tuberculosis infection are largely unknown. In this study, we demonstrate that BCG infection of macrophages resulted in enhanced expression of miRNA-20a, which inhibits autophagic process by targeting ATG7 and ATG16L1 and promotes BCG survival in macrophages. Forced overexpression of miR-20a decreased the expression levels of LC3-II and the number of LC3 puncta in macrophages, and promoted BCG survival in macrophages, while transfection with miR-20a inhibitor had the opposite effect. Moreover, the inhibitory effect of miR-20a on autophagy was further confirmed by transmission electron microscopy (TEM) analysis. Quantification of autophagosomes per cellular cross-section revealed a significant reduction upon transfection with miR-20a mimic, but transfection with miR-20a inhibitor increased the number of autophagosomes per cellular cross-section. Moreover, silencing of ATG7 significantly inhibited autophagic response, and transfection with ATG7 siRNA plus miR-20a mimic could further decrease autophagic response. Collectively, our data reveal that miR-20a inhibits autophagic response and promotes BCG survival in macrophages by targeting ATG7 and ATG16L1, which may have implications for a better understanding of pathogenesis of M. tuberculosis infection.

  17. Activated Macrophages as a Novel Determinant of Tumor Cell Radioresponse: The Role of Nitric Oxide-Mediated Inhibition of Cellular Respiration and Oxygen Sparing

    International Nuclear Information System (INIS)

    Jiang Heng; De Ridder, Mark; Verovski, Valeri N.; Sonveaux, Pierre; Jordan, Benedicte F.; Law, Kalun; Monsaert, Christinne; Van den Berge, Dirk L.; Verellen, Dirk; Feron, Olivier; Gallez, Bernard; Storme, Guy A.

    2010-01-01

    Purpose: Nitric oxide (NO), synthesized by the inducible nitric oxide synthase (iNOS), is known to inhibit metabolic oxygen consumption because of interference with mitochondrial respiratory activity. This study examined whether activation of iNOS (a) directly in tumor cells or (b) in bystander macrophages may improve radioresponse through sparing of oxygen. Methods and Materials: EMT-6 tumor cells and RAW 264.7 macrophages were exposed to bacterial lipopolysaccharide plus interferon-γ, and examined for iNOS expression by reverse transcription polymerase chain reaction, Western blotting and enzymatic activity. Tumor cells alone, or combined with macrophages were subjected to metabolic hypoxia and analyzed for radiosensitivity by clonogenic assay, and for oxygen consumption by electron paramagnetic resonance and a Clark-type electrode. Results: Both tumor cells and macrophages displayed a coherent picture of iNOS induction at transcriptional/translational levels and NO/nitrite production, whereas macrophages showed also co-induction of the inducible heme oxygenase-1, which is associated with carbon monoxide (CO) and bilirubin production. Activation of iNOS in tumor cells resulted in a profound oxygen sparing and a 2.3-fold radiosensitization. Bystander NO-producing, but not CO-producing, macrophages were able to block oxygen consumption by 1.9-fold and to radiosensitize tumor cells by 2.2-fold. Both effects could be neutralized by aminoguanidine, a metabolic iNOS inhibitor. An improved radioresponse was clearly observed at macrophages to tumor cells ratios ranging between 1:16 to 1:1. Conclusions: Our study is the first, as far as we are aware, to provide evidence that iNOS may induce radiosensitization through oxygen sparing, and illuminates NO-producing macrophages as a novel determinant of tumor cell radioresponse within the hypoxic tumor microenvironment.

  18. DMPD: Differential responses of human monocytes and macrophages to IL-4 and IL-13. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10534111 Differential responses of human monocytes and macrophages to IL-4 and IL-1...):575-8. (.png) (.svg) (.html) (.csml) Show Differential responses of human monocytes and macrophages to IL-...4 and IL-13. PubmedID 10534111 Title Differential responses of human monocytes an

  19. DMPD: Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12960231 Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited sign...82. Epub 2003 Jul 22. (.png) (.svg) (.html) (.csml) Show Macrophage activation through CCR5- and CXCR4-media...on through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. Authors Lee C, Liu QH, Tomkowicz B, Yi

  20. DMPD: Mechanisms for the anti-inflammatory effects of adiponectin in macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18336664 Mechanisms for the anti-inflammatory effects of adiponectin in macrophages...(.html) (.csml) Show Mechanisms for the anti-inflammatory effects of adiponectin in macrophages. PubmedID 18...336664 Title Mechanisms for the anti-inflammatory effects of adiponectin in macro

  1. EFFECTIVE ELECTRONIC TUTORIAL

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    Andrei A. Fedoseev

    2014-01-01

    Full Text Available The article analyzes effective electronic tutorials creation and application based on the theory of pedagogy. Herewith the issues of necessary electronic tutorial functional, ways of the educational process organization with the use of information and communication technologies and the logistics of electronic educational resources are touched upon. 

  2. Effect of particle size on hydroxyapatite crystal-induced tumor necrosis factor alpha secretion by macrophages.

    Science.gov (United States)

    Nadra, Imad; Boccaccini, Aldo R; Philippidis, Pandelis; Whelan, Linda C; McCarthy, Geraldine M; Haskard, Dorian O; Landis, R Clive

    2008-01-01

    Macrophages may promote a vicious cycle of inflammation and calcification in the vessel wall by ingesting neointimal calcific deposits (predominantly hydroxyapatite) and secreting tumor necrosis factor (TNF)alpha, itself a vascular calcifying agent. Here we have investigated whether particle size affects the proinflammatory potential of hydroxyapatite crystals in vitro and whether the nuclear factor (NF)-kappaB pathway plays a role in the macrophage TNFalpha response. The particle size and nano-topography of nine different crystal preparations was analyzed by X-ray diffraction, Raman spectroscopy, scanning electron microscopy and gas sorbtion analysis. Macrophage TNFalpha secretion was inversely related to hydroxyapatite particle size (P=0.011, Spearman rank correlation test) and surface pore size (P=0.014). A necessary role for the NF-kappaB pathway was demonstrated by time-dependent I kappaB alpha degradation and sensitivity to inhibitors of I kappaB alpha degradation. To test whether smaller particles were intrinsically more bioactive, their mitogenic activity on fibroblast proliferation was examined. This showed close correlation between TNFalpha secretion and crystal-induced fibroblast proliferation (P=0.007). In conclusion, the ability of hydroxyapatite crystals to stimulate macrophage TNFalpha secretion depends on NF-kappaB activation and is inversely related to particle and pore size, with crystals of 1-2 microm diameter and pore size of 10-50 A the most bioactive. Microscopic calcific deposits in early stages of atherosclerosis may therefore pose a greater inflammatory risk to the plaque than macroscopically or radiologically visible deposits in more advanced lesions.

  3. SIRT2 ameliorates lipopolysaccharide-induced inflammation in macrophages

    International Nuclear Information System (INIS)

    Lee, Ae Sin; Jung, Yu Jin; Kim, Dal; Nguyen-Thanh, Tung; Kang, Kyung Pyo; Lee, Sik; Park, Sung Kwang; Kim, Won

    2014-01-01

    Highlights: • Knockout of SIRT2 attenuates lipopolysaccharide-induced iNOS expression. • Lipopolysaccharide-induced NO production is decreased in SIRT2 KO macrophage. • SIRT2 deficiency suppresses lipopolysaccharide-induced ROS production in macrophage. • M1-macrophage related factors are decreased in SIRT2 deficient cells. • SIRT2 deficiency decreases lipopolysaccharide-induced activation of NFκB. - Abstract: Introduction: SIRT2 is a NAD(+)-dependent deacetylases and associated with numerous processes such as infection, carcinogenesis, DNA damage and cell cycle regulation. However, the role of SIRT2 in inflammatory process in macrophage remains unclear. Materials and methods: In the present study, we have evaluated the regulatory effects of SIRT2 in lipopolysaccharide (LPS)-stimulated macrophages isolated from SIRT2 knockout (KO) and wild type (WT) mice or Raw264.7 macrophage cells. As inflammatory parameters, expression of inducible nitric oxide synthase (iNOS), the productions of nitric oxide, reactive oxygen species (ROS) and M1-macrophage-related factors were evaluated. We also examined the effects of SIRT2 on activation of nuclear factor-kappaB (NFκB) signaling. Results: SIRT2 deficiency inhibits LPS-induced iNOS mRNA and protein expression in bone marrow derived macrophages. SIRT2-siRNA transfection also suppressed LPS-induced iNOS expression in Raw264.7 macrophage cells. Bone marrow derived macrophages isolated from SIRT2 KO mice produced lower nitric oxide and expressed lower levels of M1-macrophage related markers including iNOS and CD86 in response to LPS than WT mice. Decrease of SIRT2 reduced the LPS-induced reactive oxygen species production. Deficiency of SIRT2 resulted in inhibition of NFκB activation through reducing the phosphorylation and degradation of IκBα. The phosphorylation and nuclear translocation of p65 was significantly decreased in SIRT2-deficient macrophages after LPS stimulation. Discussion: Our data suggested that

  4. SIRT2 ameliorates lipopolysaccharide-induced inflammation in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ae Sin; Jung, Yu Jin; Kim, Dal; Nguyen-Thanh, Tung [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kang, Kyung Pyo [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Lee, Sik [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Park, Sung Kwang [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Kim, Won, E-mail: kwon@jbnu.ac.kr [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of)

    2014-08-08

    Highlights: • Knockout of SIRT2 attenuates lipopolysaccharide-induced iNOS expression. • Lipopolysaccharide-induced NO production is decreased in SIRT2 KO macrophage. • SIRT2 deficiency suppresses lipopolysaccharide-induced ROS production in macrophage. • M1-macrophage related factors are decreased in SIRT2 deficient cells. • SIRT2 deficiency decreases lipopolysaccharide-induced activation of NFκB. - Abstract: Introduction: SIRT2 is a NAD(+)-dependent deacetylases and associated with numerous processes such as infection, carcinogenesis, DNA damage and cell cycle regulation. However, the role of SIRT2 in inflammatory process in macrophage remains unclear. Materials and methods: In the present study, we have evaluated the regulatory effects of SIRT2 in lipopolysaccharide (LPS)-stimulated macrophages isolated from SIRT2 knockout (KO) and wild type (WT) mice or Raw264.7 macrophage cells. As inflammatory parameters, expression of inducible nitric oxide synthase (iNOS), the productions of nitric oxide, reactive oxygen species (ROS) and M1-macrophage-related factors were evaluated. We also examined the effects of SIRT2 on activation of nuclear factor-kappaB (NFκB) signaling. Results: SIRT2 deficiency inhibits LPS-induced iNOS mRNA and protein expression in bone marrow derived macrophages. SIRT2-siRNA transfection also suppressed LPS-induced iNOS expression in Raw264.7 macrophage cells. Bone marrow derived macrophages isolated from SIRT2 KO mice produced lower nitric oxide and expressed lower levels of M1-macrophage related markers including iNOS and CD86 in response to LPS than WT mice. Decrease of SIRT2 reduced the LPS-induced reactive oxygen species production. Deficiency of SIRT2 resulted in inhibition of NFκB activation through reducing the phosphorylation and degradation of IκBα. The phosphorylation and nuclear translocation of p65 was significantly decreased in SIRT2-deficient macrophages after LPS stimulation. Discussion: Our data suggested that

  5. The influence of macrophage growth factors on Theiler's Murine Encephalomyelitis Virus (TMEV) infection and activation of macrophages.

    Science.gov (United States)

    Schneider, Karin M; Watson, Neva B; Minchenberg, Scott B; Massa, Paul T

    2018-02-01

    Macrophages are common targets for infection and innate immune activation by many pathogenic viruses including the neurotropic Theiler's Murine Encephalomyelitis Virus (TMEV). As both infection and innate activation of macrophages are key determinants of viral pathogenesis especially in the central nervous system (CNS), an analysis of macrophage growth factors on these events was performed. C3H mouse bone-marrow cells were differentiated in culture using either recombinant macrophage colony stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF), inoculated with TMEV (BeAn) and analyzed at various times thereafter. Cytokine RNA and protein analysis, virus titers, and flow cytometry were performed to characterize virological parameters under these culture conditions. GM-CSF-differentiated macrophages showed higher levels of TMEV viral RNA and proinflammatory molecules compared to infected M-CSF-differentiated cells. Thus, GM-CSF increases both TMEV infection and TMEV-induced activation of macrophages compared to that seen with M-CSF. Moreover, while infectious viral particles decreased from a peak at 12h to undetectable levels at 48h post infection, TMEV viral RNA remained higher in GM-CSF- compared to M-CSF-differentiated macrophages in concert with increased proinflammatory gene expression. Analysis of a possible basis for these differences determined that glycolytic rates contributed to heightened virus replication and proinflammatory cytokine secretion in GM-CSF compared to M-CSF-differentiated macrophages. In conclusion, we provide evidence implicating a role for GM-CSF in promoting virus replication and proinflammatory cytokine expression in macrophages, indicating that GM-CSF may be a key factor for TMEV infection and the induction of chronic TMEV-induced immunopathogenesis in the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis.

    Science.gov (United States)

    Shaw, Catherine A; Webb, David J; Rossi, Adriano G; Megson, Ian L

    2009-05-07

    Nitric oxide (NO) can be both pro- and anti-apoptotic in various cell types, including macrophages. This apparent paradox may result from the actions of NO-related species generated in the microenvironment of the cell, for example the formation of peroxynitrite (ONOO-). In this study we have examined the ability of NO and ONOO- to evoke apoptosis in human monocyte-derived macrophages (MDMvarphi), and investigated whether preconditioning by cyclic guanosine monophosphate (cGMP) is able to limit apoptosis in this cell type. Characterisation of the NO-related species generated by (Z)-1- [2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA/NO) and 1,2,3,4-oxatriazolium, 5-amino-3-(3,4-dichlorophenyl)-, chloride (GEA-3162) was performed by electrochemistry using an isolated NO electrode and electron paramagnetic resonance (EPR) spectrometry. Mononuclear cells were isolated from peripheral blood of healthy volunteers and cultured to allow differentiation into MDMvarphi. Resultant MDMvarphi were treated for 24 h with DETA/NO (100 - 1000 muM) or GEA-3162 (10 - 300 muM) in the presence or absence of BAY 41-2272 (1 muM), isobutylmethylxanthine (IBMX; 1 muM), 1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 20 muM) or 8-bromo-cGMP (1 mM). Apoptosis in MDMvarphi was assessed by flow cytometric analysis of annexin V binding in combination with propidium iodide staining. Electrochemistry and EPR revealed that DETA/NO liberated free NO radical, whilst GEA-3162 concomitantly released NO and O2-, and is therefore a ONOO- generator. NO (DETA/NO) had no effect on cell viability, but ONOO- (GEA-3162) caused a concentration-dependent induction of apoptosis in MDMvarphi. Preconditioning of MDMvarphi with NO in combination with the phosphodiesterase inhibitor, 3-Isobutyl-1-methylxanthine (IBMX), or the NO-independent stimulator of soluble guanylate cyclase, BAY 41-2272, significantly attenuated ONOO--induced apoptosis in a cGMP-dependent manner. These results

  7. Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis

    Directory of Open Access Journals (Sweden)

    Rossi Adriano G

    2009-05-01

    Full Text Available Abstract Background Nitric oxide (NO can be both pro- and anti-apoptotic in various cell types, including macrophages. This apparent paradox may result from the actions of NO-related species generated in the microenvironment of the cell, for example the formation of peroxynitrite (ONOO-. In this study we have examined the ability of NO and ONOO- to evoke apoptosis in human monocyte-derived macrophages (MDMϕ, and investigated whether preconditioning by cyclic guanosine monophosphate (cGMP is able to limit apoptosis in this cell type. Methods Characterisation of the NO-related species generated by (Z-1- [2-(2-aminoethyl-N-(2-ammonioethylamino]diazen-1-ium-1,2-diolate (DETA/NO and 1,2,3,4-oxatriazolium, 5-amino-3-(3,4-dichlorophenyl-, chloride (GEA-3162 was performed by electrochemistry using an isolated NO electrode and electron paramagnetic resonance (EPR spectrometry. Mononuclear cells were isolated from peripheral blood of healthy volunteers and cultured to allow differentiation into MDMϕ. Resultant MDMϕ were treated for 24 h with DETA/NO (100 – 1000 μM or GEA-3162 (10 – 300 μM in the presence or absence of BAY 41–2272 (1 μM, isobutylmethylxanthine (IBMX; 1 μM, 1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 20 μM or 8-bromo-cGMP (1 mM. Apoptosis in MDMϕ was assessed by flow cytometric analysis of annexin V binding in combination with propidium iodide staining. Results Electrochemistry and EPR revealed that DETA/NO liberated free NO radical, whilst GEA-3162 concomitantly released NO and O2-, and is therefore a ONOO- generator. NO (DETA/NO had no effect on cell viability, but ONOO- (GEA-3162 caused a concentration-dependent induction of apoptosis in MDMϕ. Preconditioning of MDMϕ with NO in combination with the phosphodiesterase inhibitor, 3-Isobutyl-1-methylxanthine (IBMX, or the NO-independent stimulator of soluble guanylate cyclase, BAY 41–2272, significantly attenuated ONOO--induced apoptosis in a cGMP-dependent manner

  8. Soluble human leukocyte antigen G5 polarizes differentiation of macrophages toward a decidual macrophage-like phenotype.

    Science.gov (United States)

    Lee, Cheuk-Lun; Guo, YiFan; So, Kam-Hei; Vijayan, Madhavi; Guo, Yue; Wong, Vera H H; Yao, YuanQing; Lee, Kai-Fai; Chiu, Philip C N; Yeung, William S B

    2015-10-01

    What are the actions of soluble human leukocyte antigen G5 (sHLAG5) on macrophage differentiation? sHLAG5 polarizes the differentiation of macrophages toward a decidual macrophage-like phenotype, which could regulate fetomaternal tolerance and placental development. sHLAG5 is a full-length soluble isoform of human leukocyte antigen implicated in immune tolerance during pregnancy. Low or undetectable circulating level of sHLAG5 in first trimester of pregnancy is associated with pregnancy complications such as pre-eclampsia and spontaneous abortion. Decidual macrophages are located in close proximity to invasive trophoblasts, and are involved in regulating fetomaternal tolerance and placental development. Human peripheral blood monocytes were differentiated into macrophages by treatment with granulocyte macrophage colony-stimulating factor in the presence or absence of recombinant sHLAG5 during the differentiation process. The phenotypes and the biological activities of the resulting macrophages were compared. Recombinant sHLAG5 was produced in Escherichia coli BL21 and the protein identity was verified by tandem mass spectrometry. The expression of macrophage markers were analyzed by flow cytometry and quantitative PCR. Phagocytosis was determined by flow cytometry. Indoleamine 2,3-dioxygenase 1 expression and activity were measured by western blot analysis and kynurenine assay, respectively. Cell proliferation and cell cycling were determined by fluorometric cell proliferation assay and flow cytometry, respectively. Cytokine secretion was determined by cytokine array and ELISA kits. Intracellular cytokine expression was measured by flow cytometry. Cell invasion and migration were determined by trans-well invasion and migration assay, respectively. sHLAG5 drove the differentiation of macrophages with 'immuno-modulatory' characteristics, including reduced expression of M1 macrophage marker CD86 and increased expression of M2 macrophage marker CD163. sHLAG5-polarized

  9. Macrophage Phenotypes Regulate Scar Formation and Chronic Wound Healing.

    Science.gov (United States)

    Hesketh, Mark; Sahin, Katherine B; West, Zoe E; Murray, Rachael Z

    2017-07-17

    Macrophages and inflammation play a beneficial role during wound repair with macrophages regulating a wide range of processes, such as removal of dead cells, debris and pathogens, through to extracellular matrix deposition re-vascularisation and wound re-epithelialisation. To perform this range of functions, these cells develop distinct phenotypes over the course of wound healing. They can present with a pro-inflammatory M1 phenotype, more often found in the early stages of repair, through to anti-inflammatory M2 phenotypes that are pro-repair in the latter stages of wound healing. There is a continuum of phenotypes between these ranges with some cells sharing phenotypes of both M1 and M2 macrophages. One of the less pleasant consequences of quick closure, namely the replacement with scar tissue, is also regulated by macrophages, through their promotion of fibroblast proliferation, myofibroblast differentiation and collagen deposition. Alterations in macrophage number and phenotype disrupt this process and can dictate the level of scar formation. It is also clear that dysregulated inflammation and altered macrophage phenotypes are responsible for hindering closure of chronic wounds. The review will discuss our current knowledge of macrophage phenotype on the repair process and how alterations in the phenotypes might alter wound closure and the final repair quality.

  10. Effects of microparticle size and Fc density on macrophage phagocytosis.

    Directory of Open Access Journals (Sweden)

    Patricia Pacheco

    Full Text Available Controlled induction of phagocytosis in macrophages offers the ability to therapeutically regulate the immune system as well as improve delivery of chemicals or biologicals for immune processing. Maximizing particle uptake by macrophages through Fc receptor-mediated phagocytosis could lead to new delivery mechanisms in drug or vaccine development. Fc ligand density and particle size were examined independently and in combination in order to optimize and tune the phagocytosis of opsonized microparticles. We show the internalization efficiency of small polystyrene particles (0.5 µm to 2 µm is significantly affected by changes in Fc ligand density, while particles greater than 2 µm show little correlation between internalization and Fc density. We found that while macrophages can efficiently phagocytose a large number of smaller particles, the total volume of phagocytosed particles is maximized through the non-specific uptake of larger microparticles. Therefore, larger microparticles may be more efficient at delivering a greater therapeutic payload to macrophages, but smaller opsonized microparticles can deliver bio-active substances to a greater percentage of the macrophage population. This study is the first to treat as independent variables the physical and biological properties of Fc density and microparticle size that initiate macrophage phagocytosis. Defining the physical and biological parameters that affect phagocytosis efficiency will lead to improved methods of microparticle delivery to macrophages.

  11. Influence of Macrophages on the Rooster Spermatozoa Quality.

    Science.gov (United States)

    Kuzelova, L; Vasicek, J; Chrenek, P

    2015-08-01

    The goal of this study was to evaluate the occurrence of macrophages in rooster semen and to investigate their impact on the spermatozoa quality. Ross 308 breeder males (n = 30) with no evidence of genital tract infections were used to determine the concentration of macrophages using fluorescently conjugated acetylated low-density lipoprotein (AcLDL). Subsequently, the roosters were divided into two groups on the basis of semen macrophage concentration, and semen quality was compared in two heterospermic samples. We applied computer-assisted semen analysis (CASA) system to determine motility parameters. Fluorescence microscopy and flow cytometry were used to evaluate occurrence of apoptotic and dead spermatozoa. Spermatozoa fertility potential was examined after intravaginal artificial insemination of hens. Eighteen roosters (control group) contained 0.2-3% of macrophages within spermatozoa population and ten roosters (macrophage group) had 10-15% of macrophages. Males from macrophage group had lower (p rooster semen may have a negative effect on some parameters of rooster spermatozoa evaluated in vitro. Furthermore, our study suggests that flow cytometry allows more precise examination of spermatozoa viability and apoptosis in a very short time compared with the fluorescent microscopy. © 2015 Blackwell Verlag GmbH.

  12. Effects of lipopolysaccharide on the catabolic activity of macrophages

    International Nuclear Information System (INIS)

    Cluff, C.; Ziegler, H.K.

    1986-01-01

    The ability of macrophages to degrade and catabolize antigens is of relevance both as a means to process complex antigens prior to presentation to T cells, as well as a way to down regulate immune responses by destroying the antigenicity of polypeptides. With these considerations, the authors have investigated the regulation of macrophage catabolic activity by lipopolysaccharide (LPS). Catabolic activity was quantitated by following the distribution and molecular form of 125 -I labelled surface components of heat-killed Listeria monocytogenes (HKLM) subsequent to their uptake by macrophages. They have compared the catabolic activity of macrophages from peritoneal exudates of mice injected i.p. with saline or LPS and have found that LPS-elicited macrophages display a greatly enhanced (3 fold) rate of catabolism. This increase in catabolic activity peaks 3 days after LPS injection and steadily declines thereafter, approaching a baseline level after 3 weeks. The enhancement of catabolic activity is under LPS gene control. LPS-elicited macrophages rapidly destroy the antigenicity of bacterial antigens and function poorly as antigen presenting cells in vitro. These results suggest that LPS elicits a macrophage population specialized for antigen degradation functions with negative regulatory effects on the induction of specific immune responses

  13. Unique proteomic signatures distinguish macrophages and dendritic cells.

    Directory of Open Access Journals (Sweden)

    Lev Becker

    Full Text Available Monocytes differentiate into heterogeneous populations of tissue macrophages and dendritic cells (DCs that regulate inflammation and immunity. Identifying specific populations of myeloid cells in vivo is problematic, however, because only a limited number of proteins have been used to assign cellular phenotype. Using mass spectrometry and bone marrow-derived cells, we provided a global view of the proteomes of M-CSF-derived macrophages, classically and alternatively activated macrophages, and GM-CSF-derived DCs. Remarkably, the expression levels of half the plasma membrane proteins differed significantly in the various populations of cells derived in vitro. Moreover, the membrane proteomes of macrophages and DCs were more distinct than those of classically and alternatively activated macrophages. Hierarchical cluster and dual statistical analyses demonstrated that each cell type exhibited a robust proteomic signature that was unique. To interrogate the phenotype of myeloid cells in vivo, we subjected elicited peritoneal macrophages harvested from wild-type and GM-CSF-deficient mice to mass spectrometric and functional analysis. Unexpectedly, we found that peritoneal macrophages exhibited many features of the DCs generated in vitro. These findings demonstrate that global analysis of the membrane proteome can help define immune cell phenotypes in vivo.

  14. 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.

  15. Ginger extract inhibits LPS induced macrophage activation and function

    Directory of Open Access Journals (Sweden)

    Bruch David

    2008-01-01

    Full Text Available Abstract Background Macrophages play a dual role in host defence. They act as the first line of defence by mounting an inflammatory response to antigen exposure and also act as antigen presenting cells and initiate the adaptive immune response. They are also the primary infiltrating cells at the site of inflammation. Inhibition of macrophage activation is one of the possible approaches towards modulating inflammation. Both conventional and alternative approaches are being studied in this regard. Ginger, an herbal product with broad anti inflammatory actions, is used as an alternative medicine in a number of inflammatory conditions like rheumatic disorders. In the present study we examined the effect of ginger extract on macrophage activation in the presence of LPS stimulation. Methods Murine peritoneal macrophages were stimulated by LPS in presence or absence of ginger extract and production of proinflammatory cytokines and chemokines were observed. We also studied the effect of ginger extract on the LPS induced expression of MHC II, B7.1, B7.2 and CD40 molecules. We also studied the antigen presenting function of ginger extract treated macrophages by primary mixed lymphocyte reaction. Results We observed that ginger extract inhibited IL-12, TNF-α, IL-1β (pro inflammatory cytokines and RANTES, MCP-1 (pro inflammatory chemokines production in LPS stimulated macrophages. Ginger extract also down regulated the expression of B7.1, B7.2 and MHC class II molecules. In addition ginger extract negatively affected the antigen presenting function of macrophages and we observed a significant reduction in T cell proliferation in response to allostimulation, when ginger extract treated macrophages were used as APCs. A significant decrease in IFN-γ and IL-2 production by T cells in response to allostimulation was also observed. Conclusion In conclusion ginger extract inhibits macrophage activation and APC function and indirectly inhibits T cell activation.

  16. Rhinovirus infection induces distinct transcriptome profiles in polarized human macrophages.

    Science.gov (United States)

    Rajput, Charu; Walsh, Megan P; Eder, Breanna N; Metitiri, Ediri E; Popova, Antonia P; Hershenson, Marc B

    2018-05-01

    Infections with rhinovirus (RV) cause asthma exacerbations. Recent studies suggest that macrophages play a role in asthmatic airway inflammation and the innate immune response to RV infection. Macrophages exhibit phenotypes based on surface markers and gene expression. We hypothesized that macrophage polarization state alters gene expression in response to RV infection. Cells were derived from human peripheral blood derived monocytes. M1 and M2 polarization was carried out by using IFN-γ and IL-4, respectively, and RNA was extracted for Affymetrix Human Gene ST2.1 exon arrays. Selected genes were validated by quantitative (q)PCR. Treatment of nonactivated (M0) macrophages with IFN-γ and IL-4 induced the expression of 252 and 153 distinct genes, respectively, including previously-identified M1 and M2 markers. RV infection of M0 macrophages induced upregulation of 232 genes; pathway analysis showed significant overrepresentation of genes involved in IFN-α/β signaling and cytokine signaling in the immune system. RV infection induced differential expression of 195 distinct genes in M1-like macrophages but only seven distinct genes in M2-like-polarized cells. In a secondary analysis, comparison between M0-, RV-infected, and M1-like-polarized, RV-infected macrophages revealed differential expression of 227 genes including those associated with asthma and its exacerbation. qPCR demonstrated increased expression of CCL8, CXCL10, TNFSF10, TNFSF18, IL6, NOD2, and GSDMD and reduced expression of VNN1, AGO1, and AGO2. Together, these data show that, in contrast to M2-like-polarized macrophages, gene expression of M1-like macrophages is highly regulated by RV.

  17. [EVALUATION OF THE HUMAN SENSITIVITY TO SMALLPOX VIRUS BY THE PRIMARY CULTURES OF THE MONOCYTE-MACROPHAGES].

    Science.gov (United States)

    Zamedyanskaya, A S; Titova, K A; Sergeev, Al A; Kabanov, A S; Bulychev, L E; Sergeev, Ar A; Galakhova, D O; Nesterov, A E; Nosareva, O V; Shishkina, L N; Taranov, O S; Omigov, V V; Agafonov, A P; Sergeev, A N

    2016-01-01

    Studies of the primary cultures of granulocytes, mononuclear, and monocyte-macrophage cells derived from human blood were performed using variola virus (VARV) in the doses of 0.001-0.021 PFU/cell (plaques-forming units per cell). Positive dynamics of the virus accumulation was observed only in the monocyte-macrophages with maximum values of virus concentration (5.0-5.5 Ig PFU/ml) mainly within six days after the infection. The fact of VARV replication in the monocyte-macrophages was confirmed by the data of electron microscopy. At the same time, virus vaccines when tested in doses 3.3 and 4.2 Ig PFU/ml did not show the ability to reproduce in these human cells. The people sensitivity to VARV as assessed from the data obtained on human monocyte-macrophages corresponded to -1 PFU (taking into account the smooth interaction of the virus in the body to the cells of this type), which is consistent to previously found theoretical data on the virus sensitivity. The human susceptibility to VARV assessed experimentally can be used to predict the adequacy of developed smallpox models (in vivo) based on susceptible animals. This is necessary for reliable assessment of the efficiency of development of drugs for treatment and prophylaxis of the smallpox.

  18. Contribution of macrophages in the contrast loss in iron oxide-based MRI cancer cell tracking studies

    Science.gov (United States)

    Danhier, Pierre; Deumer, Gladys; Joudiou, Nicolas; Bouzin, Caroline; Levêque, Philippe; Haufroid, Vincent; Jordan, Bénédicte F.; Feron, Olivier; Sonveaux, Pierre; Gallez, Bernard

    2017-01-01

    Magnetic resonance imaging (MRI) cell tracking of cancer cells labeled with superparamagnetic iron oxides (SPIO) allows visualizing metastatic cells in preclinical models. However, previous works showed that the signal void induced by SPIO on T2(*)-weighted images decreased over time. Here, we aim at characterizing the fate of iron oxide nanoparticles used in cell tracking studies and the role of macrophages in SPIO metabolism. In vivo MRI cell tracking of SPIO positive 4T1 breast cancer cells revealed a quick loss of T2* contrast after injection. We next took advantage of electron paramagnetic resonance (EPR) spectroscopy and inductively coupled plasma mass spectroscopy (ICP-MS) for characterizing the evolution of superparamagnetic and non-superparamagnetic iron pools in 4T1 breast cancer cells and J774 macrophages after SPIO labeling. These in vitro experiments and histology studies performed on 4T1 tumors highlighted the quick degradation of iron oxides by macrophages in SPIO-based cell tracking experiments. In conclusion, the release of SPIO by dying cancer cells and the subsequent uptake of iron oxides by tumor macrophages are limiting factors in MRI cell tracking experiments that plead for the use of (MR) reporter-gene based imaging methods for the long-term tracking of metastatic cells. PMID:28467814

  19. Targeting Dexamethasone to Macrophages in a Porcine Endotoxemic Model

    DEFF Research Database (Denmark)

    Granfeldt, Asger; Hvas, Christine Lodberg; Graversen, Jonas Heilskov

    2013-01-01

    -8 minutes. CONCLUSION: Targeted delivery of dexamethasone to macrophages using a humanized CD163 antibody as carrier exhibits anti-inflammatory effects comparable with 50 times higher concentrations of free dexamethasone and does not inhibit endogenous cortisol production. This antibody-drug complex showing......OBJECTIVES: Macrophages are important cells in immunity and the main producers of pro-inflammatory cytokines. The main objective was to evaluate if specific delivery of glucocorticoid to the macrophage receptor CD163 is superior to systemic glucocorticoid therapy in dampening the cytokine response...

  20. Rediscovering peritoneal macrophages in a murine endometriosis model.

    Science.gov (United States)

    Yuan, Ming; Li, Dong; An, Min; Li, Qiuju; Zhang, Lu; Wang, Guoyun

    2017-01-01

    What are the features of peritoneal macrophage subgroups and T helper cells in the development of murine endometriosis? During the development of endometriosis in a murine model, large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs) are polarized into M1 and M2 cells, respectively, and the proportions of T helper (Th) 1, Th17 and T regulatory (T reg ) cells are increased. Numerous studies investigating the etiology and pathogenesis of endometriosis have focused on the polarization states of peritoneal macrophages in endometriosis models and patients, but the results are inconclusive. Further studies indicate that peritoneal macrophages are composed of two distinct subsets: LPMs and SPMs, although their roles in endometriosis are unknown. This study involves a prospective and randomized experiment. Fifty C57BL/6 female mice were randomly allocated to five control and five experimental groups (n = 5/group) according to the presence or absence of transplantation. The transplant periods are 0.25, 3, 14, 28 and 42 days. C57BL/6 mice were utilized to establish an endometriosis model by i.p. injection of allogeneic endometrial segments. Dynamic changes of peritoneal macrophage subsets and polarization profiles were evaluated by flow cytometry (FCM). Macrophage morphology and density were assessed by cell counting under a microscope. Dynamic changes of Th1, Th2, Th17 and T reg cells were estimated by FCM. Peritoneal macrophages are composed of two distinct subsets: LPMs and SPMs. The proportion of SPMs increased immediately after peritoneal injection of endometrial tissues, whereas LPMs showed an opposite trend. Peritoneal macrophages differentiated into both M1 and M2 macrophages. The bidirectional polarization of macrophages was caused by the inverse trends of polarization of LPMs and SPMs. Consistently, the proportions of Th1, Th17 and T reg cells were all increased in mice with endometriosis. N/A. In this study, detection was only performed in a

  1. The Role of Macrophage Lipophagy in Reverse Cholesterol Transport

    Directory of Open Access Journals (Sweden)

    Se-Jin Jeong

    2017-03-01

    Full Text Available Macrophage cholesterol efflux is a central step in reverse cholesterol transport, which helps to maintain cholesterol homeostasis and to reduce atherosclerosis. Lipophagy has recently been identified as a new step in cholesterol ester hydrolysis that regulates cholesterol efflux, since it mobilizes cholesterol from lipid droplets of macrophages via autophagy and lysosomes. In this review, we briefly discuss recent advances regarding the mechanisms of the cholesterol efflux pathway in macrophage foam cells, and present lipophagy as a therapeutic target in the treatment of atherosclerosis.

  2. 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

  3. Macrophage Depletion Ameliorates Peripheral Neuropathy in Aging Mice.

    Science.gov (United States)

    Yuan, Xidi; Klein, Dennis; Kerscher, Susanne; West, Brian L; Weis, Joachim; Katona, Istvan; Martini, Rudolf

    2018-05-09

    Aging is known as a major risk factor for the structure and function of the nervous system. There is urgent need to overcome such deleterious effects of age-related neurodegeneration. Here we show that peripheral nerves of 24-month-old aging C57BL/6 mice of either sex show similar pathological alterations as nerves from aging human individuals, whereas 12-month-old adult mice lack such alterations. Specifically, nerve fibers showed demyelination, remyelination and axonal lesion. Moreover, in the aging mice, neuromuscular junctions showed features typical for dying-back neuropathies, as revealed by a decline of presynaptic markers, associated with α-bungarotoxin-positive postsynapses. In line with these observations were reduced muscle strengths. These alterations were accompanied by elevated numbers of endoneurial macrophages, partially comprising the features of phagocytosing macrophages. Comparable profiles of macrophages could be identified in peripheral nerve biopsies of aging persons. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by applying an orally administered CSF-1R specific kinase (c-FMS) inhibitor. The 6-month-lasting treatment started before development of degenerative changes at 18 months and reduced macrophage numbers in mice by ∼70%, without side effects. Strikingly, nerve structure was ameliorated and muscle strength preserved. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may pave the way for treating degeneration in the aging peripheral nervous system by targeting macrophages, leading to reduced weakness, improved mobility, and eventually increased quality of life in the elderly. SIGNIFICANCE STATEMENT Aging is a major risk factor for the structure and function of the nervous system. Here we show that peripheral nerves of 24-month-old aging mice show similar degenerative alterations as nerves from aging

  4. Real-world health outcomes in adults with moderate-to-severe psoriasis in the United States: a population study using electronic health records to examine patient-perceived treatment effectiveness, medication use, and healthcare resource utilization.

    Science.gov (United States)

    Armstrong, April W; Foster, Shonda A; Comer, Brian S; Lin, Chen-Yen; Malatestinic, William; Burge, Russel; Goldblum, Orin

    2018-06-28

    Little is known regarding real-world health outcomes data among US psoriasis patients, but electronic health records (EHR) that collect structured data at point-of-care may provide opportunities to investigate real-world health outcomes among psoriasis patients. Our objective was to investigate patient-perceived treatment effectiveness, patterns of medication use (duration, switching, and/or discontinuation), healthcare resource utilization, and medication costs using real-world data from psoriasis patients. Data for adults (≥18-years) with a dermatology provider-given diagnosis of psoriasis from 9/2014-9/2015 were obtained from dermatology practices using a widely used US dermatology-specific EHR containing over 500,000 psoriasis patients. Disease severity was captured by static physician's global assessment and body surface area. Patient-perceived treatment effectiveness was assessed by a pre-defined question. Treatment switching and duration were documented. Reasons for discontinuations were assessed using pre-defined selections. Healthcare resource utilization was defined by visit frequency and complexity. From 82,621 patients with psoriasis during the study period, patient-perceived treatment effectiveness was investigated in 2200 patients. The proportion of patients reporting "strongly agree" when asked if their treatment was effective was highest for biologics (73%) and those reporting treatment adherence (55%). In 16,000 patients who received oral systemics and 21,087 patients who received biologics, median treatment duration was longer for those who received biologics (160 vs. 113 days, respectively). Treatment switching was less frequent among patients on systemic monotherapies compared to those on combination therapies. The most common reason for discontinuing biologics was loss of efficacy; the most common reason for discontinuing orals was side effects. In 28,754 patients, higher disease severity was associated with increased healthcare resource

  5. Endocytosis via galactose receptors in vivo. Ligand size directs uptake by hepatocytes and/or liver macrophages

    International Nuclear Information System (INIS)

    Schlepper-Schaefer, J.; Huelsmann, D.; Djovkar, A.; Meyer, H.E.; Herbertz, L.; Kolb, H.; Kolb-Bachofen, V.

    1986-01-01

    The intrahepatic binding and uptake of variously sized ligands with terminal galactosyl residues is rat liver was followed. The ligands were administered to prefixed livers in binding studies and in vivo and in situ (serum-free perfused livers) in uptake studies. Gold sols with different particle diameters were prepared: 5 nm (Au 5 ), 17 nm (Au 17 ), 50 nm (Au 50 ) and coated with galactose exposing glycoproteins (asialofetuin (ASF) or lactosylated BSA (LacBSA)). Electron microscopy of mildly prefixed livers perfused with LacBSA-Au 5 in serum-free medium showed ligand binding to liver macrophages, hepatocytes and endothelial cells. Ligands bound to prefixed cell surfaces reflect the initial distribution of receptor activity: pre-aggregated clusters of ligands are found on liver macrophages, single particles statistically distributed on hepatocytes and pre-aggregated clusters of particles restricted to coated pits on endothelial cells. Ligand binding is prevented in the presence of 80 mM N-acetylgalactosamine (GalNAc), while N-acetylglucosamine (GlcNAc) is without effect. Electron microscopy of livers after ligand injection into the tail vein shows that in vivo uptake of electron-dense galactose particles by liver cells is size-dependent. In vivo uptake by liver macrophages is mediated by galactose-specific recognition as shown by inhibition with GalNAc

  6. Human Induced Pluripotent Stem Cell-Derived Macrophages Share Ontogeny with MYB-Independent Tissue-Resident Macrophages

    Directory of Open Access Journals (Sweden)

    Julian Buchrieser

    2017-02-01

    Full Text Available Tissue-resident macrophages, such as microglia, Kupffer cells, and Langerhans cells, derive from Myb-independent yolk sac (YS progenitors generated before the emergence of hematopoietic stem cells (HSCs. Myb-independent YS-derived resident macrophages self-renew locally, independently of circulating monocytes and HSCs. In contrast, adult blood monocytes, as well as infiltrating, gut, and dermal macrophages, derive from Myb-dependent HSCs. These findings are derived from the mouse, using gene knockouts and lineage tracing, but their applicability to human development has not been formally demonstrated. Here, we use human induced pluripotent stem cells (iPSCs as a tool to model human hematopoietic development. By using a CRISPR-Cas9 knockout strategy, we show that human iPSC-derived monocytes/macrophages develop in an MYB-independent, RUNX1-, and SPI1 (PU.1-dependent fashion. This result makes human iPSC-derived macrophages developmentally related to and a good model for MYB-independent tissue-resident macrophages, such as alveolar and kidney macrophages, microglia, Kupffer cells, and Langerhans cells.

  7. Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident Macrophage Differentiation and Function.

    Science.gov (United States)

    Takata, Kazuyuki; Kozaki, Tatsuya; Lee, Christopher Zhe Wei; Thion, Morgane Sonia; Otsuka, Masayuki; Lim, Shawn; Utami, Kagistia Hana; Fidan, Kerem; Park, Dong Shin; Malleret, Benoit; Chakarov, Svetoslav; See, Peter; Low, Donovan; Low, Gillian; Garcia-Miralles, Marta; Zeng, Ruizhu; Zhang, Jinqiu; Goh, Chi Ching; Gul, Ahmet; Hubert, Sandra; Lee, Bernett; Chen, Jinmiao; Low, Ivy; Shadan, Nurhidaya Binte; Lum, Josephine; Wei, Tay Seok; Mok, Esther; Kawanishi, Shohei; Kitamura, Yoshihisa; Larbi, Anis; Poidinger, Michael; Renia, Laurent; Ng, Lai Guan; Wolf, Yochai; Jung, Steffen; Önder, Tamer; Newell, Evan; Huber, Tara; Ashihara, Eishi; Garel, Sonia; Pouladi, Mahmoud A; Ginhoux, Florent

    2017-07-18

    Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues. Co-culturing human or murine iMacs with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMacs differentiated in vivo into microglia after injection into the brain and into functional alveolar macrophages after engraftment in the lung. Finally, iPSCs from a patient with familial Mediterranean fever differentiated into iMacs with pro-inflammatory characteristics, mimicking the disease phenotype. Altogether, iMacs constitute a source of tissue-resident macrophage precursors that can be used for biological, pathophysiological, and therapeutic studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Alternative activation of macrophages and pulmonary fibrosis are modulated by scavenger receptor, macrophage receptor with collagenous structure.

    Science.gov (United States)

    Murthy, Shubha; Larson-Casey, Jennifer L; Ryan, Alan J; He, Chao; Kobzik, Lester; Carter, A Brent

    2015-08-01

    Alternative activation of alveolar macrophages is linked to fibrosis following exposure to asbestos. The scavenger receptor, macrophage receptor with collagenous structure (MARCO), provides innate immune defense against inhaled particles and pathogens; however, a receptor for asbestos has not been identified. We hypothesized that MARCO acts as an initial signaling receptor for asbestos, polarizes macrophages to a profibrotic M2 phenotype, and is required for the development of asbestos-induced fibrosis. Compared with normal subjects, alveolar macrophages isolated from patients with asbestosis express higher amounts of MARCO and have greater profibrotic polarization. Arginase 1 (40-fold) and IL-10 (265-fold) were higher in patients. In vivo, the genetic deletion of MARCO attenuated the profibrotic environment and pulmonary fibrosis in mice exposed to chrysotile. Moreover, alveolar macrophages from MARCO(-/-) mice polarize to an M1 phenotype, whereas wild-type mice have higher Ym1 (>3.0-fold) and nearly 7-fold more active TGF-β1 in bronchoalveolar lavage (BAL) fluid (BALF). Arg(432) and Arg(434) in domain V of MARCO are required for the polarization of macrophages to a profibrotic phenotype as mutation of these residues reduced FIZZ1 expression (17-fold) compared with cells expressing MARCO. These observations demonstrate that a macrophage membrane protein regulates the fibrotic response to lung injury and suggest a novel target for therapeutic intervention. © FASEB.

  9. Water Resources

    International Nuclear Information System (INIS)

    Abira, M.A.

    1997-01-01

    Water is essential for life and ecological sustenance; its availability is essential component of national welfare and productivity.The country's socio-economic activities are largely dependent on the natural endowment of water resources. Kenya's water resources comprises of surface waters (rivers, lakes and wetlands) and ground water. Surface water forms 86% of total water resources while the rest is ground water Geological, topographical and climatic factors influence the natural availability and distribution of water with the rainfall distribution having the major influence. Water resources in Kenya are continuously under threat of depletion and quality degradation owing to rising population, industrialization, changing land use and settlement activities as well as natural changes. However, the anticipated climate change is likely to exacerbate the situation resulting in increased conflict over water use rights in particular, and, natural resource utilisation in general. The impacts of climate change on the water resources would lead to other impacts on environmental and socio-economic systems

  10. M1 Macrophages but Not M2 Macrophages Are Characterized by Upregulation of CRP Expression via Activation of NFκB: a Possible Role for Ox-LDL in Macrophage Polarization.

    Science.gov (United States)

    Kaplan, Marielle; Shur, Anna; Tendler, Yvgeny

    2018-04-23

    Arterial macrophages comprise a heterogeneous population: pro-inflammatory (M1) and anti-inflammatory (M2). Since C-reactive protein (CRP) is produced by macrophages in atherosclerotic lesions, understanding of CRP regulation in macrophages could be crucial to decipher inflammatory patterns in atherogenesis. We aimed to analyze CRP expression in M1/M2 macrophages and to question whether it involves NFκB signaling pathway. Furthermore, we questioned whether oxidative stress affect macrophage phenotype and modulate macrophage CRP expression. M1/M2 macrophage polarization was validated using THP-1 macrophages. CRP mRNA and protein expression were determined using real-time PCR and immunohistochemistry. Involvement of NFκB was determined by nuclear translocation of p50 subunit and the use of NFκB inhibitor. Involvement of oxidative stress in macrophage phenotypes induction was studied using oxidized-LDL (Ox-LDL) and antioxidants. M1 macrophages were characterized by elevated CRP mRNA expression (by 67%), CRP protein levels (by 108%), and upregulation of NFκB activation compared to control, but these features were not shared by M2 macrophages. Macrophages incubation with Ox-LDL led to a moderate M1 phenotype combined with a M2 phenotype, correlated with increased CRP mRNA expression. Antioxidants inhibited by up to 86% IL6 expression but did not significantly affect IL10 secretion. Antioxidants significantly inhibited CRP expression in M1 macrophages, but not in M2 macrophages. Elevated expression of CRP was characteristic of M1 macrophages rather than M2 through NFκB activation. Oxidative stress could be one of the endogenous triggers for macrophage activation to a mixed M1 and M2 phenotype, in association with increased expression of CRP.

  11. Macrophage ABCA2 deletion modulates intracellular cholesterol deposition, affects macrophage apoptosis, and decreases early atherosclerosis in LDL receptor knockout mice.

    Science.gov (United States)

    Calpe-Berdiel, Laura; Zhao, Ying; de Graauw, Marjo; Ye, Dan; van Santbrink, Peter J; Mommaas, A Mieke; Foks, Amanda; Bot, Martine; Meurs, Illiana; Kuiper, Johan; Mack, Jody T; Van Eck, Miranda; Tew, Kenneth D; van Berkel, Theo J C

    2012-08-01

    The ABCA2 transporter shares high structural homology to ABCA1, which is crucial for the removal of excess cholesterol from macrophages and, by extension, in atherosclerosis. It has been suggested that ABCA2 sequesters cholesterol inside the lysosomes, however, little is known of the macrophage-specific role of ABCA2 in regulating lipid homeostasis in vivo and in modulating susceptibility to atherosclerosis. Chimeras with dysfunctional macrophage ABCA2 were generated by transplantation of bone marrow from ABCA2 knockout (KO) mice into irradiated LDL receptor (LDLr) KO mice. Interestingly, lack of ABCA2 in macrophages resulted in a diminished lesion size in the aortic root (-24.5%) and descending thoracic aorta (-36.6%) associated with a 3-fold increase in apoptotic cells, as measured by both caspase 3 and TUNEL. Upon oxidized LDL exposure, macrophages from wildtype (WT) transplanted animals developed filipin-positive droplets in lysosomal-like compartments, corresponding to free cholesterol (FC) accumulation. In contrast, ABCA2-deficient macrophages displayed an abnormal diffuse distribution of FC over peripheral regions. The accumulation of neutral sterols in lipid droplets was increased in ABCA2-deficient macrophages, but primarily in cytoplasmic clusters and not in lysosomes. Importantly, apoptosis of oxLDL loaded macrophages lacking ABCA2 was increased 2.7-fold, probably as a consequence of the broad cellular distribution of FC. Lack of functional ABCA2 generates abnormalities in intracellular lipid distribution/trafficking in macrophages consistent with its lysosomal sequestering role, leading to an increased susceptibility to apoptosis in response to oxidized lipids and reduced atherosclerotic lesion development. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. 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.

  13. Vpx complementation of 'non-macrophage tropic' R5 viruses reveals robust entry of infectious HIV-1 cores into macrophages.

    Science.gov (United States)

    Mlcochova, Petra; Watters, Sarah A; Towers, Greg J; Noursadeghi, Mahdad; Gupta, Ravindra K

    2014-03-21

    It is now known that clinically derived viruses are most commonly R5 tropic with very low infectivity in macrophages. As these viruses utilize CD4 inefficiently, defective entry has been assumed to be the dominant restriction. The implication is that macrophages are not an important reservoir for the majority of circulating viruses. Macrophage infection by clinical transmitted/founder isolates was 10-100 and 30-450 fold less efficient as compared to YU-2 and BaL respectively. Vpx complementation augmented macrophage infection by non-macrophage tropic viruses to the level of infectivity observed for YU-2 in the absence of Vpx. Augmentation was evident even when Vpx was provided 24 hours post-infection. The entry defect was measured as 2.5-5 fold, with a further 3.5-10 fold block at strong stop and subsequent stages of reverse transcription as compared to YU-2. The overall block to infection was critically dependent on the mechanism of entry as demonstrated by rescue of infection after pseudotyping with VSV-G envelope. Reverse transcription in macrophages could not be enhanced using a panel of cytokines or lipopolysaccharide (LPS). Although the predominant block to clinical transmitted/founder viruses is post-entry, infectivity is determined by Env-CD4 interactions and can be rescued with VSV-G pseudotyping. This suggests a functional link between the optimal entry pathway taken by macrophage tropic viruses and downstream events required for reverse transcription. Consistent with a predominantly post-entry block, replication of R5 using viruses can be greatly enhanced by Vpx. We conclude therefore that entry is not the limiting step and that macrophages represent clinically relevant reservoirs for 'non-macrophage tropic' viruses.

  14. MicroRNA 21 Is a Homeostatic Regulator of Macrophage Polarization and Prevents Prostaglandin E2-Mediated M2 Generation

    OpenAIRE

    Wang, Zhuo; Brandt, Stephanie; Medeiros, Alexandra; Wang, Soujuan; Wu, Hao; Dent, Alexander; Serezani, C. Henrique

    2015-01-01

    Macrophages dictate both initiation and resolution of inflammation. During acute inflammation classically activated macrophages (M1) predominate, and during the resolution phase alternative macrophages (M2) are dominant. The molecular mechanisms involved in macrophage polarization are understudied. MicroRNAs are differentially expressed in M1 and M2 macrophages that influence macrophage polarization. We identified a role of miR-21 in macrophage polarization, and found that cross-talk between ...

  15. Low Levels of IGF-1 Contribute to Alveolar Macrophage Dysfunction in Cystic Fibrosis1

    OpenAIRE

    Bessich, Jamie L.; Nymon, Amanda B.; Moulton, Lisa A; Dorman, Dana; Ashare, Alix

    2013-01-01

    Alveolar macrophages are major contributors to lung innate immunity. Although alveolar macrophages from CFTR−/− mice have impaired function, no study has investigated primary alveolar macrophages in adults with cystic fibrosis (CF). CF patients have low levels of insulin-like growth factor 1 (IGF-1), and our prior studies demonstrate a relationship between IGF-1 and macrophage function. We hypothesize that reduced IGF-1 in CF leads to impaired alveolar macrophage function and chronic infectio...

  16. Inhibiting epigenetic enzymes to improve atherogenic macrophage functions

    NARCIS (Netherlands)

    van den Bossche, Jan; Neele, Annette E.; Hoeksema, Marten A.; de Heij, Femke; Boshuizen, Marieke C. S.; van der Velden, Saskia; de Boer, Vincent C.; Reedquist, Kris A.; de Winther, Menno P. J.

    2014-01-01

    Macrophages determine the outcome of atherosclerosis by propagating inflammatory responses, foam cell formation and eventually necrotic core development. Yet, the pathways that regulate their atherogenic functions remain ill-defined. It is now apparent that chromatin remodeling chromatin modifying

  17. HIV-1 Nef in Macrophage-Mediated Disease Pathogenesis

    Science.gov (United States)

    Lamers, Susanna L.; Fogel, Gary B.; Singer, Elyse J.; Salemi, Marco; Nolan, David J.; Huysentruyt, Leanne C.; McGrath, Michael S.

    2013-01-01

    Combined anti-retroviral therapy (cART) has significantly reduced the number of AIDS-associated illnesses and changed the course of HIV-1 disease in developed countries. Despite the ability of cART to maintain high CD4+ T-cell counts, a number of macrophage-mediated diseases can still occur in HIV-infected subjects. These diseases include lymphoma, metabolic diseases, and HIV-associated neurological disorders. Within macrophages, the HIV-1 regulatory protein “Nef” can modulate surface receptors, interact with signaling pathways, and promote specific environments that contribute to each of these pathologies. Moreover, genetic variation in Nef may also guide the macrophage response. Herein, we review findings relating to the Nef–macrophage interaction and how this relationship contributes to disease pathogenesis. PMID:23215766

  18. EVIDENCE FOR THE MACROPHAGE INDUCING GENE IN MYCOBACTERIUM INTRACELLULARE

    Science.gov (United States)

    Background: The Mycobacterium avium Complex (MAC) includes the species M. avium (MA), M. intracellulare (MI), and possibly others. Organisms belonging to the MAC are phylogenetically closely related, opportunistic pathogens. The macrophage inducing gene (mig) is the only well-des...

  19. A stratified myeloid system, the challenge of understanding macrophage diversity.

    Science.gov (United States)

    Geissmann, F; Mass, E

    2015-12-01

    The present issue of 'Seminars in Immunology' addresses the topic of macrophage biology, 100 years after the death of Elie Metchnikoff (May 1845-July 1916). As foreseen by Metchnikoff, the roles of macrophages in the maintenance of homeostasis and immunity against pathogens have become a broad and active area of investigation. We now start to realize that the myeloid system includes a multiplicity of cell types with diverse developmental origins and functions. Therefore, the textbook picture of a plastic and multifunctional macrophage does not meet the requirements of our current knowledge anymore. Further development toward a quantitative and molecular understanding of myeloid cell biology in vivo and their roles in tissue homeostasis and remodeling will benefit from taking this complexity into account. A tentative model to help in this pursuit and account for myeloid cell and macrophage diversity is discussed below. Copyright © 2016. Published by Elsevier Ltd.

  20. Macrophages are necessary for epimorphic regeneration in African spiny mice.

    Science.gov (United States)

    Simkin, Jennifer; Gawriluk, Thomas R; Gensel, John C; Seifert, Ashley W

    2017-05-16

    How the immune system affects tissue regeneration is not well understood. In this study, we used an emerging mammalian model of epimorphic regeneration, the African spiny mouse, to examine cell-based inflammation and tested the hypothesis that macrophages are necessary for regeneration. By directly comparing inflammatory cell activation in a 4 mm ear injury during regeneration ( Acomys cahirinus ) and scarring ( Mus musculus ), we found that both species exhibited an acute inflammatory response, with scarring characterized by stronger myeloperoxidase activity. In contrast, ROS production was stronger and more persistent during regeneration. By depleting macrophages during injury, we demonstrate a functional requirement for these cells to stimulate regeneration. Importantly, the spatial distribution of activated macrophage subtypes was unique during regeneration with pro-inflammatory macrophages failing to infiltrate the regeneration blastema. Together, our results demonstrate an essential role for inflammatory cells to regulate a regenerative response.

  1. Macrophage migration inhibitory factor and autism spectrum disorders

    NARCIS (Netherlands)

    Grigorenko, Elena L.; Han, Summer S.; Yrigollen, Carolyn M.; Leng, Lin; Mizue, Yuka; Anderson, George M.; Mulder, Erik J.; de Bildt, Annelies; Minderaa, Ruud B.; Volkmar, Fred R.; Chang, Joseph T.; Bucala, Richard

    OBJECTIVE. Autistic spectrum disorders are childhood neurodevelopmental disorders characterized by social and communicative impairment and repetitive and stereotypical behavior. Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity that promotes

  2. Macrophage migration inhibitory factor is elevated in obese adolescents

    NARCIS (Netherlands)

    Kamchybekov, Uran; Figulla, Hans R.; Gerdes, Norbert; Jung, Christian

    2012-01-01

    Objectives: The prevalence of obesity in childhood and adolescence is continuing rising. Macrophage migration inhibitory factor (MIF) participates in inflammatory and immune responses as a pro-inflammatory cytokine. The present study aimed to investigate MIF in overweight adolescents. Methods:

  3. HIV aspartyl peptidase inhibitors interfere with cellular proliferation, ultrastructure and macrophage infection of Leishmania amazonensis.

    Directory of Open Access Journals (Sweden)

    Lívia O Santos

    Full Text Available BACKGROUND: Leishmania is the etiologic agent of leishmanisais, a protozoan disease whose pathogenic events are not well understood. Current therapy is suboptimal due to toxicity of the available therapeutic agents and the emergence of drug resistance. Compounding these problems is the increase in the number of cases of Leishmania-HIV coinfection, due to the overlap between the AIDS epidemic and leishmaniasis. METHODOLOGY/PRINCIPAL FINDINGS: In the present report, we have investigated the effect of HIV aspartyl peptidase inhibitors (PIs on the Leishmania amazonensis proliferation, ultrastructure, interaction with macrophage cells and expression of classical peptidases which are directly involved in the Leishmania pathogenesis. All the HIV PIs impaired parasite growth in a dose-dependent fashion, especially nelfinavir and lopinavir. HIV PIs treatment caused profound changes in the leishmania ultrastructure as shown by transmission electron microscopy, including cytoplasm shrinking, increase in the number of lipid inclusions and some cells presenting the nucleus closely wrapped by endoplasmic reticulum resembling an autophagic process, as well as chromatin condensation which is suggestive of apoptotic death. The hydrolysis of HIV peptidase substrate by L. amazonensis extract was inhibited by pepstatin and HIV PIs, suggesting that an aspartyl peptidase may be the intracellular target of the inhibitors. The treatment with HIV PIs of either the promastigote forms preceding the interaction with macrophage cells or the amastigote forms inside macrophages drastically reduced the association indexes. Despite all these beneficial effects, the HIV PIs induced an increase in the expression of cysteine peptidase b (cpb and the metallopeptidase gp63, two well-known virulence factors expressed by Leishmania spp. CONCLUSIONS/SIGNIFICANCE: In the face of leishmaniasis/HIV overlap, it is critical to further comprehend the sophisticated interplays among Leishmania

  4. Role of macrophages in the immune response to hepatocytes

    International Nuclear Information System (INIS)

    Bumgardner, G.L.; Chen, S.; Almond, S.P.; Ascher, N.L.; Payne, W.D.; Matas, A.J.

    1990-01-01

    The purpose of this study was to determine the role of host macrophages in the development of allospecific cytolytic T cells (allo-CTLs) in response to purified allogeneic MHC Class I+, Class II- hepatocytes in vivo in hepatocyte sponge matrix allografts (HC-SMA). Depletion of antigen-presenting cells (APCs) from responder splenocytes in mixed lymphocyte hepatocyte culture (MLHC) inhibits the development of allo-CTLs in response to purified hepatocytes. First the ability of sponge macrophages to function as accessory cells in indirect presentation of hepatocyte Class I antigen was tested in MLHC. We found that addition of irradiated sponge cells (a source of sponge macrophages) restored the development of allo-CTLs in MLHC depleted of responder APCs. Therefore, radioresistant sponge macrophages can function as accessory cells in MLHC. We next employed silica as an immunotherapy targeted against host macrophages and assessed the effect on development of allo-CTLs in HC-SMA. We found that local (intrasponge) silica treatment completely inhibited the development of allo-CTLs in HC-SMA. Combined local and systemic silica treatment resulted in inhibition of allocytotoxicity comparable to local silica treatment alone in the doses tested. We conclude that host macrophages which infiltrate HC-SMA can function as accessory cells in vitro in MLHC and that both infiltrating host macrophages and lymphocytes participate in the development of an alloimmune response to purified hepatocytes in vivo. This interaction may involve indirect antigen presentation of hepatocyte Class I antigen by macrophages to host lymphocytes which accumulate in HC-SMA

  5. Role of Alveolar Macrophages in Chronic Obstructive Pulmonary Disease

    OpenAIRE

    Vlahos, Ross; Bozinovski, Steven

    2014-01-01

    Alveolar macrophages (AMs) represent a unique leukocyte population that responds to airborne irritants and microbes. This distinct microenvironment coordinates the maturation of long-lived AMs, which originate from fetal blood monocytes and self-renew through mechanisms dependent on GM-CSF and CSF-1 signaling. Peripheral blood monocytes can also replenish lung macrophages; however, this appears to occur in a stimuli specific manner. In addition to mounting an appropriate immune response durin...

  6. Clinical features in patients with long-lasting macrophagic myofasciitis

    OpenAIRE

    Muriel eRIGOLET; Jessie eAOUIZERATE; Jessie eAOUIZERATE; Maryline eCOUETTE; Nilusha eTHANGARAJAH; Nilusha eTHANGARAJAH; Mehdi eAOUN-SEBAITI; Romain Kroum GHERARDI; Romain Kroum GHERARDI; Romain Kroum GHERARDI; Josette eCADUSSEAU; Josette eCADUSSEAU; Francois Jerome eAUTHIER; Francois Jerome eAUTHIER; Francois Jerome eAUTHIER

    2014-01-01

    Macrophagic myofasciitis (MMF) is an emerging condition characterized by specific muscle lesions assessing abnormal long-term persistence of aluminium hydroxide within macrophages at the site of previous immunization. Affected patients usually are middle-aged adults, mainly presenting with diffuse arthromyalgias, chronic fatigue, and marked cognitive deficits, not related to pain, fatigue or depression. Clinical features usually correspond to that observed in chronic fatigue syndrome/myalgic ...

  7. Clinical Features in Patients with Long-Lasting Macrophagic Myofasciitis

    OpenAIRE

    Rigolet, Muriel; Aouizerate, Jessie; Couette, Maryline; Ragunathan-Thangarajah, Nilusha; Aoun-Sebaiti, Mehdi; Gherardi, Romain Kroum; Cadusseau, Josette; Authier, François Jérôme

    2014-01-01

    Macrophagic myofasciitis (MMF) is an emerging condition characterized by specific muscle lesions assessing abnormal long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization. Affected patients usually are middle-aged adults, mainly presenting with diffuse arthromyalgias, chronic fatigue, and marked cognitive deficits, not related to pain, fatigue, or depression. Clinical features usually correspond to that observed in chronic fatigue syndrome/myalgic ...

  8. In Vitro Toxicity of Aluminum Nanoparticles in Rat Alveolar Macrophages

    Science.gov (United States)

    2006-03-01

    including intravenous, intramuscular , and subcutaneous injections, and including oral and ocular administration (Kreuter, 1991). NPs allow delivery of... NANOPARTICLES IN RAT ALVEOLAR MACROPHAGES THESIS Andrew J Wagner, 1st Lt, USAF AFIT/GES/ENV/06M-06 DEPARTMENT OF THE AIR FORCE AIR UNIVERSITY ORCE...TOXICITY OF ALUMINUM NANOPARTICLES IN RAT ALVEOLAR MACROPHAGES THESIS Presented to the Faculty Department of Systems and Engineering

  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. The role of HFE genotype in macrophage phenotype.

    Science.gov (United States)

    Nixon, Anne M; Neely, Elizabeth; Simpson, Ian A; Connor, James R

    2018-02-01

    Iron regulation is essential for cellular energy production. Loss of cellular iron homeostasis has critical implications for both normal function and disease progression. The H63D variant of the HFE gene is the most common gene variant in Caucasians. The resulting mutant protein alters cellular iron homeostasis and is associated with a number of neurological diseases and cancer. In the brain, microglial and infiltrating macrophages are critical to maintaining iron homeostasis and modulating inflammation associated with the pathogenic process in multiple diseases. This study addresses whether HFE genotype affects macrophage function and the implications of these findings for disease processes. Bone marrow macrophages were isolated from wildtype and H67D HFE knock-in mice. The H67D gene variant in mice is the human equivalent of the H63D variant. Upon differentiation, the macrophages were used to analyze iron regulatory proteins, cellular iron release, migration, phagocytosis, and cytokine expression. The results of this study demonstrate that the H67D HFE genotype significantly impacts a number of critical macrophage functions. Specifically, fundamental activities such as proliferation in response to iron exposure, L-ferritin expression in response to iron loading, secretion of BMP6 and cytokines, and migration and phagocytic activity were all found to be impacted by genotype. Furthermore, we demonstrated that exposure to apo-Tf (iron-poor transferrin) can increase the release of iron from macrophages. In normal conditions, 70% of circulating transferrin is unsaturated. Therefore, the ability of apo-Tf to induce iron release could be a major regulatory mechanism for iron release from macrophages. These studies demonstrate that the HFE genotype impacts fundamental components of macrophage phenotype that could alter their role in degenerative and reparative processes in neurodegenerative disorders.

  11. Macrophages and depression - a misalliance or well-arranged marriage?

    Science.gov (United States)

    Roman, Adam; Kreiner, Grzegorz; Nalepa, Irena

    2013-01-01

    Depression is a severe medical condition with multiple manifestations and diverse, largely unknown etiologies. The immune system, particularly macrophages, plays an important role in the pathology of the illness. Macrophages represent a heterogeneous population of immune cells that is dispersed throughout the body. The central nervous system is populated by several types of macrophages, including microglia, perivascular cells, meningeal and choroid plexus macrophages and pericytes. These cells occupy different brain compartments and have various functions. Under basal conditions, brain macrophages support the proper function of neural cells, organize and preserve the neuronal network and maintain homeostasis. As cells of the innate immune system, they recognize and react to any disturbances in homeostasis, eliminating pathogens or damaged cells, terminating inflammation and proceeding to initiate tissue reconstruction. Disturbances in these processes result in diverse pathologies. In particular, tissue stress or malfunction, both in the brain and in the periphery, produce sustained inflammatory states, which may cause depression. Excessive release of proinflammatory mediators is responsible for alterations of neurotransmitter systems and the occurrence of depressive symptoms. Almost all antidepressive drugs target monoamine or serotonin neurotransmission and also have anti-inflammatory or immunosuppressive properties. In addition, non-pharmacological treatments, such as electroconvulsive shock, can also exert anti-inflammatory effects. Recent studies have shown that antidepressive therapies can affect the functional properties of peripheral and brain macrophages and skew them toward the anti-inflammatory M2 phenotype. Because macrophages can affect outcome of inflammatory diseases, alleviate sickness behavior and improve cognitive function, it is possible that the effects of antidepressive treatments may be, at least in part, mediated by changes in macrophage

  12. Modulation of macrophage antimicrobial mechanisms by pathogenic mycobacteria

    OpenAIRE

    Mueller, P.; Pieters, J.

    2006-01-01

    Tuberculosis remained a mysterious disease until Koch was able to demonstrate in the late 1800s that it was caused by a bacterium spread by aerosols, Mycobacterium tuberculosis. Today, tuberculosis still is a major health problem causing approximately 2 million deaths annually with about one third of the world's population being latently infected with M. tuberculosis. The secret of success for M. tuberculosis lies in its ability to persist inside host cells, the macrophages. Whereas macrophag...

  13. 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.

  14. Inflammation and wound healing: The role of the macrophage

    Science.gov (United States)

    Koh, Timothy J.; DiPietro, Luisa Ann

    2013-01-01

    The macrophage is a prominent inflammatory cell in wounds, but its role in healing remains incompletely understood. Macrophages have been described to have many functions in wounds, including host defense, the promotion and resolution of inflammation, the removal of apoptotic cells, and the support of cell proliferation and tissue restoration following injury. Recent studies suggest that macrophages exist in several different phenotypic states within the healing wound, and that the influence of these cells on each stage of repair varies with the specific phenotypes. While the macrophage is beneficial to the repair of normally healing wounds, this pleotropic cell type may promote excessive inflammation and/or fibrosis in certain circumstances. Emerging evidence suggests that macrophage dysfunction is a component of the pathogenesis of non-healing and poorly healing wounds. Due to advances in the understanding of this multi-functional cell, the macrophage continues to be an attractive therapeutic target both to reduce fibrosis and scarring, and to improve healing of chronic wounds. PMID:21740602

  15. Liver macrophages: friend or foe during hepatitis B infection?

    Science.gov (United States)

    Faure-Dupuy, Suzanne; Durantel, David; Lucifora, Julie

    2018-05-17

    The Hepatitis B virus chronically infects the liver of 250 million people worldwide. Over the past decades, major advances have been made in the understanding of Hepatitis B virus life cycle in hepatocytes. Beside these parenchymal cells, the liver also contains resident and infiltrating myeloid cells involved in immune responses to pathogens and much less is known about their interplay with Hepatitis B virus. In this review, we summarized and discussed the current knowledge of the role of liver macrophages (including Kupffer cells and liver monocyte-derived macrophages), in HBV infection. While it is still unclear if liver macrophages play a role in the establishment and persistence of HBV infection, several studies disclosed data suggesting that HBV would favour liver macrophage anti-inflammatory phenotypes and thereby increase liver tolerance. In addition, alternatively activated liver macrophages might also play in the long term a key role in hepatitis B associated pathogenesis, especially through the activation of hepatic stellate cells. Therapies aiming at a transient activation of pro-inflammatory liver macrophages should therefore be considered for the treatment of chronic HBV infection. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Dysregulated Functions of Lung Macrophage Populations in COPD.

    Science.gov (United States)

    Kapellos, Theodore S; Bassler, Kevin; Aschenbrenner, Anna C; Fujii, Wataru; Schultze, Joachim L

    2018-01-01

    Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema. Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses. To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire. In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations. We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD. In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD.

  17. Macrophages are required to coordinate mouse digit tip regeneration.

    Science.gov (United States)

    Simkin, Jennifer; Sammarco, Mimi C; Marrero, Luis; Dawson, Lindsay A; Yan, Mingquan; Tucker, Catherine; Cammack, Alex; Muneoka, Ken

    2017-11-01

    In mammals, macrophages are known to play a major role in tissue regeneration. They contribute to inflammation, histolysis, re-epithelialization, revascularization and cell proliferation. Macrophages have been shown to be essential for regeneration in salamanders and fish, but their role has not been elucidated in mammalian epimorphic regeneration. Here, using the regenerating mouse digit tip as a mammalian model, we demonstrate that macrophages are essential for the regeneration process. Using cell-depletion strategies, we show that regeneration is completely inhibited; bone histolysis does not occur, wound re-epithelialization is inhibited and the blastema does not form. Although rescue of epidermal wound closure in the absence of macrophages promotes blastema accumulation, it does not rescue cell differentiation, indicating that macrophages play a key role in the redifferentiation of the blastema. We provide additional evidence that although bone degradation is a component, it is not essential to the overall regenerative process. These findings show that macrophages play an essential role in coordinating the epimorphic regenerative response in mammals. © 2017. Published by The Company of Biologists Ltd.

  18. Dysregulated Functions of Lung Macrophage Populations in COPD

    Science.gov (United States)

    Bassler, Kevin; Aschenbrenner, Anna C.

    2018-01-01

    Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema. Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses. To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire. In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations. We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD. In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD. PMID:29670919

  19. Human macrophage hemoglobin-iron metabolism in vitro

    International Nuclear Information System (INIS)

    Custer, G.; Balcerzak, S.; Rinehart, J.

    1982-01-01

    An entirely in vitro technique was employed to characterize hemoglobin-iron metabolism by human macrophages obtained by culture of blood monocytes and pulmonary alveolar macrophages. Macrophages phagocytized about three times as many erythrocytes as monocytes and six times as many erythrocytes as pulmonary alveolar macrophages. The rate of subsequent release of 59 Fe to the extracellular transferrin pool was two- to fourfold greater for macrophages as compared to the other two cell types. The kinetics of 59 Fe-transferrin release were characterized by a relatively rapid early phase (hours 1-4) followed by a slow phase (hours 4-72) for all three cell types. Intracellular movement of iron was characterized by a rapid shift from hemoglobin to ferritin that was complete with the onset of the slow phase of extracellular release. A transient increase in 59 Fe associated with an intracellular protein eluting with transferrin was also observed within 1 hour after phagocytosis. The process of hemoglobin-iron release to extracellular transferrin was inhibited at 4 degrees C but was unaffected by inhibitory of protein synthesis, glycolysis, microtubule function, and microfilament function. These data emphasize the rapidity of macrophage hemoglobin iron metabolism, provide a model for characterization of this process in vitro, and in general confirm data obtained utilizing in vivo animal models

  20. USPIO-labeling in M1 and M2-polarized macrophages: An in vitro study using a clinical magnetic resonance scanner.

    Science.gov (United States)

    Zini, Chiara; Venneri, Mary A; Miglietta, Selenia; Caruso, Damiano; Porta, Natale; Isidori, Andrea M; Fiore, Daniela; Gianfrilli, Daniele; Petrozza, Vincenzo; Laghi, Andrea

    2018-08-01

    Aim of the study was to evaluate USPIO labeling in different macrophage populations using a clinical 3.0T MR unit with optical and electron microscopy as the gold standard. Human monocytic cell line THP-1 cells were differentiated into macrophages. Afterwards, M0 macrophages were incubated with IL-4 and IL-13 in order to obtain M2 polarized macrophages or with IFN-gamma and LPS for classical macrophage activation (M1). These groups were incubated with USPIO-MR contrast agent (P904) for 36 hr; M0, M0 + P904, M1 +  P904, and M2 + P904 were analyzed in gel phantoms with a 3.0T MR scanner. m-RNA of M1 and M2 markers confirmed the polarization of THP-1-derived macrophages. M2 + P904 showed a much higher T1 signal (p <  0.0001), a significantly lower (p < 0.0001) T2* signal, and significantly higher R* (p < 0.0001) compared to the other populations. Hystological analysis confirmed higher iron content in the M2-polarized population compared to both M1-polarized (p = 0.04) and M0-P904 (p = 0.003). Ultrastructure analysis demonstrated ubiquitous localization of P904 within the cellular compartments. Our results demonstrate that a selective USPIO-labeling of different macrophage populations can be detected in vitro using the 3.0T clinical scanner. © 2017 Wiley Periodicals, Inc.

  1. One small step for a yeast--microevolution within macrophages renders Candida glabrata hypervirulent due to a single point mutation.

    Directory of Open Access Journals (Sweden)

    Sascha Brunke

    2014-10-01

    Full Text Available Candida glabrata is one of the most common causes of candidemia, a life-threatening, systemic fungal infection, and is surpassed in frequency only by Candida albicans. Major factors contributing to the success of this opportunistic pathogen include its ability to readily acquire resistance to antifungals and to colonize and adapt to many different niches in the human body. Here we addressed the flexibility and adaptability of C. glabrata during interaction with macrophages with a serial passage approach. Continuous co-incubation of C. glabrata with a murine macrophage cell line for over six months resulted in a striking alteration in fungal morphology: The growth form changed from typical spherical yeasts to pseudohyphae-like structures - a phenotype which was stable over several generations without any selective pressure. Transmission electron microscopy and FACS analyses showed that the filamentous-like morphology was accompanied by changes in cell wall architecture. This altered growth form permitted faster escape from macrophages and increased damage of macrophages. In addition, the evolved strain (Evo showed transiently increased virulence in a systemic mouse infection model, which correlated with increased organ-specific fungal burden and inflammatory response (TNFα and IL-6 in the brain. Similarly, the Evo mutant significantly increased TNFα production in the brain on day 2, which is mirrored in macrophages confronted with the Evo mutant, but not with the parental wild type. Whole genome sequencing of the Evo strain, genetic analyses, targeted gene disruption and a reverse microevolution experiment revealed a single nucleotide exchange in the chitin synthase-encoding CHS2 gene as the sole basis for this phenotypic alteration. A targeted CHS2 mutant with the same SNP showed similar phenotypes as the Evo strain under all experimental conditions tested. These results indicate that microevolutionary processes in host-simulative conditions

  2. Electronics and electronic systems

    CERN Document Server

    Olsen, George H

    1987-01-01

    Electronics and Electronic Systems explores the significant developments in the field of electronics and electronic devices. This book is organized into three parts encompassing 11 chapters that discuss the fundamental circuit theory and the principles of analog and digital electronics. This book deals first with the passive components of electronic systems, such as resistors, capacitors, and inductors. These topics are followed by a discussion on the analysis of electronic circuits, which involves three ways, namely, the actual circuit, graphical techniques, and rule of thumb. The remaining p

  3. Normal macrophage function in copper deficient mice

    International Nuclear Information System (INIS)

    Lukasewycz, O.A.; Kolquist, K.L.; Prohaska, J.R.

    1986-01-01

    Copper deficiency (-Cu) was produced in C57 BL and C58 mice by feeding a low copper diet (modified AIN-76A) from birth. Mice given supplemental copper in the drinking water (+Cu) served as controls. Copper status was monitored by assay of ceruloplasmin (CP) activity. Macrophages (M0) were obtained from matched +Cu and -Cu male 7 week-old mice by peritoneal lavage 3 days after thioglycollate stimulation. M0 were assayed in terms of lipopolysaccharide-induced hexose monophosphate shunt activity by monitoring 14 CO 2 production from [1- 14 C]-glucose and by the determination of phagocytic index using fluorescein labelled latex bead ingestion. M0 from -Cu mice were equivalent to those of +Cu mice in both these parameters. However, superoxide dismutase and cytochrome oxidase activities were both significantly lower in -Cu M0, confirming a functional copper deficiency. Previous results from this laboratory have shown that -Cu mice have a decreased antibody response to sheep erythrocyte antigens and a diminished reactivity to B and T cell mitogens. These immunological insufficiencies appear to be proportional to the severity of copper depletion as determined by CP levels. Furthermore, -Cu lymphocytes exhibit depressed mixed lymphocyte reactivity consistent with alterations at the membrane surface. The present results suggest that M0/monocytes are less severely affected than lymphocytes in copper deficiency states

  4. [Macrophage colony stimulating factor enhances non-small cell lung cancer invasion and metastasis by promoting macrophage M2 polarization].

    Science.gov (United States)

    Li, Y J; Yang, L; Wang, L P; Zhang, Y

    2017-06-23

    Objective: To investigate the key cytokine which polarizes M2 macrophages and promotes invasion and metastasis in non-small cell lung cancer (NSCLC). Methods: After co-culture with A549 cells in vitro, the proportion of CD14(+) CD163(+) M2 macrophages in monocytes and macrophage colony stimulating factor (M-CSF) levels in culture supernatant were detected by flow cytometry, ELISA assay and real-time qPCR, respectively. The effects of CD14(+) CD163(+) M2 macrophages on invasion of A549 cells and angiogenesis of HUVEC cells were measured by transwell assay and tubule formation assay, respectively. The clinical and prognostic significance of M-CSF expression in NSCLC was further analyzed. Results: The percentage of CD14(+) CD163(+) M2 macrophages in monocytes and the concentration of M-CSF in the supernatant followed by co-culture was (12.03±0.46)% and (299.80±73.76)pg/ml, respectively, which were significantly higher than those in control group [(2.80±1.04)% and (43.07±11.22)pg/ml, respectively, P macrophages in vitro . M2 macrophages enhanced the invasion of A549 cells (66 cells/field vs. 26 cells/field) and the angiogenesis of HUVEC cells (22 tubes/field vs. 8 tubes/field). The mRNA expression of M-CSF in stage Ⅰ-Ⅱ patients (16.23±4.83) was significantly lower than that in stage Ⅲ-Ⅳ (53.84±16.08; P macrophages, which can further promote the metastasis and angiogenesis of NSCLC. M-CSF could be used as a potential therapeutic target of NSCLC.

  5. Mitogen-activated protein kinase phosphatase-1 expression in macrophages is controlled by lymphocytes during macrophage activation.

    Science.gov (United States)

    Luo, Chong; Yang, Xiqiang; Yao, Lan; Jiang, Liping; Liu, Wei; Li, Xin; Wang, Lijia

    2012-01-01

    The viewpoints on the control of innate immune cells by the adaptive immune system during sepsis remain controversial. Mitogen-activated protein kinase phosphatase-1 (MKP-1) is essential to the negative control of innate immunity and suppresses the activation of macrophages by inhibiting activated mitogen-activated protein kinase (MAPK). The purpose of the current study was to observe inflammatory response and macrophage activation in mice with severe combined immunodeficiency (SCID) with endotoxemia and to determine the role of MKP-1 in the control of macrophage activation by the adaptive immune system. Endotoxemia was induced in wild-type and SCID mice by an intraperitoneal injection of lipopolysaccharide (LPS), and all of the SCID mice died. SCID mice produced more inflammatory cytokines than BALB/c mice systemically and locally. TNF-α mRNA expression was higher and MKP-1 mRNA expression was lower in peritoneal macrophages (PMa) from SCID mice compared to PMa from wild-type mice after and even before LPS injection. Thioglycollate-stimulated PMa from wild-type mice were stimulated with LPS in vitro in the presence or absence of pan-T cells. The levels of TNF-α and IL-6 were higher in the supernatants from PMa cultured alone compared to PMa co-cultured with pan-T cells, and PMa MKP-1 mRNA and protein expression were higher when PMa were co-cultured with pan-T cells. Therefore, pan-T cells can up-regulate MKP-1 expression in macrophages and inhibit the secretion of inflammatory cytokines secretion by macrophages. In SCID mice, lymphocyte deficiency, especially T cell deficiency, causes insufficient MKP-1 expression in macrophages, which can be responsible for the severe inflammation and bad prognosis of septic SCID mice. MKP-1 plays an important role in the control of macrophage activation by the adaptive immune system.

  6. Degradation of connective tissue matrices by macrophages. III. Morphological and biochemical studies on extracellular, pericellular, and intracellular events in matrix proteolysis by macrophages in culture

    International Nuclear Information System (INIS)

    Werb, Z.; Bainton, D.F.; Jones, P.A.

    1980-01-01

    The aim of the present study was to determine the localization of macrophage-mediated degradation of matrix proteins. The sites of matrix degradation were examined ultrastructurally, and the effects of modulation of macrophage secretion, endocytosis, and activity of macrophage hydrolases on matrix degradation were monitored biochemically

  7. C-reactive protein interaction with macrophages: in vitro induction of tumor cytotoxicity, and characterization of C-reactive protein binding to macrophages

    International Nuclear Information System (INIS)

    Zahedi, K.A.

    1987-01-01

    The ability of C-reactive protein (CRP) to activate macrophages to tumoricidal state was examined. CRP was able to activate macrophages to kill tumor cells. The activation was shown to be due to CRP and not to low levels of other activators present in the CRP preparations, since specific removal of CRP led to abrogation of the CRP mediated activation of macrophages. The role of lipopolysaccharide (LPS) as a contaminating activator was eliminated by showing the ability of CRP preparations to activate macrophages from LPS non-responsive strains of mice, and to activate macrophages under conditions which specifically inactivated or removed the contaminating LPS. In order to exclude the possibility of indirect activation of macrophages by other cells present in the peritoneal exudate cell population, effect of CRP on pure macrophages was examined. Bone marrow derived macrophages as well as well as macrophage cell lines exhibited a significant increase in their capacity to kill tumor cells after treatment with CRP. The nature of CRP and macrophage interaction was examined using radioiodinated CRP. Labelled CRP bound specifically to macrophages and macrophage cell lines

  8. Uranium resources

    International Nuclear Information System (INIS)

    Gangloff, A.

    1978-01-01

    It is first indicated how to evaluate the mining resources as a function of the cost of production and the degree of certainty in the knowledge of the deposit. A table is given of the world resources (at the beginning 1977) and resources and reserves are compared. There is a concordance between requirements and possible production until 1990. The case of France is examined: known reserves, present and future prospection, present production (In 1978 2200 T of U metal will be produced from 3 French processing plants), production coming from Cogema. A total production of 2000 T in 1980 and 10.000 in 1985 is expected [fr

  9. Tumor-associated macrophages as a paradigm of macrophage plasticity, diversity, and polarization: lessons and open questions.

    Science.gov (United States)

    Mantovani, Alberto; Locati, Massimo

    2013-07-01

    Macrophages are present in all body compartments, including cancerous tissues, and their functions are profoundly affected by signals from the microenvironment under homeostatic and pathological conditions. Tumor-associated macrophages are a major cellular component of cancer-related inflammation and have served as a paradigm for the plasticity and functional polarization of mononuclear phagocytes. Tumor-associated macrophages can exert dual influence of cancer depending on the activation state, with classically activated (M1) and alternatively activated (M2) cells generally exerting antitumoral and protumoral functions, respectively. These are extremes in a continuum of polarization states in a universe of diversity. Tumor-associated macrophages affect virtually all aspects of tumor tissues, including stem cells, metabolism, angiogenesis, invasion, and metastasis. Progress has been made in defining signaling molecules, transcription factors, epigenetic changes, and repertoire of microRNAs underlying macrophage polarization. Preclinical and early clinical data suggest that macrophages may serve as tools for the development of innovative diagnostic and therapeutic strategies in cancer and chronic nonresolving inflammatory diseases.

  10. 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

  11. Networked T cell death following macrophage infection by Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Stephen H-F Macdonald

    Full Text Available BACKGROUND: Depletion of T cells following infection by Mycobacterium tuberculosis (Mtb impairs disease resolution, and interferes with clinical test performance that relies on cell-mediated immunity. A number of mechanisms contribute to this T cell suppression, such as activation-induced death and trafficking of T cells out of the peripheral circulation and into the diseased lungs. The extent to which Mtb infection of human macrophages affects T cell viability however, is not well characterised. METHODOLOGY/PRINCIPAL FINDINGS: We found that lymphopenia (<1.5 × 10(9 cells/l was prevalent among culture-positive tuberculosis patients, and lymphocyte counts significantly improved post-therapy. We previously reported that Mtb-infected human macrophages resulted in death of infected and uninfected bystander macrophages. In the current study, we sought to examine the influence of infected human alveolar macrophages on T cells. We infected primary human alveolar macrophages (the primary host cell for Mtb or PMA-differentiated THP-1 cells with Mtb H37Ra, then prepared cell-free supernatants. The supernatants of Mtb-infected macrophages caused dose-dependent, caspase-dependent, T cell apoptosis. This toxic effect of infected macrophage secreted factors did not require TNF-α or Fas. The supernatant cytotoxic signal(s were heat-labile and greater than 50 kDa in molecular size. Although ESAT-6 was toxic to T cells, other Mtb-secreted factors tested did not influence T cell viability; nor did macrophage-free Mtb bacilli or broth from Mtb cultures. Furthermore, supernatants from Mycobacterium bovis Bacille de Calmette et Guerin (BCG- infected macrophages also elicited T cell death suggesting that ESAT-6 itself, although cytotoxic, was not the principal mediator of T cell death in our system. CONCLUSIONS: Mtb-Infected macrophages secrete heat-labile factors that are toxic to T cells, and may contribute to the immunosuppression seen in tuberculosis as well as

  12. Seaweed resources

    Digital Repository Service at National Institute of Oceanography (India)

    Deshmukhe, G.V.; Dhargalkar, V.K.; Untawale, A.G.

    The chapter summarizes our present knowledge of the seaweed resources of the Indian Ocean region with regard to the phytogeographical distribution, composition, biomass, utilization, cultivation, conservation and management. The voluminous data...

  13. Arthritis - resources

    Science.gov (United States)

    Resources - arthritis ... The following organizations provide more information on arthritis : American Academy of Orthopaedic Surgeons -- orthoinfo.aaos.org/menus/arthritis.cfm Arthritis Foundation -- www.arthritis.org Centers for Disease Control and Prevention -- www. ...

  14. Mineral resources

    Digital Repository Service at National Institute of Oceanography (India)

    Valsangkar, A.B.

    (placers), biogenous (ooze, limestone) or chemogenous (phosphorites and polymetallic nodules) type. In recent years, hydrothermal deposits, cobalt crust and methane gas hydrates are considered as frontier resources. Their distribution depends upon proximity...

  15. Depression - resources

    Science.gov (United States)

    Resources - depression ... Depression is a medical condition. If you think you may be depressed, see a health care provider. ... following organizations are good sources of information on depression : American Psychological Association -- www.apa.org/topics/depression/ ...

  16. Hemophilia - resources

    Science.gov (United States)

    Resources - hemophilia ... The following organizations provide further information on hemophilia : Centers for Disease Control and Prevention -- www.cdc.gov/ncbddd/hemophilia/index.html National Heart, Lung, and Blood Institute -- www.nhlbi.nih.gov/ ...

  17. Diabetes - resources

    Science.gov (United States)

    Resources - diabetes ... The following sites provide further information on diabetes: American Diabetes Association -- www.diabetes.org Juvenile Diabetes Research Foundation International -- www.jdrf.org National Center for Chronic Disease Prevention and Health Promotion -- ...

  18. Clonorchis sinensis antigens alter hepatic macrophage polarization in vitro and in vivo.

    Science.gov (United States)

    Kim, Eun-Min; Kwak, You Shine; Yi, Myung-Hee; Kim, Ju Yeong; Sohn, Woon-Mok; Yong, Tai-Soon

    2017-05-01

    Clonorchis sinensis infection elicits hepatic inflammation, which can lead to cholangitis, periductal hepatic fibrosis, liver cirrhosis, and even cholangiocarcinoma. Hepatic macrophages are an intrinsic element of both innate and acquired immunity. This study was conducted to demonstrate the dynamics of hepatic macrophage polarization during C. sinensis infection in mice and to identify factors regulating this polarization. Treatment of hepatic macrophages isolated from normal mice with C. sinensis excretory/secretory products (ESPs) resulted in the preferential generation of classically activated hepatic macrophages (M1 macrophages) and the production of pro-inflammatory cytokines. Additionally, cells stimulated with C. sinensis ESPs exhibited changes in cellular morphology. During the early stages of C. sinensis infection, hepatic macrophages preferentially differentiated into M1 macrophages; however, during the C. sinensis mature worm stage, when eggs are released, there were significant increases in the abundance of both M1 macrophages and alternatively activated hepatic macrophages (M2 macrophages). Moreover, there was a further increase in the M2 macrophage count during the fibrotic and cirrhotic stage of infection. Notably, this fibrotic and cirrhotic stage promoted a strong increase in the proportion of Arg-1-producing macrophages (M2 phenotype), which were associated with fibrosis and tissue repair in the liver. Our results suggest that the dynamic polarization of hepatic macrophages as C. sinensis infection progresses is related to the histological lesions present in liver tissue. Hepatic macrophages thus play an important role in local immunity during C. sinensis infection.

  19. Clonorchis sinensis antigens alter hepatic macrophage polarization in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Eun-Min Kim

    2017-05-01

    Full Text Available Clonorchis sinensis infection elicits hepatic inflammation, which can lead to cholangitis, periductal hepatic fibrosis, liver cirrhosis, and even cholangiocarcinoma. Hepatic macrophages are an intrinsic element of both innate and acquired immunity. This study was conducted to demonstrate the dynamics of hepatic macrophage polarization during C. sinensis infection in mice and to identify factors regulating this polarization. Treatment of hepatic macrophages isolated from normal mice with C. sinensis excretory/secretory products (ESPs resulted in the preferential generation of classically activated hepatic macrophages (M1 macrophages and the production of pro-inflammatory cytokines. Additionally, cells stimulated with C. sinensis ESPs exhibited changes in cellular morphology. During the early stages of C. sinensis infection, hepatic macrophages preferentially differentiated into M1 macrophages; however, during the C. sinensis mature worm stage, when eggs are released, there were significant increases in the abundance of both M1 macrophages and alternatively activated hepatic macrophages (M2 macrophages. Moreover, there was a further increase in the M2 macrophage count during the fibrotic and cirrhotic stage of infection. Notably, this fibrotic and cirrhotic stage promoted a strong increase in the proportion of Arg-1-producing macrophages (M2 phenotype, which were associated with fibrosis and tissue repair in the liver. Our results suggest that the dynamic polarization of hepatic macrophages as C. sinensis infection progresses is related to the histological lesions present in liver tissue. Hepatic macrophages thus play an important role in local immunity during C. sinensis infection.

  20. Forest Resources

    Energy Technology Data Exchange (ETDEWEB)

    None

    2016-06-01

    Forest biomass is an abundant biomass feedstock that complements the conventional forest use of wood for paper and wood materials. It may be utilized for bioenergy production, such as heat and electricity, as well as for biofuels and a variety of bioproducts, such as industrial chemicals, textiles, and other renewable materials. The resources within the 2016 Billion-Ton Report include primary forest resources, which are taken directly from timberland-only forests, removed from the land, and taken to the roadside.

  1. Revisiting mouse peritoneal macrophages: heterogeneity, development and function

    Directory of Open Access Journals (Sweden)

    Alexandra Dos Anjos Cassado

    2015-05-01

    Full Text Available Tissue macrophages play a crucial role in the maintenance of tissue homeostasis and also contribute to inflammatory and reparatory responses during pathogenic infection and tissue injury. The high heterogeneity of these macrophages is consistent with their adaptation to distinct tissue environments and specialization to develop niche-specific functions. Although peritoneal macrophages are one of best-studied macrophage populations, only recently it was demonstrated the co-existence of two subsets in mouse PerC, which exhibit distinct phenotypes, functions and origins. These macrophage subsets have been classified according to their morphology as LPMs (large peritoneal macrophages and SPMs (small peritoneal macrophages. LPMs, the most abundant subset under steady-state conditions, express high levels of F4/80 and low levels of class II molecules of the major histocompatibility complex (MHC. LPMs appear to be originated from embriogenic precursors, and their maintenance in PerC is regulated by expression of specific transcription factors and tissue-derived signals. Conversely, SPMs, a minor subset in unstimulated PerC, have a F4/80lowMHC-IIhigh phenotype and are generated from bone-marrow-derived myeloid precursors. In response to infectious or inflammatory stimuli, the cellular composition of PerC is dramatically altered, where LPMs disappear and SPMs become the prevalent population together with their precursor, the inflammatory monocyte. SPMs appear to be the major source of inflammatory mediators in PerC during infection whereas LPMs contribute for gut-associated lymphoid tissue (GALT-independent and retinoic acid-dependent IgA production by peritoneal B-1 cells. In the last years, considerable efforts have been made to broaden our understanding of LPM and SPM origin, transcriptional regulation and functional profile. This review addresses these issues, focusing on the impact of tissue-derived signals and external stimulation in the complex

  2. Gene expression in IFN-g-activated murine macrophages

    Directory of Open Access Journals (Sweden)

    Pereira C.A.

    2004-01-01

    Full Text Available Macrophages are critical for natural immunity and play a central role in specific acquired immunity. The IFN-gamma activation of macrophages derived from A/J or BALB/c mice yielded two different patterns of antiviral state in murine hepatitis virus 3 infection, which were related to a down-regulation of the main virus receptor. Using cDNA hybridization to evaluate mRNA accumulation in the cells, we were able to identify several genes that are differently up- or down-regulated by IFN-gamma in A/J (267 and 266 genes, respectively, up- and down-regulated or BALB/c (297 and 58 genes, respectively, up- and down-regulated mouse macrophages. Macrophages from mice with different genetic backgrounds behave differently at the molecular level and comparison of the patterns of non-activated and IFN-gamma-activated A/J or BALB/c mouse macrophages revealed, for instance, an up-regulation and a down-regulation of genes coding for biological functions such as enzymatic reactions, nucleic acid synthesis and transport, protein synthesis, transport and metabolism, cytoskeleton arrangement and extracellular matrix, phagocytosis, resistance and susceptibility to infection and tumors, inflammation, and cell differentiation or activation. The present data are reported in order to facilitate future correlation of proteomic/transcriptomic findings as well as of results obtained from a classical approach for the understanding of biological phenomena. The possible implication of the role of some of the gene products relevant to macrophage biology can now be further scrutinized. In this respect, a down-regulation of the main murine hepatitis virus 3 receptor gene was detected only in IFN-gamma-activated macrophages of resistant mice.

  3. Decreased inducibility of TNF expression in lipid-loaded macrophages

    Directory of Open Access Journals (Sweden)

    Kallin Bengt

    2002-10-01

    Full Text Available Abstract Background Inflammation and immune responses are considered to be very important in the pathogenesis of atherosclerosis. Lipid accumulation in macrophages of the arterial intima is a characteristic feature of atherosclerosis which can influence the inflammatory potential of macrophages. We studied the effects of lipid loading on the regulation of TNF expression in human monocyte-derived macrophages. Results In macrophages incubated with acetylated low density lipoprotein (ac-LDL for 2 days, mRNA expression of TNF in cells stimulated with TNF decreased by 75%. In cell cultures stimulated over night with IL-1β, lipid loading decreased secretion of TNF into culture medium by 48%. These results suggest that lipid accumulation in macrophages makes them less responsive to inflammatory stimuli. Decreased basal activity and inducibility of transcription factor AP-1 was observed in lipid-loaded cells, suggesting a mechanism for the suppression of cytokine expression. NF-κB binding activity and inducibility were only marginally affected by ac-LDL. LDL and ac-LDL did not activate PPARγ. In contrast, oxidized LDL stimulated AP-1 and PPARγ but inhibited NF-κB, indicating that the effects of lipid loading with ac-LDL were not due to oxidation of lipids. Conclusions Accumulation of lipid, mainly cholesterol, results in down-regulation of TNF expression in macrophages. Since monocytes are known to be activated by cell adhesion, these results suggest that foam cells in atherosclerotic plaques may contribute less potently to an inflammatory reaction than newly arrived monocytes/macrophages.

  4. 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.

  5. Cathepsin E deficiency impairs autophagic proteolysis in macrophages.

    Directory of Open Access Journals (Sweden)

    Takayuki Tsukuba

    Full Text Available Cathepsin E is an endosomal aspartic proteinase that is predominantly expressed in immune-related cells. Recently, we showed that macrophages derived from cathepsin E-deficient (CatE(-/- mice display accumulation of lysosomal membrane proteins and abnormal membrane trafficking. In this study, we demonstrated that CatE(-/- macrophages exhibit abnormalities in autophagy, a bulk degradation system for aggregated proteins and damaged organelles. CatE(-/- macrophages showed increased accumulation of autophagy marker proteins such as LC3 and p62, and polyubiquitinated proteins. Cathepsin E deficiency also altered autophagy-related signaling pathways such as those mediated by the mammalian target of rapamycin (mTOR, Akt, and extracellular signal-related kinase (ERK. Furthermore, immunofluorescence microscopy analyses showed that LC3-positive vesicles were merged with acidic compartments in wild-type macrophages, but not in CatE(-/- macrophages, indicating inhibition of fusion of autophagosome with lysosomes in CatE(-/- cells. Delayed degradation of LC3 protein was also observed under starvation-induced conditions. Since the autophagy system is involved in the degradation of damaged mitochondria, we examined the accumulation of damaged mitochondria in CatE(-/- macrophages. Several mitochondrial abnormalities such as decreased intracellular ATP levels, depolarized mitochondrial membrane potential, and decreased mitochondrial oxygen consumption were observed. Such mitochondrial dysfunction likely led to the accompanying oxidative stress. In fact, CatE(-/- macrophages showed increased reactive oxygen species (ROS production and up-regulation of oxidized peroxiredoxin-6, but decreased antioxidant glutathione. These results indicate that cathepsin E deficiency causes autophagy impairment concomitantly with increased aberrant mitochondria as well as increased oxidative stress.

  6. Photochemical internalization enhanced macrophage delivered chemotherapy.

    Science.gov (United States)

    Shin, Diane; Christie, Catherine; Ju, David; Nair, Rohit Kumar; Molina, Stephanie; Berg, Kristian; Krasieva, Tatiana B; Madsen, Steen J; Hirschberg, Henry

    2018-03-01

    Macrophage (Ma) vectorization of chemotherapeutic drugs has the advantage for cancer therapy in that it can actively target and maintain an elevated concentration of drugs at the tumor site, preventing their spread into healthy tissue. A potential drawback is the inability to deliver a sufficient number of drug-loaded Ma into the tumor, thus limiting the amount of active drug delivered. This study examined the ability of photochemical internalization (PCI) to enhance the efficacy of released drug by Ma transport. Tumor spheroids consisting of either F98 rat glioma cells or F98 cells combined with a subpopulation of empty or doxorubicin (DOX)-loaded mouse Ma (RAW264.7) were used as in vitro tumor models. PCI was performed with the photosensitizer AlPcS 2a and laser irradiation at 670 nm. RAW264.7 Ma pulsed with DOX released the majority of the incorporated DOX within two hours of incubation. PCI significantly increased the toxicity of DOX either as pure drug or derived from monolayers of DOX-loaded Ma. Significant growth inhibition of hybrid spheroids was also observed with PCI even at subpopulations of DOX-loaded Ma as low as 11% of the total initial hybrid spheroid cell number. Results show that RAW264.7 Ma, pulsed with DOX, could effectively incorporate and release DOX. PCI significantly increased the ability of both free and Ma-released DOX to inhibit the growth of tumor spheroids in vitro. The growth of F98 + DOX loaded Ma hybrid spheroids were synergistically reduced by PCI, compared to either photodynamic therapy or released DOX acting alone. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Native low-density lipoprotein uptake by macrophage colony-stimulating factor-differentiated human macrophages is mediated by macropinocytosis and micropinocytosis.

    Science.gov (United States)

    Anzinger, Joshua J; Chang, Janet; Xu, Qing; Buono, Chiara; Li, Yifu; Leyva, Francisco J; Park, Bum-Chan; Greene, Lois E; Kruth, Howard S

    2010-10-01

    To examine the pinocytotic pathways mediating native low-density lipoprotein (LDL) uptake by human macrophage colony-stimulating factor-differentiated macrophages (the predominant macrophage phenotype in human atherosclerotic plaques). We identified the kinase inhibitor SU6656 and the Rho GTPase inhibitor toxin B as inhibitors of macrophage fluid-phase pinocytosis of LDL. Assessment of macropinocytosis by time-lapse microscopy revealed that both drugs almost completely inhibited macropinocytosis, although LDL uptake and cholesterol accumulation by macrophages were only partially inhibited (approximately 40%) by these agents. Therefore, we investigated the role of micropinocytosis in mediating LDL uptake in macrophages and identified bafilomycin A1 as an additional partial inhibitor (approximately 40%) of macrophage LDL uptake that targeted micropinocytosis. When macrophages were incubated with both bafilomycin A1 and SU6656, inhibition of LDL uptake was additive (reaching 80%), showing that these inhibitors target different pathways. Microscopic analysis of fluid-phase uptake pathways in these macrophages confirmed that LDL uptake occurs through both macropinocytosis and micropinocytosis. Our findings show that human macrophage colony-stimulating factor-differentiated macrophages take up native LDL by macropinocytosis and micropinocytosis, underscoring the importance of both pathways in mediating LDL uptake by these cells.

  8. TNF-alpha, produced by feline infectious peritonitis virus (FIPV)-infected macrophages, upregulates expression of type II FIPV receptor feline aminopeptidase N in feline macrophages.

    Science.gov (United States)

    Takano, Tomomi; Hohdatsu, Tsutomu; Toda, Ayako; Tanabe, Maki; Koyama, Hiroyuki

    2007-07-20

    The pathogenicity of feline infectious peritonitis virus (FIPV) is known to depend on macrophage tropism, and this macrophage infection is enhanced by mediation via anti-S antibody (antibody-dependent enhancement, ADE). In this study, we found that TNF-alpha production was increased with viral replication in macrophages inoculated with a mixture of FIPV and anti-S antibody, and demonstrated that this culture supernatant had feline PBMC apoptosis-inducing activity. We also demonstrated that the expression level of the FIPV virus receptor, feline aminopeptidase N (fAPN), was increased in macrophages of FIP cats. For upregulation of TNF-alpha and fAPN in macrophages, viral replication in macrophages is necessary, and their expressions were increased by ADE of FIPV infection. It was demonstrated that a heat-resistant fAPN-inducing factor was present in the culture supernatant of FIPV-infected macrophages, and this factor was TNF-alpha: fAPN expression was upregulated in recombinant feline TNF-alpha-treated macrophages, and FIPV infectivity was increased in these macrophages. These findings suggested that FIPV replication in macrophages increases TNF-alpha production in macrophages, and the produced TNF-alpha acts and upregulates fAPN expression, increasing FIPV sensitivity.

  9. Human Subcutaneous Tissue Response to Glucose Sensors: Macrophages Accumulation Impact on Sensor Accuracy.

    Science.gov (United States)

    Rigla, Mercedes; Pons, Belén; Rebasa, Pere; Luna, Alexis; Pozo, Francisco Javier; Caixàs, Assumpta; Villaplana, Maria; Subías, David; Bella, Maria Rosa; Combalia, Neus

    2018-04-01

    Subcutaneous (s.c.) glucose sensors have become a key component in type 1 diabetes management. However, their usability is limited by the impact of foreign body response (FBR) on their duration, reliability, and accuracy. Our study gives the first description of human acute and subacute s.c. response to glucose sensors, showing the changes observed in the sensor surface, the inflammatory cells involved in the FBR and their relationship with sensor performance. Twelve obese patients (seven type 2 diabetes) underwent two abdominal biopsies comprising the surrounding area where they had worn two glucose sensors: the first one inserted 7 days before and the second one 24 h before biopsy procedure. Samples were processed and studied to describe tissue changes by two independent pathologists (blind regarding sensor duration). Macrophages quantification was studied by immunohistochemistry methods in the area surrounding the sensor (CD68, CD163). Sensor surface changes were studied by scanning electron microscopy. Seven-day continuous glucose monitoring records were considered inaccurate when mean absolute relative difference was higher than 10%. Pathologists were able to correctly classify all the biopsies regarding sensor duration. Acute response (24 h) was characterized by the presence of neutrophils while macrophages were the main cell involved in subacute inflammation. The number of macrophages around the insertion hole was higher for less accurate sensors compared with those performing more accurately (32.6 ± 14 vs. 10.6 ± 1 cells/0.01 mm 2 ; P sensor-tissue interface is related with decrease in accuracy of the glucose measure.

  10. Characteristics of adipose tissue macrophages and macrophage-derived insulin-like growth factor-1 in virus-induced obesity.

    Science.gov (United States)

    Park, S; Park, H-L; Lee, S-Y; Nam, J-H

    2016-03-01

    Various pathogens are implicated in the induction of obesity. Previous studies have confirmed that human adenovirus 36 (Ad36) is associated with increased adiposity, improved glycemic control and induction of inflammation. The Ad36-induced inflammation is reflected in the infiltration of macrophages into adipose tissue. However, the characteristics and role of adipose tissue macrophages (ATMs) and macrophage-secreted factors in virus-induced obesity (VIO) are unclear. Although insulin-like growth factor-1 (IGF-1) is involved in obesity metabolism, the contribution of IGF secreted by macrophages in VIO has not been studied. Four-week-old male mice were studied 1 week and 12 weeks after Ad36 infection for determining the characteristics of ATMs in VIO and diet-induced obesity (DIO). In addition, macrophage-specific IGF-1-deficient (MIKO) mice were used to study the involvement of IGF-1 in VIO. In the early stage of VIO (1 week after Ad36 infection), the M1 ATM sub-population increased, which increased the M1/M2 ratio, whereas DIO did not cause this change. In the late stage of VIO (12 weeks after Ad36 infection), the M1/M2 ratio did not change because the M1 and M2 ATM sub-populations increased to a similar extent, despite an increase in adiposity. By contrast, DIO increased the M1/M2 ratio. In addition, VIO in wild-type mice upregulated angiogenesis in adipose tissue and improved glycemic control. However, MIKO mice showed no increase in adiposity, angiogenesis, infiltration of macrophages into adipose tissue, or improvement in glycemic control after Ad36 infection. These data suggest that IGF-1 secreted by macrophages may contribute to hyperplasia and hypertrophy in adipose tissue by increasing angiogenesis, which helps to maintain the 'adipose tissue robustness'.

  11. Comparative analysis of the internalization of the macrophage receptor sialoadhesin in human and mouse primary macrophages and cell lines.

    Science.gov (United States)

    De Schryver, Marjorie; Leemans, Annelies; Pintelon, Isabel; Cappoen, Davie; Maes, Louis; Caljon, Guy; Cos, Paul; Delputte, Peter L

    2017-06-01

    Sialoadhesin (Sn) is a surface receptor expressed on resident macrophages with the ability to bind with sialic acids. During inflammation, an upregulation of Sn is observed. Upon binding of monoclonal antibodies to Sn, the receptor becomes internalized and this has been observed in multiple species. The latter characteristic, combined with the strong upregulation of Sn on inflammatory macrophages and the fact that Sn-positive macrophages contribute to certain inflammatory diseases, makes Sn an interesting entry portal for phenotype-modulating or cytotoxic drugs. Such drugs or toxins can be linked to Sn-specific antibodies which should enable their targeted uptake by macrophages. However, the activity of such drugs depends not only on their internalization but also on the intracellular trafficking and final fate in the endolysosomal system. Although information is available for porcine Sn, the detailed mechanisms of human and mouse Sn internalization and subsequent intracellular trafficking are currently unknown. To allow development of Sn-targeted therapies, differences across species and cellular background need to be characterized in more detail. In the current report, we show that internalization of human and mouse Sn is dynamin-dependent and clathrin-mediated, both in primary macrophages and CHO cell lines expressing a recombinant Sn. In primary macrophages, internalized Sn-specific F(ab') 2 fragments are located mostly in the early endosomes. With Fc containing Sn-specific antibodies, there is a slight shift towards lysosomal localization in mouse macrophages, possibly because of an interaction with Fc receptors. Surprisingly, in CHO cell lines expressing Sn, there is a predominant lysosomal localization. Our results show that the mechanism of Sn internalization and intracellular trafficking is concurrent in the tested species. The cellular background in which Sn is expressed and the type of antibody used can affect the intracellular fate, which in turn can

  12. Suppression of developmental anomalies by maternal macrophages in mice

    International Nuclear Information System (INIS)

    Nomura, T.; Hata, S.; Kusafuka, T.

    1990-01-01

    We tested whether nonspecific tumoricidal immune cells can suppress congenital malformations by killing precursor cells destined to cause such defects. Pretreatment of pregnant ICR mice with synthetic (Pyran copolymer) and biological (Bacillus Calmette-Guerin) agents significantly suppressed radiation- and chemical-induced congenital malformations (cleft palate, digit anomalies, tail anomalies, etc.). Such suppressive effects were associated with the activation of maternal macrophages by these agents, but were lost either after the disruption of activated macrophages by supersonic waves or by inhibition of their lysosomal enzyme activity with trypan blue. These results indicate that a live activated macrophage with active lysosomal enzymes can be an effector cell to suppress maldevelopment. A similar reduction by activated macrophages was observed in strain CL/Fr, which has a high spontaneous frequency of cleft lips and palates. Furthermore, Pyran-activated maternal macrophages could pass through the placenta, and enhanced urethane-induced cell killing (but not somatic mutation) in the embryo. It is likely that a maternal immunosurveillance system eliminating preteratogenic cells allows for the replacement with normal totipotent blast cells during the pregnancy to protect abnormal development

  13. Macrophage-secreted factors induce adipocyte inflammation and insulin resistance

    International Nuclear Information System (INIS)

    Permana, Paska A.; Menge, Christopher; Reaven, Peter D.

    2006-01-01

    Macrophage infiltration into adipose tissue increases with obesity, a condition associated with low-grade inflammation and insulin resistance. We investigated the direct effects of macrophage-secreted factors on adipocyte inflammation and insulin resistance. 3T3-L1 adipocytes incubated with media conditioned by RAW264.7 macrophages (RAW-CM) showed dramatically increased transcription of several inflammation-related genes, greater nuclear factor kappa B (NF-κB) activity, and enhanced binding of U937 monocytes. All of these effects were prevented by co-incubation with pyrrolidinedithiocarbamate, an NF-κB inhibitor. Adipocytes incubated with RAW-CM also released more non-esterified fatty acids and this increased lipolysis was not suppressed by insulin. In addition, RAW-CM treatment decreased insulin-stimulated glucose uptake in adipocytes. Taken together, these results indicate that macrophage-secreted factors induce inflammatory responses and reduce insulin responsiveness in adipocytes. These effects of macrophage-secreted factors on adipocytes may contribute significantly to the systemic inflammation and insulin resistance associated with obesity

  14. Macrophage-mediated response to hypoxia in disease

    Directory of Open Access Journals (Sweden)

    Tazzyman S

    2014-11-01

    Full Text Available Simon Tazzyman,1 Craig Murdoch,2 James Yeomans,1 Jack Harrison,1 Munitta Muthana3 1Department of Oncology, 2School of Clinical Dentistry, 3Department of Infection and Immunity, University of Sheffield, Sheffield, UK Abstract: Hypoxia plays a critical role in the pathobiology of various inflamed, diseased tissues, including malignant tumors, atherosclerotic plaques, myocardial infarcts, the synovia of rheumatoid arthritic joints, healing wounds, and sites of bacterial infection. These areas of hypoxia form when the blood supply is occluded and/or the oxygen supply is unable to keep pace with cell growth and/or infiltration of inflammatory cells. Macrophages are ubiquitous in all tissues of the body and exhibit great plasticity, allowing them to perform divergent functions, including, among others, patrolling tissue, combating invading pathogens and tumor cells, orchestrating wound healing, and restoring homeostasis after an inflammatory response. The number of tissue macrophages increases markedly with the onset and progression of many pathological states, with many macrophages accumulating in avascular and necrotic areas, where they are exposed to hypoxia. Recent studies show that these highly versatile cells then respond rapidly to the hypoxia present by altering their expression of a wide array of genes. Here we review the evidence for hypoxia-driven macrophage inflammatory responses in various disease states, and how this influences disease progression and treatment. Keywords: macrophage, hypoxia, inflammation, cytokine

  15. Macrophage sphingolipids are essential for the entry of mycobacteria.

    Science.gov (United States)

    Viswanathan, Gopinath; Jafurulla, Md; Kumar, G Aditya; Raghunand, Tirumalai R; Chattopadhyay, Amitabha

    2018-07-01

    Mycobacteria are intracellular pathogens that can invade and survive within host macrophages. Mycobacterial infections remain a major cause of mortality and morbidity worldwide, with serious concerns of emergence of multi and extensively drug-resistant tuberculosis. While significant advances have been made in identifying mycobacterial virulence determinants, the detailed molecular mechanism of internalization of mycobacteria into host cells remains poorly understood. Although several studies have highlighted the crucial role of sphingolipids in mycobacterial growth, persistence and establishment of infection, the role of sphingolipids in the entry of mycobacteria into host cells is not known. In this work, we explored the role of host membrane sphingolipids in the entry of Mycobacterium smegmatis into J774A.1 macrophages. Our results show that metabolic depletion of sphingolipids in host macrophages results in a significant reduction in the entry of M. smegmatis. Importantly, the entry of Escherichia coli into host macrophages under similar conditions remained invariant, implying the specificity of the requirement of sphingolipids in mycobacterial entry. To the best of our knowledge, our results constitute the first report demonstrating the role of host macrophage sphingolipids in the entry of mycobacteria. Our results could help in the development of novel therapeutic strategies targeting sphingolipid-mediated entry of mycobacteria into host cells. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Peptide secreted by human alveolar macrophages releases neutrophil granule contents

    International Nuclear Information System (INIS)

    MacArthur, C.K.; Miller, E.J.; Cohen, A.B.

    1987-01-01

    A monoclonal antibody was developed against an 8000-kDa enzyme-releasing peptide (ERP) released from human alveolar macrophages. ERP was isolated on an immunoaffinity column containing the antibody bound to staphylococcal protein A-Sepharose, and by autoradiography. Release of ERP from the macrophages is not changed by plastic adherence, phagocytosis, calcium ionophore, or phorbol esters. The peptide was not antigenically similar to interferon-γ, tumor necrosis factor, or interleukin lα or 1β. The release of constituents from azurophilic and specific granules was the main identified biologic function of ERP. ERP was a more effective secretagogue in the untreated neutrophils and f-met-leu-phe was more effective in the cytochalasin B-treated neutrophils. Absorption of ERP from macrophage-conditioned medium removed a small amount of the chemotactic activity; however, the immunopurified peptide was not chemotactic or chemokinetic for neutrophils, and at high concentrations, it suppressed base line chemokinesis. Treatment of washed macrophages with trypsin released active ERP of approximately the same m.w. of spontaneously secreted ERP. These studies showed that human alveolar macrophages release a peptide which is a secretagogue for human neutrophils under conditions which may be encountered in the lungs during certain disease states. Proteolytic enzymes which are free in the lungs may release the peptide and lead to the secretion of neutrophil enzymes

  17. Divergence of macrophage phagocytic and antimicrobial programs in leprosy.

    Science.gov (United States)

    Montoya, Dennis; Cruz, Daniel; Teles, Rosane M B; Lee, Delphine J; Ochoa, Maria Teresa; Krutzik, Stephan R; Chun, Rene; Schenk, Mirjam; Zhang, Xiaoran; Ferguson, Benjamin G; Burdick, Anne E; Sarno, Euzenir N; Rea, Thomas H; Hewison, Martin; Adams, John S; Cheng, Genhong; Modlin, Robert L

    2009-10-22

    Effective innate immunity against many microbial pathogens requires macrophage programs that upregulate phagocytosis and direct antimicrobial pathways, two functions generally assumed to be coordinately regulated. We investigated the regulation of these key functions in human blood-derived macrophages. Interleukin-10 (IL-10) induced the phagocytic pathway, including the C-type lectin CD209 and scavenger receptors, resulting in phagocytosis of mycobacteria and oxidized low-density lipoprotein. IL-15 induced the vitamin D-dependent antimicrobial pathway and CD209, yet the cells were less phagocytic. The differential regulation of macrophage functional programs was confirmed by analysis of leprosy lesions: the macrophage phagocytosis pathway was prominent in the clinically progressive, multibacillary form of the disease, whereas the vitamin D-dependent antimicrobial pathway predominated in the self-limited form and in patients undergoing reversal reactions from the multibacillary to the self-limited form. These data indicate that macrophage programs for phagocytosis and antimicrobial responses are distinct and differentially regulated in innate immunity to bacterial infections.

  18. Protein energy malnutrition increases arginase activity in monocytes and macrophages.

    Science.gov (United States)

    Corware, Karina; Yardley, Vanessa; Mack, Christopher; Schuster, Steffen; Al-Hassi, Hafid; Herath, Shanthi; Bergin, Philip; Modolell, Manuel; Munder, Markus; Müller, Ingrid; Kropf, Pascale

    2014-01-01

    Protein energy malnutrition is commonly associated with immune dysfunctions and is a major factor in susceptibility to infectious diseases. In this study, we evaluated the impact of protein energy malnutrition on the capacity of monocytes and macrophages to upregulate arginase, an enzyme associated with immunosuppression and increased pathogen replication. Our results show that monocytes and macrophages are significantly increased in the bone marrow and blood of mice fed on a protein low diet. No alteration in the capacity of bone marrow derived macrophages isolated from malnourished mice to phagocytose particles, to produce the microbicidal molecule nitric oxide and to kill intracellular Leishmania parasites was detected. However, macrophages and monocytes from malnourished mice express significantly more arginase both in vitro and in vivo. Using an experimental model of visceral leishmaniasis, we show that following protein energy malnutrition, the increased parasite burden measured in the spleen of these mice coincided with increased arginase activity and that macrophages provide a more permissive environment for parasite growth. Taken together, these results identify a novel mechanism in protein energy malnutrition that might contributes to increased susceptibility to infectious diseases by upregulating arginase activity in myeloid cells.

  19. Dopamine receptor activation increases HIV entry into primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Peter J Gaskill

    Full Text Available Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers.

  20. Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

    Science.gov (United States)

    Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

    2014-01-01

    Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

  1. Curcumin enhances human macrophage control of Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Bai, Xiyuan; Oberley-Deegan, Rebecca E; Bai, An; Ovrutsky, Alida R; Kinney, William H; Weaver, Michael; Zhang, Gong; Honda, Jennifer R; Chan, Edward D

    2016-07-01

    With the worldwide emergence of highly drug-resistant tuberculosis (TB), novel agents that have direct antimycobacterial effects or that enhance host immunity are urgently needed. Curcumin is a polyphenol responsible for the bright yellow-orange colour of turmeric, a spice derived from the root of the perennial herb Curcuma longa. Curcumin is a potent inducer of apoptosis-an effector mechanism used by macrophages to kill intracellular Mycobacterium tuberculosis (MTB). An in vitro human macrophage infection model was used to determine the effects of curcumin on MTB survival. We found that curcumin enhanced the clearance of MTB in differentiated THP-1 human monocytes and in primary human alveolar macrophages. We also found that curcumin was an inducer of caspase-3-dependent apoptosis and autophagy. Curcumin mediated these anti-MTB cellular functions, in part, via inhibition of nuclear factor-kappa B (NFκB) activation. Curcumin protects against MTB infection in human macrophages. The host-protective role of curcumin against MTB in macrophages needs confirmation in an animal model; if validated, the immunomodulatory anti-TB effects of curcumin would be less prone to drug resistance development. © 2016 Asian Pacific Society of Respirology.

  2. 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.

  3. Dioscorin isolated from Dioscorea alata activates TLR4-signaling pathways and induces cytokine expression in macrophages.

    Science.gov (United States)

    Fu, Shu-Ling; Hsu, Ya-Hui; Lee, Pei-Yeh; Hou, Wen-Chi; Hung, Ling-Chien; Lin, Chao-Hsiung; Chen, Chiu-Ming; Huang, Yu-Jing

    2006-01-06

    The Toll-like receptor 4 (TLR4)-signaling pathway is crucial for activating both innate and adaptive immunity. TLR4 is a promising molecular target for immune-modulating drugs, and TLR4 agonists are of therapeutic potential for treating immune diseases and cancers. Several medicinal herb-derived components have recently been reported to act via TLR4-dependent pathways, suggesting that medicinal plants are potential resources for identifying TLR4 activators. We have applied a screening procedure to systematically identify herbal constituents that activate TLR4. To exclude possible LPS contamination in these plant-derived components, a LPS inhibitor, polymyxin B, was added during screening. One of the plant components we identified from the screening was dioscorin, the glycoprotein isolated from Dioscorea alata. It induced TLR4-downstream cytokine expression in bone marrow cells isolated from TLR4-functional C3H/HeN mice but not from TLR4-defective C3H/HeJ mice. Dioscorin also stimulated multiple signaling molecules (NF-kappaB, ERK, JNK, and p38) and induced the expression of cytokines (TNF-alpha, IL-1beta, and IL-6) in murine RAW 264.7 macrophages. Furthermore, the ERK, p38, JNK, and NF-kappaB-mediated pathways are all involved in dioscorin-mediated TNF-alpha production. In summary, our results demonstrate that dioscorin is a novel TLR4 activator and induces macrophage activation via typical TLR4-signaling pathways.

  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. Therapeutic potential of regulatory macrophages generated from peritoneal dialysate in adriamycin nephropathy.

    Science.gov (United States)

    Cao, Qi; Wang, Yiping; Wang, Changqi; Wang, Xin M; Lee, Vincent W S; Zheng, Guoping; Zhao, Ye; Alexander, Stephen I; Harris, David C H

    2018-04-01

    Cell therapy using macrophages requires large amounts of cells, which are difficult to collect from patients. Patients undergoing peritoneal dialysis (PD) discard huge numbers of peritoneal macrophages in dialysate daily. Macrophages can be modulated to become regulatory macrophages, which have shown great promise as a therapeutic strategy in experimental kidney disease and human kidney transplantation. This study aimed to examine the potential of using peritoneal macrophages (PMs) from peritoneal dialysate to treat kidney disease. Monocytes/macrophages accounted for >40% of total peritoneal leukocytes in both patients and mice undergoing PD. PMs from patients and mice undergoing PD were more mature than peripheral monocytes/macrophages, as shown by low expression of C-C motif chemokine receptor 2 (CCR2) and morphological changes during in vitro culture. PMs from patients and mice undergoing PD displayed normal macrophage function and could be modulated into a regulatory (M2) phenotype. In vivo, adoptive transfer of peritoneal M2 macrophages derived from PD mice effectively protected against kidney injury in mice with adriamycin nephropathy (AN). Importantly, the transfused peritoneal M2 macrophages maintained their M2 phenotype in kidney of AN mice. In conclusion, PMs derived from patients and mice undergoing PD exhibited conventional macrophage features. Peritoneal M2 macrophages derived from PD mice are able to reduce kidney injury in AN, suggesting that peritoneal macrophages from patients undergoing PD may have the potential for clinical therapeutic application.

  6. 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.

  7. Preparation of guinea pig macrophage for electrophoretic experiments in space

    Science.gov (United States)

    1979-01-01

    Methods of storage and cultivation of macrophage cells in preparation for space experiments were investigated. Results show that freezing and thawing immediately after extraction did not cause any change in viability or electrophoretic mobility of the cells. A prolonged storage at -80 C did cause cell damage as indicated by a 95% reduction in variable cells. Cell damage was decreased when Glycerol or Dimethyl Sulfoxide (DMSO) was added as a cryogenic protective agent. A 100% viability was observed in cultivation experiments after two weeks due to the additional serum. Results from gamma-glutamyl transpeptidase study showed a zero activity rate. It is suggested that a flat stationary field be used for the collection and use of macrophage. It was found that a 24-hour delay in obtaining macrophage cells helps to maintain a pure culture.

  8. Angiogenic potential of human macrophages on electrospun bioresorbable vascular grafts

    Energy Technology Data Exchange (ETDEWEB)

    Garg, K; Sell, S A; Madurantakam, P; Bowlin, G L, E-mail: glbowlin@vcu.ed [Virginia Commonwealth University, Richmond, VA 23284 (United States)

    2009-06-15

    The aim of this study was to investigate macrophage interactions with electrospun scaffolds and quantify the expression of key angiogenic growth factors in vitro. This study will further help in evaluating the potential of these electrospun constructs as vascular grafts for tissue repair and regeneration in situ. Human peripheral blood macrophages were seeded in serum free media on electrospun (10 mm) discs of polydioxanone (PDO), elastin and PDO:elastin blends (50:50, 70:30 and 90:10). The growth factor secretion was analyzed by ELISA. Macrophages produced high levels of vascular endothelial growth factor and acidic fibroblast growth factor. Transforming growth factor beta-1 (TGF-beta1) secretion was relatively low and there was negligible production of basic fibroblast growth factor. Therefore, it can be anticipated that these scaffolds will support tissue regeneration and angiogenesis. (communication)

  9. Periodontitis-activated monocytes/macrophages cause aortic inflammation

    Science.gov (United States)

    Miyajima, Shin-ichi; Naruse, Keiko; Kobayashi, Yasuko; Nakamura, Nobuhisa; Nishikawa, Toru; Adachi, Kei; Suzuki, Yuki; Kikuchi, Takeshi; Mitani, Akio; Mizutani, Makoto; Ohno, Norikazu; Noguchi, Toshihide; Matsubara, Tatsuaki

    2014-01-01

    A relationship between periodontal disease and atherosclerosis has been suggested by epidemiological studies. Ligature-induced experimental periodontitis is an adequate model for clinical periodontitis, which starts from plaque accumulation, followed by inflammation in the periodontal tissue. Here we have demonstrated using a ligature-induced periodontitis model that periodontitis activates monocytes/macrophages, which subsequently circulate in the blood and adhere to vascular endothelial cells without altering the serum TNF-α concentration. Adherent monocytes/macrophages induced NF-κB activation and VCAM-1 expression in the endothelium and increased the expression of the TNF-α signaling cascade in the aorta. Peripheral blood-derived mononuclear cells from rats with experimental periodontitis showed enhanced adhesion and increased NF-κB/VCAM-1 in cultured vascular endothelial cells. Our results suggest that periodontitis triggers the initial pathogenesis of atherosclerosis, inflammation of the vasculature, through activating monocytes/macrophages. PMID:24893991

  10. Effect of irradiation on lysosomal enzyme activation in cultured macrophages

    International Nuclear Information System (INIS)

    Clarke, C.; Wills, E.D.

    1980-01-01

    The effect of γrays on lysosomal enzyme activity of normal and immune macrophages of DBA/2 mice cultured in vitro has been studied. A dose of 500 rad did not significantly affect lysosomal enzyme activity 3 hours after irradiation but caused the activity to increase to 1.4 times the control value 22.5 hours after irradiation. 22.5 hours after a dose of 3000 rad the enzyme activity increased to 2.5 times the control. Lysosomal enzyme activity of the macrophages was also markedly increased by immunization of the mice with D lymphoma cells, before culture in vitro, but irradiation of these cells with a dose of 500 rad caused a further increase in lysosomal enzyme activity. The results indicate that immunization and irradiation both cause stimulation of lysosomal enzyme activity in macrophages but that the mechanisms of activation are unlikely to be identical. (author)

  11. Incorporation of bacterial peptidoglycan constituents into macrophage lipids during phagocytosis

    International Nuclear Information System (INIS)

    Polanski, M.

    1987-01-01

    Bacillus subtilis radiolabeled cell walls were incubated with the macrophage cell line RAW264 in order to determine whether a peptidoglycan fragment were subsequently maintained on a macrophage lipid. Specifically, cell walls were radiolabeled in their glucosamine, muramic acid and alanine residues with D-[1- 3 H] glucosamine and L[U- 14 C]alanine. Following encounter with these radiolabeled cell walls, macrophages were collected and subjected to lipid extraction procedures. Further fractionation produced a phosphatidylethanolamine co-migrating lipid which upon hydrolysis and amino acid analysis revealed radiolabeled muramic acid, glucosamine, and alanine residues. These residues were shown to form a common fragment since the aqueous soluble material obtained after saponification of the crude lipid extract eluted as a single peak following gel permeation chromatography. Saponification destroyed the TLC mobility of the lipid showing that the fragment was covalently attached to the lipid

  12. Teaching Resources

    Science.gov (United States)

    Physics?" Poster Pamphlets/Books/SPIN-UP Resources Making and Sustaining Changes in Undergraduate AAPT.org - American Association of Physics Teachers Skip to content Skip to navigation Skip to local navigation AAPT - American Association of Physics Teachers Go Sign In / Online Services Join

  13. Resource Mobilization

    International Development Research Centre (IDRC) Digital Library (Canada)

    constitute endorsement of the product and is given only for information. ..... point where they could significantly impact an organization's financial viability. This alternative ... putting in place internal systems and processes that enable the resource .... control over the incorporation of non-profit organizations. ..... Accounting.

  14. Resource Mobilization

    International Development Research Centre (IDRC) Digital Library (Canada)

    Annex 1: The Scoping Study on Donor Funding for. Development Research in ... publication of the Resource Mobilization: A Practical Guide for Research .... applied the concept or technique, which validates the practical application of ... some other staff member would write up a grant application addressed to one, two, or a ...

  15. Macrophage expression in acute radiation colitis in rats

    International Nuclear Information System (INIS)

    Tadami, Tokuma; Shichijo, Kazuko; Matsuu, Mutsumi; Niino, Daisuke; Nakayama, Toshiyuki; Nakashima, Masahiro; Sekine, Ichiro

    2003-01-01

    Although radiation therapy is important in the treatment of tumors in pelvic and abdominal region, it may cause radiation injury as a side effect. But there is no effective way of preventing or curing the damages. The mechanism of acute radiation colitis has not been elucidated yet. Our previous reports have revealed that X-ray irradiation induce apoptosis of epithelial stem cells in colon. Then a hypothesis of the radiation colitis can be put forward, DNA damage by irradiation, apoptosis of mucosal epithelial stem cells and degeneration of epithelial gland structure, macrophages phagocyte the debris, being activated and secreting various inflammatory cytokines, infiltration of inflammatory cells. Several recent reports show that macrophages may play an important role in the process of inflammatory bowel diseases such ulcerative colitis or Crohn's disease. We studied radiation colitis using rat animal models. Male Wister rats were irradiated by a single fraction dose of 22.5 Gy X-ray at laparotomy, shielding except for an approximately 2.5 cm length of rectum. Histological changes and macrophage accumulation in the rectum mucosa were evaluated by immunohistochemistry and western blot method with the specimens which were taken on the 1, 2, 3, 4, 5, 6, 7, 10, and 14th day after irradiation. Severe macrophage accumulation in the lamina propria of the rectum was observed on the 5th day. At the same time, severe destruction of mucosal structure and inflammatory cells infiltration were also observed. Based on the potent pro-inflammatory cytokine producing effects of macrophage in rat and the increased expression in inflammatory bowel disease patients, speculate that intervention in the macrophage-cytokine network could form a future target for the treatment of acute radiation colitis. (author)

  16. Microbial stasis of Leishmania enriettii in activated guinea pig macrophages

    International Nuclear Information System (INIS)

    Groocock, C.M.; Soulsby, E.J.L.

    1980-01-01

    Peritoneal exudate cells (PEC) from Leishmania-sensitized guinea pigs were cultured in vitro in the presence (activated) or absence (non-activated) of leishmanial antigen for 24 or 48 hours. These were then labelled with 51 Cr and challenged with 125 I-labelled promastigotes. The changing relationship between the macrophage and the parasite was monitored by observing changes in the ratio of the cell-associated isotopes. Highly significant differences in the ratio change developed during culture. These differences were a result of the activated cultures showing a higher release of 51 Cr and a lower release of 125 I when compared with the non-activated cells, at 12 hours the percentage release of 125 I from the parasite within the activated macrophage was fourfold less than that released by parasites within non-activated cells (9.2% versus 38.3%) and tenfold less than that released from glutaraldehyde-killed organisms phagocytosed by activated macrophages (91.6%). These studies indicate that stasis rather than killing of leishmaniae occurs in the activated macrophage in vitro. Parallel experiments evaluated by the visual counting of leishmaniae within the macrophages support these data. PEC from tuberculin-sensitized guinea pigs activated in vitro by purified protein derivative showed little or no activity against leishmaniae, indicating a specific requirement for this microbial stasis by activated macrophages. As a corollary of this, peritoneal exudate lymphocytes separated from the same preparations of PEC were shown to be specifically reactive to leishmanial antigen by transformation and incorporation of 3 H-thymidine. (author)

  17. Dysregulation of Macrophage Activation Profiles by Engineered Nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Kodali, Vamsi; Littke, Matthew H.; Tilton, Susan C.; Teeguarden, Justin G.; Shi, Liang; Frevert, Charles W.; Wang, Wei; Pounds, Joel G.; Thrall, Brian D.

    2013-08-27

    Although the potential human health impacts from exposure to engineered nanoparticles (ENPs) are uncertain, past epidemiological studies have established correlations between exposure to ambient air pollution particulates and the incidence of pneumonia and lung infections. Using amorphous silica and superparamagnetic iron oxide (SPIO) as model high production volume ENPs, we examined how macrophage activation by bacterial lipopolysaccharide (LPS) or the lung pathogen Streptococcus pneumoniae is altered by ENP pretreatment. Neither silica nor SPIO treatment elicited direct cytotoxic or pro-inflammatory effects in bone marrow-derived macrophages. However, pretreatment of macrophages with SPIO caused extensive reprogramming of nearly 500 genes regulated in response to LPS challenge, hallmarked by exaggerated activation of oxidative stress response pathways and suppressed activation of both pro- and anti-inflammatory pathways. Silica pretreatment altered regulation of only 67 genes, but there was strong correlation with gene sets affected by SPIO. Macrophages exposed to SPIO displayed a phenotype suggesting an impaired ability to transition from an M1 to M2-like activation state, characterized by suppressed IL-10 induction, enhanced TNFα production, and diminished phagocytic activity toward S. pneumoniae. Studies in macrophages deficient in scavenger receptor A (SR-A) showed SR-A participates in cell uptake of both the ENPs and S. pneumonia and co-regulates the anti-inflammatory IL-10 pathway. Thus, mechanisms for dysregulation of innate immunity exist by virtue that common receptor recognition pathways are used by some ENPs and pathogenic bacteria, although the extent of transcriptional reprogramming of macrophage function depends on the physicochemical properties of the ENP after internalization. Our results also illustrate that biological effects of ENPs may be indirectly manifested only after challenging normal cell function. Finally, nanotoxicology screening

  18. Macrophage polarization alters the expression and sulfation pattern of glycosaminoglycans.

    Science.gov (United States)

    Martinez, Pierre; Denys, Agnès; Delos, Maxime; Sikora, Anne-Sophie; Carpentier, Mathieu; Julien, Sylvain; Pestel, Joël; Allain, Fabrice

    2015-05-01

    Macrophages are major cells of inflammatory process and take part in a large number of physiological and pathological processes. According to tissue environment, they can polarize into pro-inflammatory (M1) or alternative (M2) cells. Although many evidences have hinted to a potential role of cell-surface glycosaminoglycans (GAGs) in the functions of macrophages, the effect of M1 or M2 polarization on the biosynthesis of these polysaccharides has not been investigated so far. GAGs are composed of repeat sulfated disaccharide units. Heparan (HS) and chondroitin/dermatan sulfates (CS/DS) are the major GAGs expressed at the cell membrane. They are involved in numerous biological processes, which rely on their ability to selectively interact with a large panel of proteins. More than 20 genes encoding sulfotransferases have been implicated in HS and CS/DS biosynthesis, and the functional repertoire of HS and CS/DS has been related to the expression of these isoenzymes. In this study, we analyzed the expression of sulfotransferases as a response to macrophage polarization. We found that M1 and M2 activation drastically modified the profiles of expression of numerous HS and CS/DS sulfotransferases. This was accompanied by the expression of GAGs with distinct structural features. We then demonstrated that GAGs of M2 macrophages were efficient to present fibroblast growth factor-2 in an assay of tumor cell proliferation, thus indicating that changes in GAG structure may contribute to the functions of polarized macrophages. Altogether, our findings suggest a regulatory mechanism in which fine modifications in GAG biosynthesis may participate to the plasticity of macrophage functions. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Murine macrophage heparanase: inhibition and comparison with metastatic tumor cells

    International Nuclear Information System (INIS)

    Savion, N.; Disatnik, M.H.; Nevo, Z.

    1987-01-01

    Circulating macrophages and metastatic tumor cells can penetrate the vascular endothelium and migrate from the circulatory system to extravascular compartments. Both activated murine macrophages and different metastatic tumor cells attach, invade, and penetrate confluent vascular endothelial cell monolayer in vitro, by degrading heparan sulfate proteoglycans in the subendothelial extracellular matrix. The sensitivity of the enzymes from the various sources degrading the heparan sulfate proteoglycan was challenged and compared by a series of inhibitors. Activated macrophages demonstrate a heparanase with an endoglycosidase activity that cleaves from the [ 35 S]O 4 - -labeled heparan sulfate proteoglycans of the extracellular matrix 10 kDa glycosaminoglycan fragments. The degradation of [ 35 S]O 4 - -labeled extracellular matrix proteoglycans by the macrophages' heparanase is significantly inhibited in the presence of heparan sulfate (10μg/ml), arteparon (10μg/ml), and heparin at a concentration of 3 μg/ml. Degradation of this heparan sulfate proteoglycan is a two-step sequential process involving protease activity followed by heparanase activity. B16-BL6 metastatic melanoma cell heparanase, which is also a cell-associated enzyme, was inhibited by heparin to the same extent as the macrophage haparanase. On the other hand, heparanase of the highly metastatic variant (ESb) of a methylcholanthrene-induced T lymphoma, which is an extracellular enzyme released by the cells to the incubation medium, was more sensitive to heparin and arteparon than the macrophages' heparanase. These results may indicate the potential use of heparin or other glycosaminoglycans as specific and differential inhibitors for the formation in certain cases of blood-borne tumor metastasis

  20. Toxicity of silver nanoparticles in human macrophages: uptake, intracellular distribution and cellular responses

    Science.gov (United States)

    Haase, A.; Tentschert, J.; Jungnickel, H.; Graf, P.; Mantion, A.; Draude, F.; Plendl, J.; Goetz, M. E.; Galla, S.; Mašić, A.; Thuenemann, A. F.; Taubert, A.; Arlinghaus, H. F.; Luch, A.

    2011-07-01

    Silver nanoparticles (SNP) are among the most commercialized nanoparticles worldwide. They can be found in many diverse products, mostly because of their antibacterial properties. Despite its widespread use only little data on possible adverse health effects exist. It is difficult to compare biological data from different studies due to the great variety in sizes, coatings or shapes of the particles. Here, we applied a novel synthesis approach to obtain SNP, which are covalently stabilized by a small peptide. This enables a tight control of both size and shape. We applied these SNP in two different sizes of 20 or 40 nm (Ag20Pep and Ag40Pep) and analyzed responses of THP-1-derived human macrophages. Similar gold nanoparticles with the same coating (Au20Pep) were used for comparison and found to be non-toxic. We assessed the cytotoxicity of particles and confirmed their cellular uptake via transmission electron microscopy and confocal Raman microscopy. Importantly a majority of the SNP could be detected as individual particles spread throughout the cells. Furthermore we studied several types of oxidative stress related responses such as induction of heme oxygenase I or formation of protein carbonyls. In summary, our data demonstrate that even low doses of SNP exerted adverse effects in human macrophages.