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      Call for Papers: Epidemiology and Health Impacts of Neuroendocrine Tumors

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      About Neuroendocrinology: 3.2 Impact Factor I 8.3 CiteScore I 1.009 Scimago Journal & Country Rank (SJR)

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      Cultured Human Adult Microglia from Different Donors Display Stable Cytokine, Chemokine and Growth Factor Gene Profiles but Respond Differently to a Pro-Inflammatory Stimulus

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          Abstract

          Objectives: Brain microglia are highly responsive cells in the central nervous system that exert key functions in host defense as well as in neuroprotection and regeneration. In this study the gene expression profiles for 268 cytokines, chemokines, growth factors and their receptors were examined in cultures of purified human adult microglia, using cDNA array profiling. Methods: Microglia from 9 different donors were compared, also following challenge of such microglia with the pro-inflammatory cytokines TNF-α and IFN-γ. Results: A stable pattern was observed of genes abundantly expressed in the different cultures under standard conditions. Genes abundantly expressed in all microglia cultures include CCL2 (MCP-1), thymosin β-10, migration-inhibitory factor-related protein 8 (MRP8), MRP14, corticotropin-releasing factor receptor 1 and endothelin 2. Abundant gene products novel to microglia were neuromodulin (GAP43) and Flt3 ligand. Yet, treatment with TNF-α and IFN-γ led to widely different response profiles among the different cultures. Conclusion: These data show a surprising level of heterogeneity among human adult microglia cultures in their response to a pro-inflammatory stimulus despite the standardized methodology to examine this response.

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          Reactive microgliosis.

          Wolfgang J Streit, Sharon Walter, Nathan A. Pennell (1999)
          Damage to the central nervous system (CNS) elicits the activation of both astrocytes and microglia. This review is focused on the principal features that characterize the activation of microglia after CNS injury. It provides a critical discussion of concepts regarding microglial biology that include the relationship between microglia and macrophages, as well as the role of microglia as immunocompetent cells of the CNS. Mechanistic and functional aspects of microgliosis are discussed primarily in the context of microglial neuronal interactions. The controversial issue of whether reactive microgliosis is a beneficial or a harmful process is addressed, and a resolution of this dilemma is offered by suggesting different interpretations of the term 'activated microglia' depending on its usage during in vivo or in vitro experimentation.
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            Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo.

            W F Hickey, H. Kimura (1988)
            A crucial question in the study of immunological reactions in the central nervous system (CNS) concerns the identity of the parenchymal cells that function as the antigen-presenting cells in that organ. Rat bone marrow chimeras and encephalitogenic, major histocompatability--restricted T-helper lymphocytes were used to show that a subset of endogenous CNS cells, commonly termed "perivascular microglial cells," is bone marrow-derived. In addition, these perivascular cells are fully competent to present antigen to lymphocytes in an appropriately restricted manner. These findings are important for bone marrow transplantation and for neuroimmunological diseases such as multiple sclerosis.
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              Heterogeneous expression of the triggering receptor expressed on myeloid cells-2 on adult murine microglia.

              P Danielson, M. J. Cooper, Karl W Hasel … (2002)
              Microglial activation is an early and common feature of almost all neuropathologies, including multiple sclerosis, Alzheimer's disease and mechanical injury. To better understand the relative contributions microglia make toward neurodegeneration and neuroprotection, we used TOGA(R) to identify molecules expressed by microglia and regulated by inflammatory signals. Triggering receptor expressed on myeloid cells-2 (TREM-2) was among the mRNAs identified as being expressed by unactivated microglia, but down-regulated by lipopolysaccharide/interferon gamma. In the healthy CNS, not all microglia expressed TREM-2. Microglial expression of TREM-2 varied not only between brain regions but also within each brain region. Brain regions with an incomplete blood-brain barrier had the lowest percentages of TREM-2- expressing microglia, whereas the lateral entorhinal and cingulate cortex had the highest percentages. A novel form of TREM-2b that lacked a transmembrane domain was detected, perhaps indicating a soluble form of the protein. Taken together, these data suggest that (1) subsets of microglia are specialized to respond to defined extracellular signals; and (2) regional variations in TREM-2 expression may contribute to the varying sensitivities of different brain regions to similar pathological signals.
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                Author and article information

                Journal
                Journal ID (publisher-id): NIM
                Journal ID (nlm-ta): Neuroimmunomodulation
                Journal ID (doi): 10.1159/issn.1021-7401
                Title: Neuroimmunomodulation
                Publisher: S. Karger AG
                ISSN (Print): 1021-7401
                ISSN (Electronic): 1423-0216
                Publication date Subscription-year: 2005
                Publication date (Print): June 2005
                Publication date (Electronic): 27 June 2005
                Volume: 12
                Issue: 4
                Pages: 235-245
                Affiliations
                aDivision Biomedical Research, TNO Prevention and Health, Leiden, and bNetherlands Brain Bank, Amsterdam, The Netherlands
                Article
                Publisher ID: 85655 Other ID: Neuroimmunomodulation 2005;12:235–245
                DOI: 10.1159/000085655
                PubMed ID: 15990454
                SO-VID: 368b245c-8dfa-4b31-9e8f-b88a79c02e35
                Copyright © © 2005 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 12 January 2004
                Date accepted : 22 February 2005
                Page count
                Figures: 1, Tables: 6, References: 73, Pages: 11
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Keywords: Chemokines,Cytokines,Microglia,Gene expression profiling,Growth factor
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes, Neurology, Nutrition & Dietetics, Sexual medicine, Internal medicine, Pharmacology & Pharmaceutical medicine
                Keywords: Chemokines, Cytokines, Microglia, Gene expression profiling, Growth factor

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