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      Gene Expression Study of Monocytes/Macrophages during Early Foreign Body Reaction and Identification of Potential Precursors of Myofibroblasts

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          Abstract

          Foreign body reaction (FBR), initiated by adherence of macrophages to biomaterials, is associated with several complications. Searching for mechanisms potentially useful to overcome these complications, we have established the signaling role of monocytes/macrophages in the development of FBR and the presence of CD34 + cells that potentially differentiate into myofibroblasts. Therefore, CD68 + cells were in vitro activated with fibrinogen and also purified from the FBR after 3 days of implantation in rats. Gene expression profiles showed a switch from monocytes and macrophages attracted by fibrinogen to activated macrophages and eventually wound-healing macrophages. The immature FBR also contained a subpopulation of CD34 + cells, which could be differentiated into myofibroblasts. This study showed that macrophages are the clear driving force of FBR, dependent on milieu, and myofibroblast deposition and differentiation.

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          Most cited references32

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          Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression.

          Comprehensive analysis of the gene expression profiles associated with human monocyte-to-macrophage differentiation and polarization toward M1 or M2 phenotypes led to the following main results: 1) M-CSF-driven monocyte-to-macrophage differentiation is associated with activation of cell cycle genes, substantiating the underestimated proliferation potential of monocytes. 2) M-CSF leads to expression of a substantial part of the M2 transcriptome, suggesting that under homeostatic conditions a default shift toward M2 occurs. 3) Modulation of genes involved in metabolic activities is a prominent feature of macrophage differentiation and polarization. 4) Lipid metabolism is a main category of modulated transcripts, with expected up-regulation of cyclo-oxygenase 2 in M1 cells and unexpected cyclo-oxygenase 1 up-regulation in M2 cells. 5) Each step is characterized by a different repertoire of G protein-coupled receptors, with five nucleotide receptors as novel M2-associated genes. 6) The chemokinome of polarized macrophages is profoundly diverse and new differentially expressed chemokines are reported. Thus, transcriptome profiling reveals novel molecules and signatures associated with human monocyte-to-macrophage differentiation and polarized activation which may represent candidate targets in pathophysiology.
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            WikiPathways: Pathway Editing for the People

            WikiPathways provides a collaborative platform for creating, updating, and sharing pathway diagrams and serves as an example of content curation by the biology community.
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              Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair.

              The host response to tissue injury requires a complex interplay of diverse cellular, humoral, and connective tissue elements. Fibroblasts participate in this process by proliferating within injured sites and contributing to scar formation and the longterm remodeling of damaged tissue. Fibroblasts present in areas of tissue injury generally have been regarded to arise by recruitment from surrounding connective tissue; however this may not be the only source of these cells. Long-term culture of adherent, human, and murine leukocyte subpopulations was combined with a variety of immunofluorescence and functional analyses to identify a blood-borne cell type with fibroblast-like properties. We describe for the first time a population of circulating cells with fibroblast properties that specifically enter sites of tissue injury. This novel cell type, termed a "fibrocyte," was characterized by its distinctive phenotype (collagen+/vimentin+/CD34+), by its rapid entry from blood into subcutaneously implanted wound chambers, and by its presence in connective tissue scars. Blood-borne fibrocytes contribute to scar formation and may play an important role both in normal wound repair and in pathological fibrotic responses.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2010
                23 September 2010
                : 5
                : 9
                : e12949
                Affiliations
                [1]Laboratory of Experimental Cardiac Surgery, Department of Cardiovascular Diseases, KULeuven, Leuven, Belgium
                Universidade do Porto, Portugal
                Author notes

                Conceived and designed the experiments: LM GDV IV WF. Performed the experiments: LM GDV IV AL. Analyzed the data: LM GDV IV AL WF. Contributed reagents/materials/analysis tools: LM GDV. Wrote the paper: LM GDV IV WF.

                Article
                10-PONE-RA-18507R1
                10.1371/journal.pone.0012949
                2944875
                20886081
                ef1978ee-e5e2-4e4c-bbbf-aa0477e9a1a1
                Mesure et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 30 April 2010
                : 16 August 2010
                Page count
                Pages: 10
                Categories
                Research Article
                Cell Biology/Cell Growth and Division
                Cell Biology/Leukocyte Signaling and Gene Expression
                Genetics and Genomics/Genetics of the Immune System
                Immunology/Genetics of the Immune System

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                Uncategorized

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