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      Detection of Alveolar Fibrocytes in Idiopathic Pulmonary Fibrosis and Systemic Sclerosis

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          Abstract

          Background

          Fibrocytes are circulating precursors for fibroblasts. Blood fibrocytes are increased in patients with idiopathic pulmonary fibrosis (IPF). The aim of this study was to determine whether alveolar fibrocytes are detected in broncho-alveolar lavage (BAL), to identify their prognostic value, and their potential association with culture of fibroblasts from BAL.

          Methods

          We quantified fibrocytes in BAL from 26 patients with IPF, 9 patients with Systemic Sclerosis(SSc)-interstitial lung disease (ILD), and 11 controls. BAL cells were cultured to isolate alveolar fibroblasts.

          Results

          Fibrocytes were detected in BAL in 14/26 IPF (54%) and 5/9 SSc patients (55%), and never in controls. Fibrocytes were in median 2.5% [0.4–19.7] and 3.0% [2.7–3.7] of BAL cells in IPF and SSc-ILD patients respectively. In IPF patients, the number of alveolar fibrocytes was correlated with the number of alveolar macrophages and was associated with a less severe disease but not with a better outcome. Fibroblasts were cultured from BAL in 12/26 IPF (46%), 5/9 SSc-ILD (65%) and never in controls. The detection of BAL fibrocytes did not predict a positive culture of fibroblasts.

          Conclusion

          Fibrocytes were detected in BAL fluid in about half of the patients with IPF and SSc-ILD. Their number was associated with less severe disease in IPF patients and did not associate with the capacity to grow fibroblasts from BAL fluid.

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          Most cited references22

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          Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee.

          (1980)
          A multicenter, ongoing study of early-diagnosed cases of systemic sclerosis and comparison patients with systemic lupus erythematosus, polymyositis/dermatomyositis, and Raynaud's phenomenon was conducted in order to develop classification criteria for systemic sclerosis. Preliminary criteria are proposed namely, the finding of either the sole major criterion, i.e., proximal scleroderma, or two or more of the minor criteria, i.e., 1) sclerodactyly, 2) digital pitting scars of fingertips or loss of substance of the distal finger pad, and 3) bilateral basilar pulmonary fibrosis. When applied to the case and comparison patients included in this study, these proposed criteria had a 97% sensitivity for definite systemic sclerosis and 98% specificity.
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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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              Fibrocytes: emerging effector cells in chronic inflammation.

              Fibrocytes are mesenchymal cells that arise from monocyte precursors. They are present in injured organs and have both the inflammatory features of macrophages and the tissue remodelling properties of fibroblasts. Chronic inflammatory stimuli mediate the differentiation, trafficking and accumulation of these cells in fibrosing conditions associated with autoimmunity, cardiovascular disease and asthma. This Opinion article discusses the immunological mediators controlling fibrocyte differentiation and recruitment, describes the association of fibrocytes with chronic inflammatory diseases and compares the potential roles of fibrocytes in these disorders with those of macrophages and fibroblasts. It is hoped that this information prompts new opportunities for the study of these unique cells.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                16 January 2013
                : 8
                : 1
                : e53736
                Affiliations
                [1 ]Assistance Publique-Hopitaux de Paris, Service de Pneumologie A, Centre de Compétences Maladies Rares Pulmonaires, Hôpital Bichat, Paris, France
                [2 ]INSERM, Unité 700, Faculté Bichat, Université Paris 7, Paris, France
                [3 ]Assistance Publique-Hopitaux de Paris, Service d’Anesthésie et de Réanimation Chirurgicale, Hôpital Tenon, Paris, France
                [4 ]Assistance Publique-Hopitaux de Paris, Service de Radiologie, Hôpital Bichat, Paris, France
                [5 ]Assistance Publique-Hopitaux de Paris, Service de Médecine Interne, Hôpital Saint Antoine, Paris, France
                [6 ]Assistance Publique-Hopitaux de Paris, Service d'Explorations Fonctionnelles, Hôpital Saint Antoine, Paris, France
                [7 ]Université Paris Diderot Paris 7, PRES Sorbonne Paris Cité, Paris, France
                [8 ]Assistance Publique-Hopitaux de Paris, Service d'Anatomopathologie, Hôpital Bichat, Paris, France
                [9 ]Assistance Publique-Hopitaux de Paris, Service de Biochimie, Hôpital Bichat, Paris, France
                Helmholtz Zentrum München/Ludwig-Maximilians-University Munich, Germany
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: RB CQ KT PS MD BC. Performed the experiments: RB CQ SP JMS MB AF. Analyzed the data: RB CQ MPD KT PS MD BC. Contributed reagents/materials/analysis tools: RB CQ SP MPD KT PS MD BC. Wrote the paper: RB CQ MD BC.

                Article
                PONE-D-12-21571
                10.1371/journal.pone.0053736
                3547062
                23341987
                2ddedc98-9e7b-45f0-959f-24fd9ca5c75e
                Copyright @ 2013

                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
                : 12 July 2012
                : 4 December 2012
                Page count
                Pages: 8
                Funding
                This work was supported by a grant from the Association des Sclérodermiques de France (ASF), the Groupe Français de Recherche sur la Sclérodermie, the Chancellerie des Universités de Paris (legs Poix), the Fondation pour la Recherche Médicale, l'association Pierre Enjalran and the European Commission (FP7 grant agreement #202224, European IPF Network). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Respiratory System
                Respiratory Physiology
                Medicine
                Diagnostic Medicine
                Pathology
                Anatomical Pathology
                Cytopathology
                General Pathology
                Biomarkers
                Pulmonology
                Interstitial Lung Diseases
                Rheumatology

                Uncategorized
                Uncategorized

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