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      Circulating fibrocytes are involved in inflammation and leukocyte trafficking in neonates with necrotizing enterocolitis

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          Abstract

          Fibrocytes, ahematopoietic stem cell source of fibroblasts/myofibroblasts, were previously implicated to infiltrate into the intestinal and enhance inflammation.

          The aims of the present study were to elucidate the role of fibrocytes in necrotizing enterocolitis (NEC) pathogenesis and to explore the mechanisms by which fibrocytes contributed to the inflammatory responses.

          We investigated circulating and intestinal local fibrocytes from 32 patients with NEC, 8 patients with noninflammatory conditions of the gastrointestinal tract and 12 normal subjects.

          Significantly higher numbers of circulating fibrocytes were found in the peripheral blood from NEC patients than the controls ( P < .01). Numerous fibrocytes were found infiltrating the NEC intestinal mucous membranes. The percentage of fibrocytes to total leukocytes in the NEC inflammatory lesions was significantly increased compared with the percentage in the noninflammatory gastrointestinal tract. The fibrocyte attractant chemokine C-X-C motif chemokine ligand 12 (CXCL12) was significantly increased in the plasma and was detectable in 80% of the peritoneal lavage fluid from NEC patients but not the controls. Furthermore, chemokine expression was increased in fibrocytes infiltrating and trafficking to leukocyte sites. In culture, lipopolysaccharide (LPS) induced a significant increase in the expression of the Toll-like receptor (TLR4) signal, with the upregulation of p38 in both the isolated fibrocytes and macrophages. Similarly, interleukin (IL)-1β induced increased the upregulation of the IL-6, tumor necrosis factor (TNF)-α, and intercellular cell adhesion molecule-1 mRNAs but downregulated ColI in fibrocytes isolated from NEC patients compared with the controls.

          These findings indicate that circulating fibrocytes are increased in NEC patients and may be recruited to the inflammatory intestinal track, most likely through the CXCR4/CXCL12 axis. These cells may contribute to intestinal inflammation through TLR4 signaling by producing the TNF-α and IL-6 cytokines.

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          Peripheral blood fibrocytes: differentiation pathway and migration to wound sites.

          Fibrocytes are a distinct population of blood-borne cells that display a unique cell surface phenotype (collagen I+/CD11b+/CD13+/CD34+/CD45RO+/MHC class II+/CD86+) and exhibit potent immunostimulatory activities. Circulating fibrocytes rapidly enter sites of tissue injury, suggesting an important role for these cells in wound repair. However, the regulatory processes that govern the differentiation of blood-borne fibrocytes and the mechanisms that underlie the migration of these cells to wound sites are currently not known. We report herein that ex vivo cultured fibrocytes can differentiate from a CD14+-enriched mononuclear cell population and that this process requires contact with T cells. Furthermore, we demonstrate that TGF-beta1 (1-10 ng/ml), an important fibrogenic and growth-regulating cytokine involved in wound healing, increases the differentiation and functional activity of cultured fibrocytes. Because fibrocytes home to sites of tissue injury, we examined the role of chemokine/chemokine receptor interactions in fibrocyte trafficking. We show that secondary lymphoid chemokine, a ligand of the CCR7 chemokine receptor, acts as a potent stimulus for fibrocyte chemotaxis in vitro and for the homing of injected fibrocytes to sites of cutaneous tissue injury in vivo. Finally, we demonstrate that differentiated, cultured fibrocytes express alpha smooth muscle actin and contract collagen gels in vitro, two characteristic features of wound-healing myofibroblasts. These data provide important insight into the control of fibrocyte differentiation and trafficking during tissue repair and significantly expand their potential role during wound healing.
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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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              Circulating fibrocytes are an indicator of poor prognosis in idiopathic pulmonary fibrosis.

              The clinical management of idiopathic pulmonary fibrosis (IPF) remains a major challenge due to lack of effective drug therapy or accurate indicators for disease progression. Fibrocytes are circulating mesenchymal cell progenitors that are involved in tissue repair and fibrosis. To test the hypothesis that assay of these cells may provide a biomarker for activity and progression of IPF. Fibrocytes were defined as cells positive for CD45 and collagen-1 by flow cytometry and quantified in patients with stable IPF and during acute exacerbation of the disease. We investigated the clinical and prognostic value of fibrocyte counts by comparison with standard clinical parameters and survival. We used healthy age-matched volunteers and patients with acute respiratory distress syndrome as control subjects. Fibrocytes were significantly elevated in patients with stable IPF (n = 51), with a further increase during acute disease exacerbation (n = 7; P < 0.001 vs. control subjects). Patients with acute respiratory distress syndrome (n = 10) were not different from healthy control subjects or stable patients with IPF. Fibrocyte numbers were not correlated with lung function or radiologic severity scores, but they were an independent predictor of early mortality. The mean survival of patients with fibrocytes higher than 5% of total blood leukocytes was 7.5 months compared with 27 months for patients with less than 5% (P < 0.0001). Fibrocytes are an indicator for disease activity of IPF and might be useful as a clinical marker for disease progression. This study suggests that quantification of circulating fibrocytes may allow prediction of early mortality in patients with IPF.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                June 2017
                30 June 2017
                : 96
                : 26
                : e7400
                Affiliations
                [a ]Department of Neonatal, Children's Hospital, Chongqing Medical University, Chongqing
                [b ]Department of Pathology, Linyi People's Hospital, Linyi, Shandong Province
                [c ]Department of Pediatric General Surgery
                [d ]Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital, Chongqing Medical University
                [e ]Department of Neonatology, Yongchuan Hospital, Chongqing Medical University, Chongqing, P.R. China.
                Author notes
                []Correspondence: Yan Wang, Department of Neonatology, Yongchuan Hospital, Chongqing Medical University, Chongqing 400014, P.R. China (e-mail: 1102582077@ 123456qq.com ); Chunbao Guo, Department of Pediatric General Surgery, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Rd. Chongqing 400014, P.R. China (e-mails: guochunbao@ 123456cqmu.edu.cn & guochunbao@ 123456foxmail.com ).
                Article
                MD-D-17-01945 07400
                10.1097/MD.0000000000007400
                5500098
                28658176
                a78a7712-a45e-4a78-860d-cd81d25f677b
                Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

                History
                : 30 March 2017
                : 6 June 2017
                : 7 June 2017
                Categories
                3600
                Research Article
                Observational Study
                Custom metadata
                TRUE

                circulating fibrocytes,necrotizing enterocolitis (nec),sdf-1/cxcl12,tlr4

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