DOCSLIB.ORG

Fibrocytes and Fibroblasts—Where Are We

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Fibrocytes and Fibroblasts—Where Are We International Journal of Biochemistry and Cell Biology 116 (2019) 105595 Contents lists available at ScienceDirect International Journal of Biochemistry and Cell Biology journal homepage: www.elsevier.com/locate/biocel Fibrocytes and fibroblasts—Where are we now T ⁎ Sy Giin Chonga,b, Seidai Satoa,c, Martin Kolba, Jack Gauldiea, a Departments of Medicine and Pathology and Molecular Medicine, Firestone Institute for Respiratory Health, St Joseph’s Healthcare Hamilton, McMaster University, Hamilton, ON, Canada b School of Medicine and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland c Division of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan ARTICLE INFO ABSTRACT Keywords: Fibroblasts are considered major contributors to the process of fibrogenesis and the progression of matrix de- Fibrosis position and tissue distortion in fibrotic diseases such as Pulmonary Fibrosis. Recent discovery of the fibrocyte, a Fibroblast circulating possible precursor cell to the tissue fibroblast in fibrosis, has raised issues regarding the character- Fibrocyte ization of fibrocytes with respect to their morphology, growth characteristics in vitro, their biological role in vivo Myofibroblast and their potential utility as a biomarker and/ or treatment target in various human diseases. Characterization Extracellular matrix studies of the fibrocyte continue as does emerging conflicting data concerning the relationship to orwiththe Pulmonary fibrosis Exosomes lung fibroblast. The source of signals that direct the traffic of these cells, as well as their response totherapeutic Cancer-associated fibroblast intervention with newly available drugs, bring new insights to the understanding of this cell type. The identi- fication of exosomes from fibrocytes that can affect resident fibroblast activities suggest mechanisms oftheir influence on pathogenesis. Moreover, interesting comparisons with other pathologies are emerging involving the influence of circulating mesenchymal precursor cells on tissue responses. 1. Introduction express markers of both haematopoietic cells (CD34, CD43, CD68, CD164, CD45, LSP-1, MHC class II) and stromal cells (Pilling et al., The description of fibrocytes in 1994 by Bucala et al. (1994) marks 2009). To differentiate between fibrocytes and fibroblasts, there areat the beginning of an expanding field of discovery about these fibroblast- least 6 commercial reagents available which allow detection of cellular like cells, derived from the bone marrow and identified as a circulating fibronectin, CD90, TE-7, CD 248, HA-BP and FAP(Pilling et al., 2009). mesenchymal cell precursor. Since this initial discovery, there have In addition, fibrocytes were demonstrated to assume an irregular star been an increasing number of studies done on the characterization of (stellate) or spindle-shaped (fusiform) cell form when adherent or fibrocytes with respect to their morphology, growth characteristics in having migrated to sites of tissue injury (Pilling et al., 2009; Quan and vitro, their biological role in vivo and their potential utility as a bio- Bucala, 2006; Quan et al., 2004). Consistent with the knowledge at that marker and/or treatment target in various human diseases including time, for several years, the identification of collagen production (con- asthma, fibrosis of lung, liver and kidney, along with systemic fibrosis tent), together with the surface expression of CD34 and/or CD45, were and atherosclerosis, to name a few. used as the minimum criteria for identifying fibrocytes in culture, in tissue sections or in the circulation. That criteria still applies to this day 2. Characteristics of fibrocytes as there is still no single marker found for fibrocytes and fibroblasts. Table 1 provides a guide on the common markers used for the identi- Fibrocytes, which originate from bone marrow, bear characteristics fication and differentiation of fibrocytes and fibroblasts. However, the of both fibroblasts and monocytes, and hence exhibit a combination of identification of fibrocytes in culture remains difficult, partly duetothe connective tissue cell and myeloid features (Herzog and Bucala, 2010). plasticity of the cells. Fibrocytes express the stem cell marker CD34, the pan-haematopoietic Fibrocytes possess the ability to differentiate along mesenchymal marker CD45, monocyte markers including CD14 and CD11 and pro- lineages, including commitment to myofibroblasts or to adipocyte cells duce components of the connective tissue matrix, such as collagen-I, under different environmental cues (Hong et al., 2007), a feature dis- collagen-III and vimentin (Herzog and Bucala, 2010). Mature fibrocytes tinguishing them from fibroblasts. Fibrocytes demonstrate the ⁎ Corresponding author at: Departments of Medicine and Pathology and Molecular Medicine, Firestone Institute for Respiratory Health, St Joseph’s Healthcare Hamilton, McMaster University, Hamilton, ON, Canada. E-mail address: [email protected] (J. Gauldie). https://doi.org/10.1016/j.biocel.2019.105595 Received 8 July 2019; Received in revised form 26 August 2019; Accepted 28 August 2019 Available online 29 August 2019 1357-2725/ © 2019 Published by Elsevier Ltd. S.G. Chong, et al. International Journal of Biochemistry and Cell Biology 116 (2019) 105595 Table 1 well as for CCR7, expressed on fibrocytes, has been found to be high in Common markers used for the identification of fibrocytes and fibroblasts. the lungs and blood of patients with IPF and these levels correlate with Pilling et al. (2009) provide a more extensive list of markers present on fi- the numbers of circulating fibrocytes (Mehrad et al., 2007). The num- brocytes and fibrobroblasts. bers also correlate with the number of lung fibrocytes seen in IPF pa- Markers Fibrocytes Fibroblasts tients. Interestingly, in this study, they found that lung fibrocytes in IPF patients possess different characteristics compared to circulating fi- CD11a Present Absent brocytes (Heukels et al., 2018). This finding could be significant and CD134 Present Present CD45 Present Absent requires further investigation in detail if therapeutic targets in fibrotic CXCR4 Present Absent lung diseases are desired. The differential characteristics of circulating Alpha smooth muscle actin Present Present and lung fibrocytes could provide a reason for the ineffectiveness of Col-1 Present Present pirfenidone or nintedanib as a therapeutic cure for IPF patients, despite CD90 Absent Present their proven capability to slow down disease progression. TE-7 Absent Present S100A8/A9 Present Absent Also important to note, there are other chemokine ligand-receptor Fibronectin Absent Present pathways of fibrocyte recruitment, which includes chemokine sec- Vimentin Present Present ondary lymphoid tissue chemokine/chemokine ligand 21-CCR7 as well FAP Absent Present as CCL2-CCR2 and CCL12 (MCP5)-CCR2 (Phillips et al., 2004; Heukels et al., 2018; Gurczynski et al., 2016; Ekert et al., 2011). The existence of multiple recruitment pathways raises the question as to which pathway expression of CD34, CD45, collagen and vimentin during the early is activated under which environmental condition and what influences phase of their departure from the bone marrow or during the early fibrocytes to take one pathway over the others. This has not yetbeen phase of culture (Gomperts and Strieter, 2007). However, they lose fully delineated. expression of CD34 and CD45 and increasingly gain expression of alpha As there are two approved drugs currently in use for the treatment smooth-muscle actin (α-SMA) to become myofibroblast-like cells under of pulmonary fibrosis (nintedanib and pirfenidone), studies have been the influence of factors, such as transforming growth factor β (TGFβ) initiated to determine whether the fibrocyte population is affected by (Kage and Borok, 2012) and endothelin. Fibrocytes were also shown to these drugs. Inomata et al examined the effect of pirfenidone treatment differentiate to adipocytes when exposed to adipogenic induction on accumulation of lung fibrocytes in a murine osmotic pump 7day media and are also suggested to differentiate to chondrocytes and os- infusion bleomycin-induced pulmonary fibrosis model. In their study, teoblasts when cultured under appropriate conditions (Gomperts and they confirmed that the accumulation of fibrocytes in murine fibrotic Strieter, 2007). Therefore, it is not surprising to note that fibrocytes lungs was reduced by treatment with pirfenidone through the inhibition have been implicated in the pathogenesis of multiple diseases and such of production of CCL2 and CCL12 and also through the partial inhibi- plasticity could be a reason why it is difficult to treat certain diseases, tion of production of CXCL12 (Inomata et al., 2014). Moreover, they such as idiopathic pulmonary fibrosis (IPF). Our understanding of this also found that inhibition of fibrocyte accumulation in the lungs was plasticity feature of fibrocytes remains poor despite significant re- significant on day 14 after bleomycin administration. However, the search. effect of pirfenidone on fibrocyte accumulation on day 21 wasless Philips et al demonstrated the importance of CXCR4-SDF-1/CXCL12 significant (Inomata et al., 2014). It is worth noting in this osmotic chemokine pathways in recruiting fibrocytes from bone marrow to the pump model, with a more chronic administration of bleomycin, marked target tissue (Phillips et al., 2004). Mice with
Load more

Recommended publications
  • Vocabulario De Morfoloxía, Anatomía E Citoloxía Veterinaria
    Vocabulario de Morfoloxía, anatomía e citoloxía veterinaria (galego-español-inglés) Servizo de Normalización Lingüística Universidade de Santiago de Compostela COLECCIÓN VOCABULARIOS TEMÁTICOS N.º 4 SERVIZO DE NORMALIZACIÓN LINGÜÍSTICA Vocabulario de Morfoloxía, anatomía e citoloxía veterinaria (galego-español-inglés) 2008 UNIVERSIDADE DE SANTIAGO DE COMPOSTELA VOCABULARIO de morfoloxía, anatomía e citoloxía veterinaria : (galego-español- inglés) / coordinador Xusto A. Rodríguez Río, Servizo de Normalización Lingüística ; autores Matilde Lombardero Fernández ... [et al.]. – Santiago de Compostela : Universidade de Santiago de Compostela, Servizo de Publicacións e Intercambio Científico, 2008. – 369 p. ; 21 cm. – (Vocabularios temáticos ; 4). - D.L. C 2458-2008. – ISBN 978-84-9887-018-3 1.Medicina �������������������������������������������������������������������������veterinaria-Diccionarios�������������������������������������������������. 2.Galego (Lingua)-Glosarios, vocabularios, etc. políglotas. I.Lombardero Fernández, Matilde. II.Rodríguez Rio, Xusto A. coord. III. Universidade de Santiago de Compostela. Servizo de Normalización Lingüística, coord. IV.Universidade de Santiago de Compostela. Servizo de Publicacións e Intercambio Científico, ed. V.Serie. 591.4(038)=699=60=20 Coordinador Xusto A. Rodríguez Río (Área de Terminoloxía. Servizo de Normalización Lingüística. Universidade de Santiago de Compostela) Autoras/res Matilde Lombardero Fernández (doutora en Veterinaria e profesora do Departamento de Anatomía e Produción Animal.
    [Show full text]
  • An Histologie and Immunohistochemical Study
    Bull Group Int Rech Sci Stomatol et Odontol - Vol 34 n° 3-4, 1991 The connective tissue cells of human dental pulp: An histologie and immunohistochemical study LYN Peifen*, FIORE-DONNO G.** and LOMBARD1 T.** * Department ofStomatology, Tbird Hospital ofBeijing Medical University, China. ** Division of Stomatology School ofDental Medicine, Faculty ofMedicine Geneva, Switzerland. SUMMARY Twenty human healthy teeth were extracted for orthondontic purposes and processed for histological, and immunohistochemical examination. Odontoblasts were pseudostratified in depth of 1-8 cells in pulpward direction showing the zone of Weil and the cell-rich zone in coronal third pulp. In the central part of pulp tissue, fibroblasts were arranged as a network. These cells strongly immunoreacted with an antibody (monoclonal and polyclonal) directed against the intermediate filament vimentin. The product reaction was specifically located in the cytoplasm. Near vessels occasional lymphocytes and mast cells were also pré¬ sent. Collagen fibers formed a plexus below the cell-rich zone in middle and coronal pulp. KEY WORDS: Pulp - Fibroblast - Man - Histology - Immunohistochemistry. RESUME Vingt dents humaines saines ont été avulsées pour des raisons orthodontiques et traitées pour être exami¬ nées du point de vue histologique et par immunohistochimie. Les odontoblastes étaient pseudostratifiés (1-8 cellules) et dans le tiers coronaire de la pulpe soit la zone de Weil une zone riche en cellules est pré¬ sente. Dans la partie centrale de la pulpe, les fibroblastes forment un réseau. Ces cellules sont fortement immuno-marquées par un anticorps (monoclonal ou polyclonal) dirigé contre la vimentine. Le marquage est spécifiquement localisé dans le cytoplasme. A proximité des vaisseaux, des mastocytes ainsi que des lymphocytes sont présents.
    [Show full text]
  • Effect of Norbixin-Based Poly(Hydroxybutyrate) Membranes on the Tendon Repair Process After Tenotomy in Rats1
    ACTA CIRÚRGICA BRASILEIRA ORIGINAL ARTICLE Experimental Surgery Effect of norbixin-based poly(hydroxybutyrate) membranes on the tendon repair process after tenotomy in rats1 Lízia Daniela e Silva NascimentoI , Renata Amadei NicolauII , Antônio Luiz Martins Maia FilhoIII , José Zilton Lima Verde SantosIV , Khetyma Moreira FonsecaV , Danniel Cabral Leão FerreiraVI , Rayssilane Cardoso de SousaVII , Vicente Galber Freitas VianaVIII , Luiz Fernando Meneses CarvalhoIX , José Figueredo-SilvaX I Fellow PhD degree, Postgraduate Program in Biomedical Engineering, Universidade do Vale do Paraíba (UNIVAP), Sao Jose dos Campos-SP. Assistant Professor of Kinesiology, MSc, Health Sciences Center, Physical Therapy, Universidade Estadual do Piauí (UESPI), Teresina-PI, Brazil. Conception, design, intellectual and scientific content of the study; acquisition and interpretation of data; technical procedures; manuscript preparation. II PhD, Collaborator, Postgraduate Program in Biomedical Engineering of the Research and Development Institute, UNIVAP, Sao Jose dos Campos-SP, Brazil. Conception, design, intellectual and scientific content of the study; interpretation of data; critical revision. III Associate Professor of Physiology, Health Sciences Center, UESPI, Teresina-PI, Brazil. Technical procedures. IV MSc, Assistant Professor, Center of Health Sciences, Medicine and Physical Therapy, UESPI, Teresina-PI. Brazil. Histopathological examinations. V Fellow PhD degree, Postgraduate Program in Pharmacology, Universidade Federal do Ceará (UFC), Fortaleza-CE.
    [Show full text]
  • TNF-Α–Stimulated Fibroblasts Secrete Lumican to Promote Fibrocyte Differentiation
    TNF-α–stimulated fibroblasts secrete lumican to promote fibrocyte differentiation Darrell Pillinga,1, Varsha Vakilb, Nehemiah Coxa, and Richard H. Gomera,b,1 aDepartment of Biology, Texas A&M University, College Station, TX 77843; and bDepartment of Biochemistry and Cell Biology, Rice University, Houston, TX 77005 Edited by Erica Herzog, Department of Medicine, Yale University, New Haven, CT, and accepted by the Editorial Board August 12, 2015 (received for review April 15, 2015) In healing wounds and fibrotic lesions, fibroblasts and monocyte- lumican levels in the lungs, suggesting that pulmonary fibrosis derived fibroblast-like cells called fibrocytes help to form scar may be in part due to elevated lumican levels. These data suggest tissue. Although fibrocytes promote collagen production by fibro- that lumican may be one of the unknown signals from fibroblasts blasts, little is known about signaling from fibroblasts to fibrocytes. In to fibrocytes that mediates part of a fibroblast-fibrocyte feedback this report, we show that fibroblasts stimulated with the fibrocyte- loop that potentiates fibrosis. secreted inflammatory signal tumor necrosis factor-α secrete the small leucine-rich proteoglycan lumican, and that lumican, but not Results the related proteoglycan decorin, promotes human fibrocyte differ- TNF-α–Stimulated Fibroblasts Promote Fibrocyte Differentiation. To entiation. Lumican competes with the serum fibrocyte differentiation test the hypothesis that activated fibroblasts might secrete soluble inhibitor serum amyloid P, but dominates over the fibroblast-secreted factors that promote fibrocyte differentiation, we added condi- fibrocyte inhibitor Slit2. Lumican acts directly on monocytes, and un- tioned medium from human fibroblasts incubated with TNF-α like other factors that affect fibrocyte differentiation, lumican has no (FCM+TNF-α) to human peripheral blood mononuclear cells detectable effect on macrophage differentiation or polarization.
    [Show full text]
  • Nomina Histologica Veterinaria, First Edition
    NOMINA HISTOLOGICA VETERINARIA Submitted by the International Committee on Veterinary Histological Nomenclature (ICVHN) to the World Association of Veterinary Anatomists Published on the website of the World Association of Veterinary Anatomists www.wava-amav.org 2017 CONTENTS Introduction i Principles of term construction in N.H.V. iii Cytologia – Cytology 1 Textus epithelialis – Epithelial tissue 10 Textus connectivus – Connective tissue 13 Sanguis et Lympha – Blood and Lymph 17 Textus muscularis – Muscle tissue 19 Textus nervosus – Nerve tissue 20 Splanchnologia – Viscera 23 Systema digestorium – Digestive system 24 Systema respiratorium – Respiratory system 32 Systema urinarium – Urinary system 35 Organa genitalia masculina – Male genital system 38 Organa genitalia feminina – Female genital system 42 Systema endocrinum – Endocrine system 45 Systema cardiovasculare et lymphaticum [Angiologia] – Cardiovascular and lymphatic system 47 Systema nervosum – Nervous system 52 Receptores sensorii et Organa sensuum – Sensory receptors and Sense organs 58 Integumentum – Integument 64 INTRODUCTION The preparations leading to the publication of the present first edition of the Nomina Histologica Veterinaria has a long history spanning more than 50 years. Under the auspices of the World Association of Veterinary Anatomists (W.A.V.A.), the International Committee on Veterinary Anatomical Nomenclature (I.C.V.A.N.) appointed in Giessen, 1965, a Subcommittee on Histology and Embryology which started a working relation with the Subcommittee on Histology of the former International Anatomical Nomenclature Committee. In Mexico City, 1971, this Subcommittee presented a document entitled Nomina Histologica Veterinaria: A Working Draft as a basis for the continued work of the newly-appointed Subcommittee on Histological Nomenclature. This resulted in the editing of the Nomina Histologica Veterinaria: A Working Draft II (Toulouse, 1974), followed by preparations for publication of a Nomina Histologica Veterinaria.
    [Show full text]
  • Tendon Healing with Allogenic Fibroblast and Static Magnetic Field in Rabbit Model
    IJVS 2015; 10(2); Serial No:23 IRANIAN JOURNAL OF VETERINARY SURGERY (IJVS) WWW.IVSA.IR Tendon Healing with Allogenic Fibroblast and Static Magnetic Field in Rabbit Model Amin Bigham-Sadegh*1, Setare Ghasemi 2, Iraj Karimi 3, Pezhman Mirshokraei 4, Hasan Nazari 5, Ahmad Oryan 6 Abstract Objectives- Tendons are integral parts of musculoskeletal system and are subjected to injury. Fibroblast is used in tendon healing, however, there is no proved and reported result regarding concurrent use of allogenic fibroblast with static magnetic field in tendon healing. In addition, there are some studies done on the effect of magnetic fields on tendon healing but the results are antithesis. The aim of this study is to evaluate the effect of simultaneous application of fibroblast and magnetic field on tendon healing in rabbit model. Design- Experimental study. Animals- Eighteen female rabbits, 15 months old and weighing 3.0±0.5 kg were used in this study. Procedures- Two legs of eighteen rabbits were divided into 6 groups. After skin incision, superficial flexor tendon was exposed and cut transversely and then sutured. In control group tendon injury were created in right and left legs and sutured in bunnell mayer suturing technique. In culture media substance group after tendon injury in two legs, 0.5 cc culture substance was injected in the injured tendon area in two legs. In fibroblast group, fibroblast cells were injected in the tendon injured area in both legs. Then all injuries legs were dressed up, a piece of magnet was placed in the surrounding bandage of the left leg for 7 days and right legs were left empty.
    [Show full text]
  • Histology and Histopathology from Cell Biology to Tissue Engineering
    I Histology and Histopathology From Cell Biology to Tissue Engineering Volume 32 (Supplement 1), 2017 http://www.hh.um.es SANTIAGO DE COMPOSTELA 5 - 8 Septiembre 2017 ! ! XIX Congreso de la Sociedad Española de Histología e Ingeniería Tisular IV Congreso Iberoamericano de Histología VII Internacional Congress of Histology and Tissue Engineering ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! Santiago de Compostela, 5 – 8 de Septiembre de 2017 Honorary President Andrés Beiras Iglesias Organizing Committee Presidents Tomás García-Caballero Rosalía Gallego *yPH] Scientific Committee Concepción Parrado Romero Ana Alonso Varona (UPV/EHU) Ana María Navarro Incio (Universidad de Oviedo) Antonia Álvarez Díaz (Universidad del País Vasco) Rosa Noguera Salvá (Universidad de Valencia) Rafael Álvarez Nogal (Universidad de León) Juan Ocampo López (Univ. Autónoma del Estado Rosa Álvarez Otero (Universidad de Vigo) de Hidalgo. México.) Miguel Ángel Arévalo Gómez (Universidad de Luis Miguel Pastor García (Universidad de Murcia) Salamanca) Juan Ángel Pedrosa Raya (Universidad de Jaén) Julia Buján Varela (Universidad de Alcalá) José Peña Amaro (Universidad de Córdoba) Juan José Calvo Martín (Universidad de la Carmen de la Paz Pérez Olvera (Universidad República, Uruguay) Autónoma de México.) Antonio Campos Muñoz (Universidad de Granada) Eloy Redondo García (Universidad de Extremadura) Pascual Vicente Crespo Ferrer (Universidad de Javier F. Regadera González (Universidad de Granada) Autónoma de Madrid) Juan Cuevas Álvarez (Universidad de Santiago) Viktor K Romero Díaz (Univ. Autónoma de Nuevo Joaquín De Juan Herrero (Universidad de Alicante) León. México.) María Rosa Fenoll Brunet (Universidad Rovira i Amparo Ruiz Saurí (Universidad de Valencia) Virgili) Francisco José Sáez Crespo (Universidad del País María Pilar Fernández Mateos (Universidad Vasco) Complutense de Madrid) Mercedes Salido Peracaula (Universidad de Cádiz) Benito Fraile Laiz (Universidad de Alcalá) Luis Santamaría Solís (Universidad Autónoma de Ricardo Fretes (Universidad Nacional de Córdoba.
    [Show full text]
  • Alcoholic Extract of Tarantula Cubensis Improves Sharp Ruptured Tendon Healing After Primary Repair in Rabbits
    An Original Study Alcoholic Extract of Tarantula Cubensis Improves Sharp Ruptured Tendon Healing After Primary Repair in Rabbits Ahmad Oryan, DVM, PhD, Ali Moshiri, DVM, DVSc, and Abdolhamid Meimandi Parizi, DVM, PhD tendons would be a concern for orthopedic surgeons. Abstract Sharp ruptured tendons heal slowly and often result This study was designed to investigate the effects of in formation of scar tissue or fibrous adhesion which tarantula cubensis (TC) on the superficial digital flexor increases the risk of reinjury at the repair site.2,4,5 tendon (SDFT) rupture after surgical anastomosis, on day Various techniques have been described that provide 84-postinjury (DPI) in rabbits. Forty white New Zealand, robust tendon anastomosis with minimal gap forma- mature, male rabbits were randomly and evenly divided tion, limited adhesion, and preservation of the ten- into treated and control groups. After tenotomy and pri- don’s intrinsic blood supply.2,3,6 However, after surgical mary repair, the injured legs were immobilized for 2 weeks. 2,7 TC was injected subcutaneously over the lesion on 3, reconstruction, the tendons do not properly heal and 7, and 10 DPI. The control animals received subcutane- therapeutic agents may have some values to stimulate 4 ous injections of normal saline similarly. Animal’s weight, tendon healing. tendon diameter, clinical status, radiographic and ultraso- Tarantula cubensis (TC) has been used in homeopa- nographic evaluations were recorded at weekly intervals. thy to treat mixed mammary tumors, pododermatitis,
    [Show full text]
  • Fibroblasts Secrete Slit2 to Inhibit Fibrocyte Differentiation and Fibrosis
    Fibroblasts secrete Slit2 to inhibit fibrocyte differentiation and fibrosis Darrell Pillinga,1, Zhichao Zhenga, Varsha Vakilb, and Richard H. Gomera,b,1 aDepartment of Biology, Texas A&M University, College Station, TX 77843; and bDepartment of Biochemistry and Cell Biology, Rice University, Houston, TX 77251 Edited by Richard Bucala, Yale University School of Medicine, New Haven, CT, and accepted by the Editorial Board November 18, 2014 (received for review September 10, 2014) Monocytes leave the blood and enter tissues. In healing wounds and needed. To test the hypothesis that fibroblasts might secrete fibrotic lesions, some of the monocytes differentiate into fibroblast- soluble factors to signal monocytes that have entered the tissue like cells called fibrocytes. In healthy tissues, even though monocytes to not differentiate into fibrocytes, we added conditioned me- enter the tissue, for unknown reasons, very few monocytes differ- dium from human fibroblasts (FCM) to human peripheral blood entiate into fibrocytes. In this report, we show that fibroblasts from mononuclear cells (PBMCs) in conditions where some of the healthy human tissues secrete the neuronal guidance protein Slit2 monocytes in the PBMCs would normally differentiate into and that Slit2 inhibits human fibrocyte differentiation. In mice, injec- fibrocytes. The PBMCs were cultured for 5 d in serum-free tions of Slit2 inhibit bleomycin-induced lung fibrosis. In lung tissue medium (SFM) with FCM from human adult skin, adult lung, from pulmonary fibrosis patients with relatively normal lung func- and MRC5 fetal lung fibroblasts. In the absence of fibroblast tion, Slit2 has a widespread distribution whereas, in patients with conditioned medium, we observed 520–1,660 fibrocytes per 105 advanced disease, there is less Slit2 in the fibrotic lesions.
    [Show full text]
  • 4, IL-13, and IL-17A Differentially Affect the Profibrotic and Proinflammatory Functions of Fibrocytes from Asthmatic Patients
    ARTICLES nature publishing group See COMMENTARY page XX Interleukin (IL)-4, IL-13, and IL-17A differentially affect the profibrotic and proinflammatory functions of fibrocytes from asthmatic patients A B e l l i n i 1 , M A M a r i n i 2 , L B i a n c h e t t i 1 , M B a r c z y k 1 , M S c h m i d t 1 a n d S M a t t o l i 1 Fibrocytes contribute to the fibrotic changes most frequently observed in forms of asthma where inflammation is driven by T helper type 2 (Th2) cells. The mechanisms that regulate the profibrotic function of asthmatic fibrocytes are largely unknown. We isolated circulating fibrocytes from patients with allergen-exacerbated asthma, who showed the presence of fibrocytes, together with elevated concentrations of interleukin (IL)-4 and IL-13 and slightly increased concentrations of the Th17 cell-derived IL-17A, in induced sputum. Fibrocytes stimulated with IL-4 and IL-13 produced high levels of collagenous and non-collagenous matrix components and low levels of proinflammatory cytokines. Conversely, fibrocytes stimulated with IL-17A proliferated and released proinflammatory factors that may promote neutrophil recruitment and airway hyperresponsiveness. IL-17A also indirectly increased -smooth muscle actin but not collagen expression in fibrocytes. Thus, fibrocytes may proliferate and express a predominant profibrotic or proinflammatory phenotype in asthmatic airways depending on the local concentrations of Th2- and Th17-derived cytokines. INTRODUCTION tion. 3,6,7,9,10 This thickening of the subepithelial reticular sheet
    [Show full text]
  • Aging Promotes Pro-Fibrotic Matrix Production and Increases Fibrocyte Recruitment During Acute Lung Injury
    Advances in Bioscience and Biotechnology, 2014, 5, 19-30 ABB http://dx.doi.org/10.4236/abb.2014.51004 Published Online January 2014 (http://www.scirp.org/journal/abb/) Aging promotes pro-fibrotic matrix production and increases fibrocyte recruitment during acute lung injury Viranuj Sueblinvong1*, Wendy A. Neveu1, David C. Neujahr1,2, Stephen T. Mills1, Mauricio Rojas3, Jesse Roman4, David M. Guidot1,5 1Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA, USA 2McKelvey Lung Transplantation Center, Emory University School of Medicine, Atlanta, GA, USA 3Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA 4Division of Pulmonary, Allergy and Critical Care Medicine, University of Louisville, Louisville, KY, USA 5Division of Pulmonary, Allergy and Critical Care Medicine, Atlanta VAMC, Decatur, GA, USA Email: *[email protected] Received 26 November 2013; revised 25 December 2013; accepted 5 January 2014 Copyright © 2014 Viranuj Sueblinvong et al. This is an open access article distributed under the Creative Commons Attribution Li- cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In accordance of the Creative Commons Attribution License all Copyrights © 2014 are reserved for SCIRP and the owner of the intel- lectual property Viranuj Sueblinvong et al. All Copyright © 2014 are guarded by law and by SCIRP as a guardian. ABSTRACT blasts induced apoptosis. These findings suggest that senescence increases fibrocyte recruitment to the lung Fibrotic lung diseases increase with age. Previously following injury and that loss of Thy-1 expression by we determined that senescence increases tissue ex- lung fibroblasts promotes fibrocyte retention and pression of fibronectin EDA (Fn-EDA) and decreases myofibroblast transdifferentiation that renders the fibroblast expression of Thy-1, and that fibrocytes “aging lung” susceptible to fibrosis.
    [Show full text]
  • Review Fibrocytes: a Unique Cell Population Implicated in Wound Healing
    CMLS, Cell. Mol. Life Sci. 60 (2003) 1342–1350 1420-682X/03/071342-09 DOI 10.1007/s00018-003-2328-0 CMLS Cellular and Molecular Life Sciences © Birkhäuser Verlag, Basel, 2003 Review Fibrocytes: a unique cell population implicated in wound healing C. N. Metz North Shore-LIJ Research Institute, 350 Community Drive, Manhasset, New York 11030 (USA), Fax: + 1 516 365 5090, e-mail: [email protected] Received 25 November 2002; received after revision 31 December 2002; accepted 16 January 2003 Abstract. Following tissue damage, host wound healing gin remains a mystery. A unique cell population, known ensues. This process requires an elaborate interplay be- as fibrocytes, has been identified and characterized. One tween numerous cell types which orchestrate a series of of the unique features of these blood-borne cells is their regulated and overlapping events. These events include ability to home to sites of tissue damage. This article re- the initiation of an antigen-specific host immune re- views the identification and characterization of fibro- sponse, blood vessel formation, as well as the production cytes, summarizes the potential role of fibrocytes in the of critical extracellular matrix molecules, cytokines and numerous steps of the wound-healing process and high- growth factors which mediate tissue repair and wound lights the potential role of fibrocytes in fibrotic disease closure. Connective tissue fibroblasts are considered es- pathogenesis. sential for successful wound healing; however, their ori- Key words. Tissue repair; fibrosis; tissue remodeling; TGFb; angiogenesis; antigen presentation. What are fibrocytes? wounds and scar tissues originate from the circulation or The discovery, isolation and initial characterization from the surrounding tissue areas, the concept that fi- of fibrocytes broblast-like cells found within the wound originate from the peripheral blood dates back almost 100 years (re- Wounds or tissue injuries caused by trauma, burns, in- viewed in [1]).
    [Show full text]