DOCSLIB.ORG

Review Fibrocytes: a Unique Cell Population Implicated in Wound Healing

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read 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]). Fibroblasts found at sites of tissue injury flammation, infection, and metabolic deficiencies result may originate from different sources depending on the in the physical disruption of the normal cellular architec- wound/injury type. For example, in minor wounds fi- ture of the tissue. In response to tissue injury, the host broblasts may migrate from surrounding undamaged tis- commences a repair process that is regulated by cellular, sue, whereas fibrocytes may be recruited to deep tissue humoral and connective tissue mediators. The cell types wounds where they differentiate into fibroblasts. implicated in the repair of tissue injury include plate- The investigations by Bucala and colleagues in the early lets, monocytes/macrophages, T lymphocytes, endothe- 1990s that led to the discovery of ‘fibrocytes’ were based lial cells and connective tissue fibroblasts. Connective on the hypothesis that specialized ‘fibroblast-like cells’ tissue fibroblasts found at the sites of tissue injury and in present in experimentally implanted wound chambers areas of tissue remodeling are believed to play an essen- originated from the circulation. This discovery led to the tial role in the healing process. Although it is unclear identification and initial characterization of a distinct whether these connective tissue fibroblasts found in population of blood-borne CD34+/Col I+ fibroblast-like cells that rapidly enter sites of tissue injury [2]. Termed * Corresponding author. fibrocytes, these cells comprise ~0.1–0.5% of nonery- CMLS, Cell. Mol. Life Sci. Vol. 60, 2003 Review Article 1343 throcytic cells in the peripheral blood (as determined by Table 1. Fibrocyte-associated surface markers. spot immunofluorescence staining using anti-CD34-rho- Marker type Reference damine and anti-col I-fluorescein 5 (6)-isothiocyanate (FITC) of blood cells following erythrocyte lysis) [2]. Fi- ECM markers brocytes can be isolated from buffy coats prepared from Collagen I (2–8)] blood and cultured ex vivo [2–4]. These crude fibrocyte Collagen III [2] Fibronectin [2] preparations obtained from human or mouse blood are Vimentin [2] grown in Dulbecco’s modified Eagle medium containing CD markers fetal calf serum, without the addition of other growth fac- CD11a (LFA-1) [2–3] tors. After 10–14 days of incubation, ex vivo cultured fi- CD11b (Mac 1) [2] brocytes display an adherent, spindle-shaped morphol- CD13 (pan myeloid antigen) [2] CD34 (hemopoetic stem cell antigen) [2] ogy. Fibrocytes are then purified from this crude prepara- CD45 (leukocyte common antigen) [2] tion (70–80% pure) following negative selection for CD54 (ICAM) [2] other immune cell types (B cells, T cells and monocytes) CD58 (LFA-3) [2] (see fig. 1). The resulting fibrocyte population (>95% pure CD80 (B7-1) [3] CD86 (B7-2) [2–3] based on collagen I and CD11b staining, or collagen I and + MHC-related markers CD34 staining) has been characterized based on expres- MHC class II [2–3] sion of (i) extracellular surface markers [including cluster HLA-DP [3] of differentiation (CD) antigens, major histocompatibility HLA-DQ [3] complex (MHC)-like molecules and extracellular matrix HLA-DR [3] protein markers] (table 1) and (ii) cytokine, chemokine and Chemokine receptors (ligands) CCR3 (MCP-3, MCP-5, RANTES, MIP1a, HCC-1) [4] growth factor expression patterns (table 2). CCR5 (MIP1a, MIP1b, RANTES) [4] Fibrocytes are a unique CD45+ cell population [2] They CCR7 (ELC, SLC) [4] are distinct from monocytes, (CD14–, esterase–, CD54–), CXCR4, fusin (SDF-1) [4] dendritic cells (CD10–, CD25–, CD38–), Langerhans cells (CD1a–), T lymphocytes (CD3–, TCR–, CD4–, CD25–), B cells (CD19–), fibroblasts (collagen I+, CD34+), epithe- Table2.Fibrocytes secrete chemokines, cytokines and growth fac- – – lial cells (cytokeratin ) and endothelial cells (vWF , tors implicated in wound repair. CD11b+). In addition, when examined by electron mi- croscopy, fibrocytes exhibit unique cytoplasmic exten- Factor Comments Ref. sions intermediate in size between microvilli and a chemokines pseudopodia which further differentiate fibrocytes from MIP1a constitutive; ≠ with TGF-b1 or IL-1b [8] blood-borne leukocytes [2]. MIP1b constitutive; ≠ with TGF-b1 or IL-1b [8] Fibrocytes expressing CD34, CD11b and collagen I (but MCP-1 constitutive; ≠ with TGF-b1 or IL-1b [8] not CD14, CD3 or CD10) found in the peripheral blood, b chemokines wound sites and areas of tissue remodeling should not be IL-8 constitutive; ≠ with TGF-b1 or IL-1b [8, 31] GROa constitutive; ≠ with TGF-b1 or IL-1b [8] confused with fibrocytes or fibroblast cultures which are Cytokines TNF-a with IL-1b stimulation [8] IL-6 with IL-1b or TNF stimulation [8] IL-10 with IL-1b or TNF stimulation [8] Obtain whole blood Growth Factors Angiogenin constitutive [31] Centrifugation over Ficoll-Paque CTGF constitutive [31] IGF-1 constitutive [31] M-CSF constitutive [8, 31] Isolate buffy coat, wash and perform low speed spin (remove platelets) PDGF constitutive [31] TGFb constitutive [8] Plate resultant PBMCs in DMEM 10% FBS Other MMP-9 Constitutive, active and latent [31] aSMA ≠ with TGF-b1 [4] Culture for 10–14 days (‘crude fibrocytes’) Immunomagnetic bead separation to isolate ‘fibrocytes’ Fibrocytes (CD 14–/CD11b+/collagen I+ or CD14–/CD34+/collagen I+) Figure 1. Schematic representation indicating the isolation and growth conditions for peripheral blood fibrocytes. Taken from [4]. 1344 C. N. Metz The role of fibrocytes in wound healing implicated in the amyloid fibrillogenesis described by that cultured peripheral blood fibrocytes require interac- Harris and colleagues [5]. Nor should they be confused tion with activated T cells to permit their early differenti- with ‘spiral ligament fibrocytes’ located within the ear. ation. The requirement for T cell interaction is similar to Spiral ligament fibrocytes are the cells which intercon- that reported for the differentiation of CD1a+ dendritic nect with basal cells of the stria vascularis via gap junc- cells [9]. Following their interaction with T cells, it is pro- tions and are postulated to play a critical role in main- posed that they migrate to the wound site (see fig. 2 and taining cochlear homeostasis [6–7]. Both of these cell below). Within the wound, these early-differentiated fi- types appear to be unrelated to the blood-borne fibrocytes brocytes might further interact with recruited T cells and implicated in wound healing. then fully differentiate into mature fibrocytes following exposure to transforming growth factor-b (TGFb, ex- pressed in early wounds). In response to TGF-b, it is pos- Ex vivo cultured peripheral fibrocytes originate from tulated that these mature fibrocytes express increased a CD14+ cells and differentiate into a cell population smooth muscle actin (aSMA) which provides a contrac- with wound-healing potential tile force for wound closure and produce collagen and other critical extracellular matrix molecules that promote The precise origin of peripheral blood fibrocytes has puz- wound healing (fig. 2). zled investigators since their discovery. Fibrocytes ex- press CD45 (leukocyte common antigen), a marker of bone marrow-derived cells (see table 1). Early studies us- Where are fibrocytes found? ing sex-mismatched, bone marrow chimeric mice to- gether with DNA amplification of the male-specific SRY Although initially identified as a blood-borne cell popu- gene showed that circulating fibrocytes in vivo arise from lation (CD34+, CD11b+ and/or collagen1+), fibrocytes radioresistant bone marrow progenitor cells or an uniden- have been localized
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]
  • 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.
    [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]