Hyaluronidase recruits mesenchymal-like cells to the lung and ameliorates fibrosis

Bitencourt, Pereira, Ramos, Sampaio, Arantes, Aronoff, Faccioli

Description

Hyaluronidases (HYALs) comprise a group of enzymes that degrade hyaluronic acid (HA). In this report, we reveal that a single intranasal inoculation of HYAL induces an increase in mononuclear cells within the bronchoalveolar space demonstrating a mesenchymal-like phenotype, expressing stem cell antigen-1 (SCA-1), CD44 and CD73 but not CD34, CD45, CD3, CD4, CD8 or CD19. This influx of mesenchymal stem cell (MSC)-like cells was dependent on leukotriene production within the lung parenchyma. These findings prompted experiments demonstrating that HYAL treatment potently blocked bleomycin-induced lung injury and fibrosis while decreasing transforming growth factor (TGF)-β production and collagen deposition. These data suggest that HYAL is a novel and promising tool to use autologous MSC-like cells in the treatment of pulmonary fibrosis.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 0
• Langue: English

Extrait

Bitencourt et al . Fibrogenesis & Tissue Repair 2011, 4 :3 http://www.fibrogenesis.com/content/4/1/3

R E S E A R C H Open Access Hyaluronidase recruits mesenchymal-like cells to the lung and ameliorates fibrosis Claudia S Bitencourt 1 , Priscilla AT Pereira 1 , Simone G Ramos 2 , Suely V Sampaio 1 , Eliane C Arantes 3 , David M Aronoff 4 , Lúcia H Faccioli 1*

Abstract Hyaluronidases (HYALs) comprise a group of enzymes that degrade hyaluronic acid (HA). In this report, we reveal that a single intranasal inoculation of HYAL induces an increase in mononuclear cells within the bronchoalveolar space demonstrating a mesenchymal-like phenotype, expressing stem cell antigen-1 (SCA-1), CD44 and CD73 but not CD34, CD45, CD3, CD4, CD8 or CD19. This influx of mesenchymal stem cell (MSC)-like cells was dependent on leukotriene production within the lung parenchyma. These findings prompted experiments demonstrating that HYAL treatment potently blocked bleomycin-induced lung injury and fibrosis while decreasing transforming growth factor (TGF)-b production and collagen deposition. These data suggest that HYAL is a novel and promising tool to use autologous MSC-like cells in the treatment of pulmonary fibrosis.

Background differentiate along a non-stromal lineage to become The hyaluronidases (HYAL s) are a group of enzymes  lung epithelial cells [7]. The bone marrow is the princi- that regulate hyaluronic acid (HA) metabolism and con- pal source for MSCs [8,9] but these cells have also been sequently remodel the extracellular matrix (ECM) [1].  isolated from the umbilical cord [10], fetal membranes These enzymes are produced by: mammals as a compo- [11] and other tissues. The use of MSCs to regenerate nent of seminal fluid, plasma and urine [1]; bacteria as a tissues has been reported as a promising therapy for the virulence factor [2,3]; and venomous animals as a non-  treatment of a variety of diseases [12,13]. However, cel- toxic component of venoms [1]. HYALs have been used lular therapy using MSCs has obstacles, including: the therapeutically due to their capacity to reduce biological difficulty of obtaining adequate numbers of these cells fluid viscosity, increase vascular permeability and render  to transplant; adverse effects of the cells or concomitant tissues more accessible to certain drugs [4]. immunosuppressive therapies; and the possibility of There is much interest in the HYAL-HA axis in the infection by opportunistic microorganisms [13-15]. treatment of inflammatory disorders [1]. While many  Increasingly, MSC-based therapies have been consid- studies demonstrated the involvement of HA in inflam- ered a promising new means of treating chronic lung matory responses, the involvement of HYALs has been  diseases such as pulmonary fibrosis, a progressive, less well studied [5,6]. Although prior investigations highly-lethal disorder for which very few effective thera- have measured tissue HA levels or HYAL messenger pies exist [7,13]. For example, MSCs were shown to RNA (mRNA) levels, few have directly assessed the ameliorate bleomycin-induced lung fibrosis in mice, an effect of HYALs on cell or organ function per se . effect that was associated with diminished lung damage Mesenchymal stem cells (M SCs) are pluripotent cells and ECM collagen deposition within the lung [16]. In that can differentiate into a variety of cells, including  addition, MSCs obtained from the umbilical cord were osteoblasts, myocytes, adipocytes and chondrocytes. recently reported to diminish bleomycin-induced fibrosis Recently, it has been demonstrated that MSC can [10]. In the light of this, we sought to examine the actions * Correspondence: [e-mail] of HYAL therapy on the lung microenvironment and on 1 Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, pulmonary inflammation. We investigated the effects of F P a a c u u l l o d , a R d ib e ei d r e ão Ci P ê r n et ci o a , s S F P, ar 1 m 40 ac 4 ê 0- u 9 ti 0 c 3 a , s B d ra e zi R l ibeirãoPreto,UniversidadedeSão intranasal inoculation (i.n.) of HYAL isolated from Full list of author information is available at the end of the article either bovine testes or Tityus serrulatus , a yellow © 2011 Bitencourt et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.