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Stem Cell Reviews and Reports

, Volume 14, Issue 2, pp 223–235 | Cite as

Endothelial Microparticles are Associated to Pathogenesis of Idiopathic Pulmonary Fibrosis

  • Nour C. Bacha
  • Adeline Blandinieres
  • Elisa Rossi
  • Nicolas Gendron
  • Nathalie Nevo
  • Séverine Lecourt
  • Coralie L. Guerin
  • Jean Marie Renard
  • Pascale Gaussem
  • Eduardo Angles-Cano
  • Chantal M. Boulanger
  • Dominique Israel-Biet
  • David M. Smadja
Article

Abstract

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by obliteration of alveolar architecture, resulting in declining lung function and ultimately death. Pathogenic mechanisms remain unclear but involve a concomitant accumulation of scar tissue together with myofibroblasts activation. Microparticles (MPs) have been investigated in several human lung diseases as possible pathogenic elements, prognosis markers and therapeutic targets. We postulated that levels and cellular origins of circulating MPs might serve as biomarkers in IPF patients and/or as active players of fibrogenesis. Flow cytometry analysis showed a higher level of Annexin-V positive endothelial and platelet MPs in 41 IPF patients compared to 22 healthy volunteers. Moreover, in IPF patients with a low diffusing capacity of the lung for carbon monoxide (DLCO<40%), endothelial MPs (EMPs) were found significantly higher compared to those with DLCO>40% (p = 0.02). We then used EMPs isolated from endothelial progenitor cells (ECFCs) extracted from IPF patients or controls to modulate normal human lung fibroblast (NHLF) properties. We showed that EMPs did not modify proliferation, collagen deposition and myofibroblast transdifferentiation. However, EMPs from IPF patients stimulated migration capacity of NHLF. We hypothesized that this effect could result from EMPs fibrinolytic properties and found indeed higher plasminogen activation potential in total circulating MPs and ECFCs derived MPs issued from IPF patients compared to those isolated from healthy controls MPs. Our study showed that IPF is associated with an increased level of EMPs in the most severe patients, highlighting an active process of endothelial activation in the latter. Endothelial microparticles might contribute to the lung fibroblast invasion mediated, at least in part, by a fibrinolytic activity.

Notes

Acknowledgements

This work was supported by grants of Chancellerie des Universities (Legs Poix) and Coeny-maeva charitable foundation.

Nour C. Bacha is supported by a grant from « Fonds de dotation pour la Recherche en Santé Respiratoire ».

We thank the technicians and engineers of hematology department of Georges Pompidou hospital, in particular Sebastien Bertil, Alexandre Kisaoglou, Florence Desvard, Nadège Ochat and Yann Burnel.

Compliance with Ethical Standards

Declaration of Interest

Authors declare no conflict of interest related to this work.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Nour C. Bacha
    • 1
    • 2
  • Adeline Blandinieres
    • 1
    • 2
    • 3
  • Elisa Rossi
    • 1
    • 2
  • Nicolas Gendron
    • 1
    • 2
    • 3
  • Nathalie Nevo
    • 1
    • 2
  • Séverine Lecourt
    • 1
  • Coralie L. Guerin
    • 4
  • Jean Marie Renard
    • 2
    • 5
  • Pascale Gaussem
    • 1
    • 2
    • 3
  • Eduardo Angles-Cano
    • 1
    • 2
  • Chantal M. Boulanger
    • 2
    • 5
  • Dominique Israel-Biet
    • 1
    • 2
    • 6
  • David M. Smadja
    • 1
    • 2
    • 3
  1. 1.Inserm UMR-S1140ParisFrance
  2. 2.Sorbonne Paris CiteUniversité Paris DescartesParisFrance
  3. 3.Hematology Department and UMR-S1140AP-HP, European Hospital Georges PompidouParisFrance
  4. 4.National Cytometry Platform, Department of Infection and ImmunityLuxembourg Institute of HealthLuxembourgFrance
  5. 5.Inserm UMR-S970, PARCCParisFrance
  6. 6.Pneumology DepartmentAP-HP, European Hospital Georges PompidouParisFrance

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