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Angiogenesis

pp 1–15 | Cite as

Interleukin-8 release by endothelial colony-forming cells isolated from idiopathic pulmonary fibrosis patients might contribute to their pathogenicity

  • Adeline Blandinières
  • Nicolas Gendron
  • Nour Bacha
  • Ivan Bièche
  • Richard Chocron
  • Hilario Nunes
  • Nathalie Nevo
  • Elisa Rossi
  • Bruno Crestani
  • Séverine Lecourt
  • Sylvie Chevret
  • Anna Lokajczyk
  • Virginie Mignon
  • Alexandre Kisaoglu
  • Karine Juvin
  • Sebastien Bertil
  • Dominique Valeyre
  • Audrey Cras
  • Pascale Gaussem
  • Dominique Israël-Biet
  • David M. SmadjaEmail author
Original Paper

Abstract

Introduction

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by obliteration of alveolar architecture, resulting in declining lung function and ultimately death. Pathogenic mechanisms involve a concomitant accumulation of scar tissue together with myofibroblasts activation and a strong abnormal vascular remodeling. Endothelial progenitor cells (ECFC subtype) have been investigated in several human lung diseases as a potential actor in IPF. We previously demonstrated that ECFCs are down-regulated in IPF in contrast to healthy controls. We postulated here that ECFCs might behave as a liquid biopsy in IPF patients and that they exert modified vasculogenic properties.

Methods and results

ECFCs isolated from controls and IPF patients expressed markers of the endothelial lineage and did not differ concerning adhesion, migration, and differentiation in vitro and in vivo. However, senescent and apoptotic states were increased in ECFCs from IPF patients as shown by galactosidase staining, p16 expression, and annexin-V staining. Furthermore, conditioned medium of IPF-ECFCs had increased level of interleukin-8 that induced migration of neutrophils in vitro and in vivo. In addition, an infiltration by neutrophils was shown in IPF lung biopsies and we found in a prospective clinical study that a high level of neutrophils in peripheral blood of IPF patients was associated to a poor prognosis.

Conclusion

To conclude, our study shows that IPF patients have a senescent ECFC phenotype associated with an increased IL-8 secretion potential that might contribute to lung neutrophils invasion during IPF.

Keywords

Endothelial progenitor cells Endothelial colony-forming cells Liquid biopsy Interleukin-8 Idiopathic pulmonary fibrosis 

Notes

Acknowledgements

We thank the animal Platform, CRP2 – UMS 3612 CNRS – US25 Inserm-IRD – Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, France. We are indebted to cell therapy department of Saint-Louis Hospital (AP-HP, Paris) for cord-blood samples. This work was supported by grants of the Chancellerie des Universités (Legs Poix), PRES, and PROMEX STIFTUNG FUR DIE FORSCHUNG foundation. A. Blandinières was supported by grants from AP-HP and INSERM (contrat d’accueil).

Compliance with ethical standards

Conflict of interest

The authors do not have any conflicts of interest to disclose.

Supplementary material

10456_2018_9659_MOESM1_ESM.docx (33.6 mb)
Supplementary material 1 (DOCX 34417 KB)

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Adeline Blandinières
    • 1
    • 2
    • 3
  • Nicolas Gendron
    • 1
    • 2
    • 3
  • Nour Bacha
    • 2
    • 3
  • Ivan Bièche
    • 2
    • 4
  • Richard Chocron
    • 2
    • 5
    • 6
  • Hilario Nunes
    • 7
  • Nathalie Nevo
    • 2
    • 3
  • Elisa Rossi
    • 2
    • 3
  • Bruno Crestani
    • 8
  • Séverine Lecourt
    • 2
    • 3
  • Sylvie Chevret
    • 9
  • Anna Lokajczyk
    • 2
    • 3
  • Virginie Mignon
    • 2
    • 10
  • Alexandre Kisaoglu
    • 3
  • Karine Juvin
    • 11
  • Sebastien Bertil
    • 1
  • Dominique Valeyre
    • 7
  • Audrey Cras
    • 2
    • 3
    • 12
  • Pascale Gaussem
    • 1
    • 2
    • 3
  • Dominique Israël-Biet
    • 2
    • 3
    • 11
  • David M. Smadja
    • 1
    • 2
    • 3
    Email author return OK on get
  1. 1.Hematology DepartmentAP-HP, European Georges Pompidou HospitalParisFrance
  2. 2.Paris Descartes University, Sorbonne Paris CitéParisFrance
  3. 3.Inserm UMR-S1140ParisFrance
  4. 4.Pharmacogenomics Unit, Department of GeneticsInstitut CurieParisFrance
  5. 5.Emergency Medicine DepartmentAP-HP, European Georges Pompidou HospitalParisFrance
  6. 6.Inserm UMR-S970, PARCCParisFrance
  7. 7.Avicenne Hospital, Respiratory Medicine DepartmentAP-HPParisFrance
  8. 8.Bichat Hospital, Respiratory Medicine DepartmentAP-HPParisFrance
  9. 9.Biostatistics UnitAP-HP, Saint Louis Hospital, Paris Diderot UniversityParisFrance
  10. 10.Cellular and Molecular Imaging Facility, Faculty of Pharmacy of ParisInserm US 25, CNRS UMS 3612, Paris Descartes UniversityParisFrance
  11. 11.Respiratory Medicine DepartmentAP-HP, European Georges Pompidou HospitalParisFrance
  12. 12.Cell Therapy DepartementAP-HP, Saint Louis HospitalParisFrance

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