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

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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.

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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).

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Authors and Affiliations

  1. Hematology Department, AP-HP, European Georges Pompidou Hospital, 20 rue Leblanc, 75015, Paris, France

    Adeline Blandinières, Nicolas Gendron, Sebastien Bertil, Pascale Gaussem & David M. Smadja

  2. Paris Descartes University, Sorbonne Paris Cité, Paris, France

    Adeline Blandinières, Nicolas Gendron, Nour Bacha, Ivan Bièche, Richard Chocron, Nathalie Nevo, Elisa Rossi, Séverine Lecourt, Anna Lokajczyk, Virginie Mignon, Audrey Cras, Pascale Gaussem, Dominique Israël-Biet & David M. Smadja

  3. Inserm UMR-S1140, Paris, France

    Adeline Blandinières, Nicolas Gendron, Nour Bacha, Nathalie Nevo, Elisa Rossi, Séverine Lecourt, Anna Lokajczyk, Alexandre Kisaoglu, Audrey Cras, Pascale Gaussem, Dominique Israël-Biet & David M. Smadja

  4. Pharmacogenomics Unit, Department of Genetics, Institut Curie, Paris, France

    Ivan Bièche

  5. Emergency Medicine Department, AP-HP, European Georges Pompidou Hospital, Paris, France

    Richard Chocron

  6. Inserm UMR-S970, PARCC, Paris, France

    Richard Chocron

  7. Avicenne Hospital, Respiratory Medicine Department, AP-HP, Paris, France

    Hilario Nunes & Dominique Valeyre

  8. Bichat Hospital, Respiratory Medicine Department, AP-HP, Paris, France

    Bruno Crestani

  9. Biostatistics Unit, AP-HP, Saint Louis Hospital, Paris Diderot University, Paris, France

    Sylvie Chevret

  10. Cellular and Molecular Imaging Facility, Faculty of Pharmacy of Paris, Inserm US 25, CNRS UMS 3612, Paris Descartes University, Paris, France

    Virginie Mignon

  11. Respiratory Medicine Department, AP-HP, European Georges Pompidou Hospital, Paris, France

    Karine Juvin & Dominique Israël-Biet

  12. Cell Therapy Departement, AP-HP, Saint Louis Hospital, Paris, France

    Audrey Cras

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  1. Adeline Blandinières
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Blandinières, A., Gendron, N., Bacha, N. et al. Interleukin-8 release by endothelial colony-forming cells isolated from idiopathic pulmonary fibrosis patients might contribute to their pathogenicity. Angiogenesis 22, 325–339 (2019). https://doi.org/10.1007/s10456-018-09659-5

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