Interleukin-8 release by endothelial colony-forming cells isolated from idiopathic pulmonary fibrosis patients might contribute to their pathogenicity
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.
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.
KeywordsEndothelial progenitor cells Endothelial colony-forming cells Liquid biopsy Interleukin-8 Idiopathic pulmonary fibrosis
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.
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