期刊
ANGIOGENESIS
卷 22, 期 2, 页码 325-339出版社
SPRINGER
DOI: 10.1007/s10456-018-09659-5
关键词
Endothelial progenitor cells; Endothelial colony-forming cells; Liquid biopsy; Interleukin-8; Idiopathic pulmonary fibrosis
资金
- Chancellerie des Universites (Legs Poix)
- PROMEX STIFTUNG FUR DIE FORSCHUNG foundation
- AP-HP
- INSERM (contrat d'accueil)
- PRES
IntroductionIdiopathic 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 resultsECFCs 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.ConclusionTo 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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