Exhaustion of Airway Basal Progenitor Cells in Early and Established Chronic Obstructive Pulmonary Disease.
Am J Respir Crit Care Med
; 197(7): 885-896, 2018 04 01.
Article
en En
| MEDLINE
| ID: mdl-29211494
ABSTRACT
RATIONALE Up to 40% of smokers develop chronic obstructive pulmonary disease (COPD) over a period that spans decades. Despite the importance of COPD, much remains to be learned about susceptibility and pathogenesis, especially during early, prediagnostic stages of disease. Airway basal progenitor cells are crucial for lung health and resilience because of their ability to repair injured airways. In COPD, the normal airway epithelium is replaced with increased basal and secretory (mucous) cells and decreased ciliated cells, suggesting that progenitors are impaired. OBJECTIVES:
To examine airway basal progenitor cells and lung function in smokers with and without COPD.METHODS:
Bronchial biopsies taken from smokers at risk for COPD and lung cancer were used to acquire airway basal progenitor cells. They were evaluated for count, self-renewal, and multipotentiality (ability to differentiate to basal, mucous, and ciliated cells), and progenitor count was examined for its relationship with lung function. MEASUREMENTS AND MAINRESULTS:
Basal progenitor count, self-renewal, and multipotentiality were all reduced in COPD versus non-COPD. COPD progenitors produced an epithelium with increased basal and mucous cells and decreased ciliated cells, replicating the COPD phenotype. Progenitor depletion correlated with lung function and identified a subset of subjects without COPD with lung function that was midway between non-COPD with high progenitor counts and those with COPD.CONCLUSIONS:
Basal progenitor dysfunction relates to the histologic and physiologic manifestations of COPD and identifies a subset that may represent an early, prediagnostic stage of COPD, indicating that progenitor exhaustion is involved in COPD pathogenesis.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Madre
/
Fumar
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Enfermedad Pulmonar Obstructiva Crónica
/
Pulmón
Tipo de estudio:
Etiology_studies
/
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
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Screening_studies
Límite:
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Am J Respir Crit Care Med
Asunto de la revista:
TERAPIA INTENSIVA
Año:
2018
Tipo del documento:
Article