Growth of putative progenitors of type II pneumocytes in culture of human cystic fibrosis alveoli.
Alveolar type II pneumocytes are thought to be progenitor cells capable of self-renewal and differentiation into type I pneumocytes. Nevertheless, the existence of an alveolar stem cell has been postulated. In lungs from patients with cystic fibrosis, the alveolar epithelium is damaged with ulceration and subsequent regeneration. We characterized alveolar modifications histologically and immunohistochemically in the pulmonary tissue of a patient homozygous for the DeltaF508 mutation. Alveoli were of variable size and surrounded by an inflammatory infiltrate. They were lined by a continuous layer of cuboidal cells with very weak proliferative activity. These cells resembled type II pneumocytes. They expressed thyroid transcription factor-1, cystic fibrosis transmembrane conductance regulator, cytokeratin 7 and contained lamellar bodies. Weak expression of cytokeratin 5 considered to be a marker of progenitor cells of the bronchial and bronchiolar epithelium was detected. Explantation of this alveolar epithelium produced primary cultures and subcultures of epithelial cells that had acquired proliferative properties showing signs of dedifferentiation with a loss of lamellar bodies and a lack of expression of thyroid transcription factor-1. Persistence of the expression of cytokeratin 7 and a strong expression of cytokeratin 5 were observed. The culture conditions were thought to have circumvented the inhibition of proliferation observed in vivo due to the inflammatory peri-alveolar environment. They thus favored the multiplication of a population of cells co-expressing cytokeratin 5 and certain characteristics of type II pneumocytes. The presence of these cells of intermediate phenotype is indicative of the existence of immature precursors for type II pneumocytes.
Hollande
Etienne
E
Laboratoire de Biologie Cellulaire et Moléculaire des Epithéliums (E.A. 3032), Université Paul Sabatier, 38, rue des Trente-six Ponts, 31400 Toulouse, France. hollande@cict.fr
Cantet
Sylvie
S
Ratovo
Ginette
G
Daste
Ghislaine
G
Brémont
François
F
Fanjul
Marjorie
M
D015415:Biomarkers; D002478:Cells, Cultured; D002648:Child; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D053552:Keratin-7; D007633:Keratins / Q000378:metabolism; D008168:Lung / Q000166:cytology*; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000648:ultrastructure; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D015415:Biomarkers; C507497:KRT7 protein, human; D053552:Keratin-7; D007633:Keratins