EXPRESSION OF THYROID TRANSCRIPTION FACTOR-I (TTF-1) IN FETAL AND NEONATAL HUMAN LUNG

We assessed the immunohistochemical localization of thyroid transcript ion factor-1 (TTF-1) in the lungs of 24 human fetuses (11-23 weeks), t hree infants without pulmonary pathology (36-42 weeks), and 24 infants (2 days-6.5 months) with hyaline membrane disease (HMD) or bronchopul monary dysplasia (BPD). TTF-1 was detected in fetal lung epithelial ce ll nuclei by 11 weeks' gestation. Budding tips of terminal airways had prominently labeled nuclei, By 17 weeks, labeling was present in scat tered nonciliated columnar and cuboidal cells, Throughout gestation, T TF-1 nuclear staining was prominent in airways abutting pleural, perib ronchial, or perivascular connective tissue, being less prominent in c enters of lobules, By 23 weeks, many cells in cuboidal but not columna r cell-lined airways had labeled nuclei, At term, TTF-1 was detected p rimarily in Type II epithelial cells. In HMD with alveolar hemorrhage, edema, or airway collapse, little or no TTF-1 was present except in o pen terminal airways, In BDP lungs, TTF-1 was absent in areas of alveo lar collapse or infection, being present in regenerating open airways. The temporal-spatial distribution of TTF-1, in general, follows patte rns of distribution of surfactant protein-B in developing and patholog ical lungs, consistent with its role in the regulation of epithelial c ell gene expression in the lung.