Ontogeny of protein expression of CD208, surfactant protein A and D, thyroid transcription factor‐1 (TTF‐1), and cell proliferation antigen (Ki‐67) in lung epithelia of pre‐ and full‐term lambs

Abstract

Children born preterm have an increased susceptibility to respiratory syncytial virus (RSV) compared to those born full-term. RSV initially infects and damages epithelial cells, which are important for adaptive and innate immune responses such as expression of surfactant proteins A (SP-A) and D (SP-D) which are known to protect against RSV infection. However, the extent of expression preterm, as well as the effect of cell proliferation and differentiation has on the production of these proteins have not been determined. SP-A and D protein production as well as the extent of cell proliferation (Ki67 expression) and differentiation (CD208 antigen cells) and Thyroid Transcription Factor-1 (TTF-1; a SP transcription factor) were determined by immunohistochemistry in lung from preterm (80% gestation), full-term, and post-term (15 days of age) lambs. Cell differentiation (CD208+ cells) increased significantly with age; however, no significant changes were seen with proliferation (Ki67 antigen), SP-AD, or TTF-1. SP-AD expression was present in bronchial and bronchiolar epithelial cells, and occasional alveolar epithelial cells in all age groups, TTF-1 was present in non-ciliated airway cells and type II cells as described previously. This work suggests that cell differentiation increases with gestation and that SP-A and D production is present in bronchioles and alveoli in late gestation and at birth. Supported NIH NIAID Awards 5R01AI062787-02 and 5K08AI055499-03, USDA/CSREES/NRI-CGP 2003-35204-13492, and the JG Salsbury Endowment.