Distinct pattern of immune cell population in the lung of human fetuses with cystic fibrosis

Background: Airway inflammation and infection are early events in cystic fi brosis (CF) pathogenesis. The existence of an imbalance in the immune cell population of the CF fetal airway before infection remains completely unkno wn. Objective: The aim of this study was to determine whether early signs of in flammation are observed in CF airways during human fetal development. Methods: Tracheas and lungs were collected from 21 CF and 16 non-CF fetuses . In tissue sections, the numbers of neutrophils, mast cells, macrophages, and B and T lymphocytes were quantitatively analyzed by means of image cyto metry. The presence of IL-4, IL-6, IL-8, IL-10, RANTES, IFN-gamma, TNF-alph a and NF kappaB and its inhibitor I kappaB-alpha was qualitatively evaluate d by immunofluorescent staining. Results: During fetal airway development, epithelial and glandular differen tiation, as well as the distribution of inflammatory markers, was similar i n CF and non-CF tissues. Significant differences between CF and non-CF feta l airways were observed only in the numbers of mast cells and macrophages. In the CF trachea, the mast cell number increased slowly but continuously, whereas in the non-CF trachea this number rapidly reached a plateau. In the CF lung, the macrophage number increased with time, whereas in the non-CF lung it decreased. Conclusion: Although no intrinsic inflammation was demonstrated, we observe d a distinct appearance of mast cells and macrophages in CF airways in comp arison with non-CF airways during fetal development. These 2 cell populatio ns were greater in CF airways at a late stage of fetal development, suggest ing their possible involvement in the early onset of inflammation in CF inf ants.