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 fibrosis (CF) pathogenesis. The existence of an imbalance in the immune cell population of the CF fetal airway before infection remains completely unknown.


OBJECTIVE
The aim of this study was to determine whether early signs of inflammation 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 cytometry. The presence of IL-4, IL-6, IL-8, IL-10, RANTES, IFN-gamma, TNF-alpha, and NF kappa B and its inhibitor I kappa B-alpha was qualitatively evaluated by immunofluorescent staining.


RESULTS
During fetal airway development, epithelial and glandular differentiation, as well as the distribution of inflammatory markers, was similar in CF and non-CF tissues. Significant differences between CF and non-CF fetal 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.


CONCLUSIONS
Although no intrinsic inflammation was demonstrated, we observed a distinct appearance of mast cells and macrophages in CF airways in comparison with non-CF airways during fetal development. These 2 cell populations were greater in CF airways at a late stage of fetal development, suggesting their possible involvement in the early onset of inflammation in CF infants.
Hubeau
C
C
Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 514, Institut Fédératif de Recherche (IFR) 53, Université de Reims Champagne-Ardenne, Reims, France.
Puchelle
E
E
Gaillard
D
D
D015703:Antigens, CD / Q000302:isolation & purification; D003550:Cystic Fibrosis / Q000473:pathology*; D016207:Cytokines / Q000302:isolation & purification; D005260:Female; D005315:Fetal Diseases / Q000473:pathology*; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000302:isolation & purification; D007107:Immune System / Q000473:pathology*; D007962:Leukocytes; D008168:Lung / Q000473:pathology; D008264:Macrophages; D008407:Mast Cells; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012137:Respiratory System / Q000473:pathology*; D014132:Trachea / Q000473:pathology
D015703:Antigens, CD; D016207:Cytokines; D020672:I-kappa B Proteins