Glial cell-derived neurotrophic factor expression in normal human lung and congenital cystic adenomatoid malformation.

Abstract

CONTEXT:

It has been recently suggested that dysregulation of developmental factors and disruption of cell turnover could play a role in the pathogenesis of congenital cystic adenomatoid malformation of the lung (CCAM). The glial cell-derived neurotrophic factor (GDNF) is a growth factor involved in organogenesis, and the temporal pattern of GDNF expression suggests that this factor may play a role in lung development.

DESIGN:

We studied GDNF expression by immunohistochemistry in postnatally resected CCAM of the lung (n = 10), normal fetal lung (n = 5), and normal postnatal lung (n = 5). We also studied the association between GDNF expression and both cell proliferation and apoptosis.

RESULTS:

GDNF was expressed in both epithelial and endothelial compartments of normal fetal lung, whereas no expression was found in normal postnatal lung. In contrast, in CCAM tissue, there was strong GDNF immunostaining that was restricted to epithelial cells. The percentage of proliferating epithelial cells was higher in CCAM tissue than in normal postnatal lung (6.3% vs 1.7%, P <.005). Apoptotic bodies were found in the mesenchyme of both normal fetal lung and CCAM tissue, whereas virtually no apoptotic bodies were detected in normal postnatal lung.

CONCLUSIONS:

Abnormal GDNF expression in CCAM suggests a dysregulation of the GDNF signaling pathway and argues in favor of a focal arrest in maturation during development. GDNF expression in lung tissue seems to be correlated with cell proliferation, suggesting that this factor could play a role in the growth of both fetal lung and CCAM.

• Authors: Gaelle Fromont-Hankard, Pascale Philippe-Chomette, Anne-Lise Delezoide, Catherine Nessmann, Yves Aigrain, Michel Peuchmaur
• Journal: Archives of pathology & laboratory medicine (Arch Pathol Lab Med) Vol. 126 Issue 4 Pg. 432-6 (Apr 2002) ISSN: 0003-9985 [Print] United States
• PMID: 11900567 (Publication Type: Journal Article)

Chemical References

• GDNF protein, human
• Glial Cell Line-Derived Neurotrophic Factor
• Nerve Growth Factors
• Nerve Tissue Proteins

Topics

• Apoptosis
• Cell Division
• Cystic Adenomatoid Malformation of Lung, Congenital (metabolism, pathology, surgery)
• Female
• Fluorescent Antibody Technique, Indirect
• Gestational Age
• Glial Cell Line-Derived Neurotrophic Factor
• Humans
• Immunoenzyme Techniques
• In Situ Nick-End Labeling
• Infant
• Infant, Newborn
• Lung (abnormalities, metabolism, surgery)
• Male
• Mitotic Index
• Nerve Growth Factors
• Nerve Tissue Proteins (biosynthesis)