M. Kasper et al., DISTINCT EXPRESSION PATTERNS OF CD44 ISOFORMS DURING HUMAN LUNG DEVELOPMENT AND IN PULMONARY FIBROSIS, American journal of respiratory cell and molecular biology, 13(6), 1995, pp. 648-656
The transmembrane glycoprotein CD44 represents a family of molecules,
all encoded by one gene. The variability of the isoforms is generated
by alternative splicing of the nuclear RNA. Apart from the abundant st
andard form (CD44s), the variant isoforms (CD44v) are mostly restricte
d to epithelia. The present study demonstrates the expression of CD44s
and CD44v isoforms in embryonic and fetal lungs and in normal and pat
hologically altered (pulmonary fibrosis after radio- or chemotherapy)
human adult pulmonary tissues. Using double immunofluorescence and avi
din biotin complex (ABC) techniques on paraffin sections, presence of
CD44s and CD44v isoforms (CD44v4, CD44v6, CD44v9) has been analyzed. I
n normal lung tissue, CD44s is present at the cell surface of alveolar
macrophages, in some interstitial cells and in epithelial cells. It i
s also present in epithelial and non-epithelial cells during lung deve
lopment. CD44v isoforms containing exon v6 and v9 encoded epitopes are
selectively detectable in normal epithelial cells with a strong basol
ateral distribution pattern in the entire population of type II pneumo
cytes and in basal cells of the bronchial epithelium. During developme
nt exon v9 encoded isoforms appear at the pseudoglandular stage, where
as CD44v6 has only been found at the saccular stage. Examination of 12
fibrotic lung samples has revealed major alterations in the CD44 expr
ession in comparison to normal lung tissue. These changes include cyto
plasmic deposits of CD44s in alveolar epithelial cells and reduced exp
ression of the CD44v6 and CD44v9 isoforms in alveolar epithelial and b
ronchial epithelial cells. The results suggest that CD44v isoforms may
be utilized by type II pneumocytes in epithelial-mesenchymal interact
ions and in the maintenance of the pulmonary histoarchitecture. Pathol
ogic alterations in pulmonary fibrosis are accompanied by disruption o
f the histoarchitecture and loss of CD44v isoforms.