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1 The Cardiovascular Institute,
Earlier work from this laboratory showed that
abnormal fibroblast phenotypes isolated from fibrotic human lung
produce factor(s) capable of inducing apoptosis and necrosis of
alveolar epithelial cells in vitro [B. D. Uhal, I. Joshi, A. True, S. Mundle, A. Raza, A. Pardo, and M. Selman. Am.
J. Physiol. 269 (Lung Cell. Mol. Physiol. 13): L819-L828, 1995]. To determine
whether epithelial cell death is associated with proximity to abnormal
fibroblasts in vivo, the spatial distribution of epithelial cell loss,
DNA fragmentation, and myofibroblasts was examined in the same tissue specimens used previously for fibroblast isolation. Paraffin sections of normal and fibrotic human lung were subjected to in situ end labeling (ISEL) of fragmented DNA and simultaneous immunolabeling of
-smooth muscle actin (-SMA); replicate samples were subjected to
electron microscopy and detection of collagens by the picrosirius red
technique. Normal human lung exhibited very little labeling except for
positive -SMA immunoreactivity of smooth muscle surrounding bronchi
and vessels. In contrast, fibrotic human lung exhibited moderate to
heavy ISEL of interstitial, cuboidal epithelial, and free alveolar
cells. ISEL of the alveolar epithelium was not distributed uniformly
but was most intense immediately adjacent to underlying foci of
-SMA-positive fibroblast-like interstitial cells. Both electron
microscopy and picrosirius red confirmed epithelial cell apoptosis,
necrosis, and cell loss adjacent to foci of collagen accumulation
surrounding fibroblast-like cells. These results demonstrate that the
cuboidal epithelium of the fibrotic lung contains dying as well as
proliferating cells and support the hypothesis that alveolar epithelial
cell death is induced by abnormal lung fibroblasts in vivo as it is in vitro.
cuboidalization; type II pneumocytes; programmed cell death; contractile interstitial cells
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R. Wang, A. Zagariya, O. Ibarra-Sunga, C. Gidea, E. Ang, S. Deshmukh, G. Chaudhary, J. Baraboutis, G. Filippatos, and B. D. Uhal Angiotensin II induces apoptosis in human and rat alveolar epithelial cells Am J Physiol Lung Cell Mol Physiol, May 1, 1999; 276(5): L885 - L889. [Abstract] [Full Text] [PDF]
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