The cellular response in naphthalene-induced clara cell injury and
bronchiolar epithelial repair in the mouse.
Van Winkle, Laura S., Alan R. Buckpitt, Susan J. Nishio, Jonathan M.
Isaac, and Charles G. Plopper.
Department of Anatomy, Physiology and Cell Biology and Department
of Molecular Biosciences, School of Veterinary Medicine, Occupational
and Environmental Health Unit, School of Medicine, University of
California-Davis, Davis, CA 95616-8732
APStracts 2:0173L, 1995.
Clara cells, progenitors for bronchiolar epithelium, are also primary
targets for metabolically activated pulmonary cytotoxicants and have
an abundance of the cytochrome P450 monooxygenases required for
xenobiotic metabolism. To define the repair pattern following massive
Clara cell injury, mice were treated with naphthalene, and lungs
evaluated 1-14 days post injury (DPI). Clara cells of terminal
bronchioles were vacuolated and swollen 1 DPI, exfoliated 2 DPI, and
resembled controls at 14 DPI. The volume fraction of vacuolated cells
was highest 1 and 2 DPI, minimal 5-7 DPI. The volume fraction of
normal nonciliated cells decreased 40% 1 DPI. Cell proliferation
increased within epithelium and interstitium 1 DPI, was maximal 2 DPI
and at all other time points was similar to baseline levels.
Expression of Clara cell differentiation markers was barely
detectable in terminal bronchiolar epithelium at 1 and 2 DPI, clearly
detectable 4 DPI, and gradually returned to control levels 5-14 DPI.
We conclude that bronchiolar epithelial repair after naphthalene
injury involves: distinct phases of proliferation and
differentiation, proliferation of cells that are not differentiated
Clara cells and interaction of multiple cell types including
nontarget cells.
Received 13 February 1995; accepted in final form 27 September
1995
APS Manuscript Number L044-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95