Plasticity of Airway Cell Proliferation and Gene Expression
Following Acute Naphthalene Injury.
Stripp, Barry R., Katy Maxson, Ranee Mera, and Gurmukh Singh.
Division of Pulmonary Biology, Children's Hospital Medical Center,
Cincinnati, Ohio 45229, Departments of Environmental Medicine and
Pediatrics, School of Medicine and Dentistry, University of
Rochester, Rochester, NY 14642, Department of Pathology, V.A. Medical
Center, Pittsburgh, PA 15240
APStracts 2:0042L, 1995.
Barry R. Stripp, Katy Maxson, Rane Mera, and Gurmukh Singh. Plasticity
of airway cell proliferation and gene expression following acute
naphthalene injury. Am. J. Physiol. 1995. The goal of this study was
to determine the temporal and spatial sequence of events that
accompany lung injury and repair following parenteral administration
of the Clara cell-specific cytotoxicant, naphthalene. Changes in
airway epithelial cells were evaluated by measuring alterations in
the expression of markers for differentiated Clara cells (CYPIIF and
Clara cell 10 kDa secretory protein, CC10), distal airway/alveolar
type II cells (surfactant protein B, SP-B) and for
cycling/proliferating cells (Cyclin dependent kinase 1; CDK1).
Naphthalene induced Clara cell cytotoxicity resulted in the
exfoliation of epithelial cells containing CC10 protein. This was
accompanied by a dramatic reduction in the abundance of mRNA's for
CC10 and CYPIIF. Large numbers of CDK1 mRNA positive cells were
identified in and around bronchioles and terminal bronchioles 48
hours after treatment. This cellular proliferation resulted in the
population of airways by immature epithelial cells lacking normal
levels of CC10 mRNA, but overexpressing SP-B mRNA. Seventy-two hours
after naphthalene treatment a reduction in CDK1 mRNA positive cells
was noted within bronchioles and terminal bronchioles at all
locations with the exception of airway bifurcation's. At airway
bifurcation's CDK1 mRNA appeared to be more abundant at the 72 hour
time point than at 48 hours. Comparison of these sections with serial
sections probed for CC10 mRNA demonstrated a correlation between the
expression of CDK1 and CC10 mRNA's at bifurcation's. Temporal
increases in the abundance of CC10 mRNA observed at later time points
were largely accounted for by the processive maturation of newly
repopulated cells neighboring bifurcation's in bronchioles. These
studies identify spatially distinct populations of cells that act in
concert to repopulate naphthalene injured airways and support the
notion that branchpoint cells play an important role in the
maturation of newly regenerated airway epithelial cells following
acute injury.
Received 2 December 1994; accepted in final form 27 February
1995.
APS Manuscript Number L344-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 4 April 1995.