Am. J. Respir. Cell Mol. Biol., Vol 17, No. 6, 12 1997, 691-701.
Increased type I procollagen mRNA in airways and pulmonary vessels after vagal denervation in rats
TW Carver Jr, SK Srinathan, CR Velloff and JJ Perez Fontan
The Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
To test the hypothesis that increased airway strain resulting from lung
denervation initiates a fibroproliferative response in the airways, we
compared the transcriptional expressions of alpha1(I)-procollagen and
tropoelastin in the lungs of rats subjected to unilateral vagal
denervation, unilateral vagal denervation combined with ipsilateral
phrenectomy, or thoracotomy without denervation (controls). We found
increases in alpha1(I)-procollagen messenger ribonucleic acids (mRNAs) in
the submucosa of the airways and the adventitia of airways and pulmonary
vessels of the denervated lungs in 31% of the rats subjected to unilateral
denervation (with and without phrenectomy), and in none of the controls.
The increased transcripts were associated with collagen deposition in the
peribronchial and perivascular tissue, and occasionally with cell
proliferation leading to occlusion of the airway and vascular lumina.
Unilateral phrenectomy did not decrease the frequency with which production
of Type I procollagen was upregulated, suggesting that the upregulation was
not entirely dependent on airway strain. Tropoelastin expression was not
influenced by denervation. Our results indicate that the autonomic nervous
system has a previously unsuspected trophic influence on collagen synthesis
in the airways and pulmonary vessels. Abolition of this influence by
denervation may lead to structural changes analogous to those observed in
bronchiolitis obliterans after lung transplantation.
