Am. J. Respir. Cell Mol. Biol.,
Volume 19, Number 3, September, 1998 419-425
Influence of Mechanical Stretch on Thrombin Regulation by Fetal
Mixed Lung Cells
Anthony K. C.
Chan,
Bryan
Baranowski,
Leslie
Berry,
Mingyao
Liu,
Bijan
Rafii,
Martin
Post,
Hugh
O'Brodovich,
Paul
Monagle,
and
Maureen
Andrew
The MRC Group in Lung Development, Respiratory Research Division, and the Neonatal Research Division of
The Hospital for Sick Children, Toronto; and the Departments of Pediatrics of the University of Toronto, Toronto;
and McMaster University, Hamilton, Ontario, Canada
Respiratory distress syndrome (RDS) is characterized by intrapulmonary fibrin deposition, which can adversely affect surfactant function, and stimulate fibroblast proliferation, which may contribute to the development of bronchopulmonary dysplasia (BPD). We speculated that the premature lung may have impaired
regulation of thrombin, thus making preterm infants susceptible to fibrin formation within the lung. Therefore, we studied the effect of stretch, which simulates fetal breathing movements (FBMs), on the generation and inhibition of a key hemostatic enzyme
thrombinby rat fetal mixed lung cells (FMLCs). Our
results showed that stretch induced glycosaminoglycan production with increased antithrombin activity
due to an increase in the concentration of active chondroitin sulfate. Stretch downregulated secretion of
tissue factor procoagulant activity, which may lead to decreased thrombin generation on the surface of
FMLCs. Overall, stretch enhanced the local control of thrombin by FMLCs. These results suggest that premature infants, who will have experienced less FBM, may have impaired thrombin regulation. Impaired
thrombin regulation likely contributes to increased fibrin deposition and, potentially, the development of
BPD.
