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Influence of mechanical stretch on thrombin regulation by fetal mixed lung cells
A K Chan1, B Baranowski, L Berry
1The 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, Canada.
Insights
Premature infants may develop bronchopulmonary dysplasia due to impaired thrombin regulation. Fetal breathing movements help control thrombin, reducing lung fibrin deposition in developing lungs.
Area of Science:
- Pulmonary Medicine
- Neonatology
- Hemostasis
Background:
- Respiratory distress syndrome (RDS) involves lung fibrin deposition, potentially leading to bronchopulmonary dysplasia (BPD).
- Preterm infants may have impaired thrombin regulation, increasing susceptibility to lung fibrin formation.
- Fetal breathing movements (FBMs) are crucial for lung development and may influence hemostasis.
Purpose of the Study:
- To investigate the effect of mechanical stretch, simulating FBMs, on thrombin generation and inhibition by rat fetal mixed lung cells (FMLCs).
- To explore the role of FBMs in regulating local hemostasis within the developing lung.
Main Methods:
- Cultured rat FMLCs were subjected to mechanical stretch.
- Thrombin generation, tissue factor activity, and glycosaminoglycan production were measured.
- Antithrombin activity and chondroitin sulfate concentration were assessed.
Main Results:
- Mechanical stretch increased glycosaminoglycan production and antithrombin activity.
- Stretch led to increased active chondroitin sulfate concentration.
- Stretch downregulated tissue factor secretion, reducing thrombin generation on FMLC surfaces.
- Overall, stretch enhanced local thrombin control by FMLCs.
Conclusions:
- Simulated fetal breathing movements enhance local thrombin control in developing lungs.
- Preterm infants with reduced FBMs may exhibit impaired thrombin regulation.
- Impaired thrombin regulation could contribute to increased lung fibrin deposition and BPD development.
Abstract:
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-thrombin-by 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.