Alveolar fluid in acute respiratory distress syndrome promotes fibroblast migration: Role of platelet-derived growth factor pathway
Critical Care Medicine, 06/20/2012
Piednoir P et al. – The results suggest that during acute lung injury, fibroblast migration is modulated by bronchoalveolar lavage fluids through a platelet–derived growth factor/platelet–derived growth factor–sRα balance. Migration is associated with clinical severity and patient 28–day mortality.Methods
- Ninety–three ventilated patients requiring bronchoalveolar lavage fluids were enrolled (48 with acute respiratory distress syndrome, 33 with acute lung injury, and 12 ventilated patients without acute lung injury/acute respiratory distress syndrome).
- After bronchoalveolar lavage fluids collection during standard care, the patients were followed up for 28days and clinical outcomes were recorded.
- Migration assays were performed by using a Transwell model; bronchoalveolar lavage fluids platelet–derived growth factor and soluble platelet–derived growth factor receptor–α were characterized by Western blot and measured by ELISA.
- Most of the bronchoalveolar lavage fluids inhibited basal fibroblast migration.
- Bronchoalveolar lavage fluids chemotactic index increased with severity of lung injury (28% in patients without acute lung injury/acute respiratory distress syndrome and with acute lung injury vs. 91% in acute respiratory distress syndrome patients; p=.016).
- In acute lung injury/acute respiratory distress syndrome patients, inhibition of basal fibroblast migration by bronchoalveolar lavage fluids below 52% was independently associated with a lower 28–day mortality (odds ratio [95% confidence interval] 0.313 [0.10–0.98], p=.046).
- Platelet–derived growth factor–related peptides and soluble platelet–derived growth factor–Rα were detected in all bronchoalveolar lavage fluids from acute lung injury/acute respiratory distress syndrome patients.
- The effect of bronchoalveolar lavage fluids stimulating migration was inhibited by a specific platelet–derived growth factor receptor inhibitor (AG1296).
- Bronchoalveolar lavage fluids inhibiting migration reversed the effect of rh–platelet–derived growth factor–BB and reduced by 40% the binding of 125I–platelet–derived growth factor–BB to fibroblast cell surface in favor of a role for platelet–derived growth factor–sRα.