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Alveolar fluid in acute respiratory distress syndrome promotes fibroblast migration
| Content Provider | Scilit |
|---|---|
| Author | Piednoir, Pascale Quesnel, Christophe Nardelli, Laurent Leçon, Véronique Bouadma, Lila Lasocki, Sigismond Philip, Ivan Mailleux, Arnaud Soler, Paul Crestani, Bruno Dehoux, Monique |
| Copyright Year | 2012 |
| Description | Journal: Critical Care Medicine |
| Abstract | Objectives: Fibroblast migration is an initiating step in fibroproliferation; its involvement during acute lung injury and acute respiratory distress syndrome remains poorly understood. The aims of this study were: 1) to determine whether bronchoalveolar lavage fluids from patients with acute lung injury/acute respiratory distress syndrome modulate lung fibroblast migration; 2) to assess lung fibroblast migration’s clinical relevance; and 3) to evaluate the role of the platelet-derived growth factor pathway in this effect. Design: Prospective cohort study. Setting: Three intensive care units of a large tertiary referral center. Patients: 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). Interventions: After bronchoalveolar lavage fluids collection during standard care, the patients were followed up for 28 days 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. Measurements and Main Results: 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. Conclusions: Together, our 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. |
| Related Links | http://pdfs.semanticscholar.org/d513/721c2bc31c58a1ab4bc17886adbc54aac727.pdf https://core.ac.uk/download/pdf/52413527.pdf |
| Ending Page | 2049 |
| Page Count | 9 |
| Starting Page | 2041 |
| ISSN | 00903493 |
| e-ISSN | 15300293 |
| DOI | 10.1097/ccm.0b013e31824e65ba |
| Journal | Critical Care Medicine |
| Issue Number | 7 |
| Volume Number | 40 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2012-07-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Critical Care Medicine Acute Respiratory Distress Syndrome Bronchoalveolar Lavage Fluid Platelet-derived Growth Factor |
| Content Type | Text |
| Resource Type | Article |
| Subject | Critical Care and Intensive Care Medicine |
