Bronchoalveolar lavage fluid from patients with acute lung injury/acute respiratory distress syndrome induces myofibroblast differentiation

Lauren Synenki*, Navdeep S. Chandel, G. R.Scott Budinger, Helen K. Donnelly, Jeremy Topin, James Eisenbart, Borko Jovanovic, Manu Jain

*Corresponding author for this work

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

OBJECTIVE: Myofibroblasts express α-smooth muscle actin (αSMA), are important in tissue repair, and are present in the early phase of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). We wished to determine whether bronchoalveolar lavage fluid (BALF) from ALI/ARDS patients can induce myofibroblast differentiation and if this induction is associated with outcome. DESIGN: A single-center cohort study enrolling patients between 2002 and 2005. SETTING: Medical intensive care unit of a tertiary care medical center. PATIENTS: Adult patients meeting the American-European Consensus Conference definition of ALI/ARDS. INTERVENTIONS: BALF was collected from ALI/ARDS patients within 48 hrs of intubation and incubated with normal human lung fibroblasts in vitro, and αSMA expression was assessed by reverse transcription polymerase chain reaction. BALF was also collected and tested from negative control patients. ALI/ARDS patients were followed for 28 days or death. MEASUREMENTS AND MAIN RESULTS: Thirty-one lung injury and 11 negative control patients were enrolled from 2002 to 2005. ALI/ARDS BALF demonstrated potent αSMA induction with a mean value 92% greater than negative controls (34.5% ± 7.6% vs. 18% ± 2.4% of maximal transforming growth factor [TGF]-β1 [5 ng/mL], p < .02). The specific TGF-β1 receptor inhibitor SB431542 reduced ALI/ARDS BALF-stimulated αSMA induction by 52% (p < .005). There was no correlation between ALI/ARDS BALF-induced αSMA and procollagen 3 induction (r = -.08, p = .66). The odds ratio for survival was 6.75 (1.15-39.80) times higher for ALI/ARDS patients with αSMA induction between 15% and 75% of maximal TGF-β1 induction (5 ng/mL) than outside this range. CONCLUSIONS: ALI/ARDS BALF-induced myofibroblast differentiation is partially attributable to TGF-β1. Procollagen 3 and αSMA are regulated by distinct mechanisms in ALI/ARDS and there may be an optimal level of myofibroblast induction that is associated with better outcome.

Original languageEnglish (US)
Pages (from-to)842-848
Number of pages7
JournalCritical care medicine
Volume35
Issue number3
DOIs
StatePublished - Mar 1 2007

Keywords

  • Acute respiratory distress syndrome
  • Alpha-smooth muscle actin
  • Collagen 3
  • Repair
  • Transforming growth factor-β1

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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