Alveolar fibroblasts in acute lung injury: biological behaviour and clinical relevance

Eur Respir J. 2010 Jun;35(6):1312-21. doi: 10.1183/09031936.00074709. Epub 2009 Oct 19.

Abstract

Although fibroblasts are key cells in the lung repair/fibrosis process, their characteristics are poorly studied in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The aims of our study were to: 1) determine the biological behaviour of alveolar fibroblasts during ALI; and 2) to evaluate the clinical relevance of positive alveolar fibroblast culture from patients with ALI/ARDS. Cells were cultured from bronchoalveolar lavage (BAL) obtained from 68 critically ill, ventilated patients: ALI n = 17; ARDS n = 31; and ventilated controls n = 20. Patients were followed for 28 days and clinical data was recorded. We studied proliferation, migration and collagen-1 synthesis capacities of fibroblasts. Cells expressing fibroblast markers were cultured from BAL obtained in six (35%) ALI patients and six (19%) ARDS patients, but never from ventilated controls. Alveolar fibroblasts exhibited a persistent activated phenotype with enhanced migratory and collagen-1 production capacities, with hyporesponsiveness to prostaglandin E(2) compared to normal lung fibroblasts (p< or =0.04). Positive fibroblast culture was associated with both an increased collagen-1 concentration and monocyte/macrophage percentage in BAL fluid (p< or =0.01), and with a reduced duration of mechanical ventilation (p<0.001). We conclude that activated alveolar fibroblasts can be cultured either in ALI or ARDS and that their presence might reflect the initiation of the organising phase of ALI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / pathology*
  • Acute Lung Injury / physiopathology
  • Adult
  • Aged
  • Biomarkers / metabolism
  • Bronchoalveolar Lavage Fluid / cytology*
  • Cell Division / physiology
  • Cell Movement / physiology
  • Cells, Cultured
  • Chemokine CCL2 / metabolism
  • Collagen Type I / metabolism
  • Female
  • Fetal Proteins / metabolism
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Humans
  • Interleukin-8 / metabolism
  • Male
  • Middle Aged
  • Peptide Fragments
  • Procollagen
  • Pulmonary Alveoli / pathology*
  • Respiratory Distress Syndrome / pathology*
  • Respiratory Distress Syndrome / physiopathology
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Biomarkers
  • CCL2 protein, human
  • Chemokine CCL2
  • Collagen Type I
  • Fetal Proteins
  • Interleukin-8
  • Peptide Fragments
  • Procollagen
  • Transforming Growth Factor beta1
  • procollagen Type I N-terminal peptide