Alveolar fibroblasts in acute lung injury: biological behaviour and clinical relevance.
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.
Inserm Unité 700, Université Paris 7 Denis Diderot, 75018 Paris, France. christophe.quesnel@tnn.aphp.fr
C
C
Quesnel
L
L
Nardelli
P
P
Piednoir
V
V
Leçon
J
J
Marchal-Somme
S
S
Lasocki
L
L
Bouadma
I
I
Philip
P
P
Soler
B
B
Crestani
M
M
Dehoux
D055371:Acute Lung Injury / Q000473:pathology* / Q000503:physiopathology; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D005326:Fetal Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments; D011347:Procollagen; D011650:Pulmonary Alveoli / Q000473:pathology*; D012128:Respiratory Distress Syndrome / Q000473:pathology* / Q000503:physiopathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D024042:Collagen Type I; D005326:Fetal Proteins; D016209:Interleukin-8; D010446:Peptide Fragments; D011347:Procollagen; D053773:Transforming Growth Factor beta1; C047202:procollagen Type I N-terminal peptide