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.
Quesnel
C
C
Inserm Unité 700, Université Paris 7 Denis Diderot, 75018 Paris, France. christophe.quesnel@tnn.aphp.fr
Nardelli
L
L
Piednoir
P
P
Leçon
V
V
Marchal-Somme
J
J
Lasocki
S
S
Bouadma
L
L
Philip
I
I
Soler
P
P
Crestani
B
B
Dehoux
M
M
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