Active transforming growth factor-beta1 activates the procollagen I promoter in patients with acute lung injury.
OBJECTIVE
Fibroproliferation markers like procollagen I predict mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We sought to determine whether bronchoalveolar lavage fluid (BALF) from patients with lung injury contained mediators that would activate procollagen I promoter and if this activation predicted important clinical outcomes.


METHODS
Prospective controlled study of ALI/ARDS.


METHODS
Intensive care units and laboratory of a university hospital.


METHODS
Acute lung injury/ARDS, cardiogenic edema (negative controls) and pulmonary fibrosis (positive controls) patients.


METHODS
Bronchoalveolar lavage fluid was collected within 48 h of intubation from ALI/ARDS patients. BALF was also collected from patients with pulmonary fibrosis and cardiogenic pulmonary edema. Human lung fibroblasts were transfected with a procollagen I promoter-luciferase construct and incubated with BALF; procollagen I promoter activity was then measured. BALF active TGF-beta1 levels were measured by ELISA.


RESULTS
Twenty-nine ARDS patients, nine negative and six positive controls were enrolled. BALF from ARDS patients induced 41% greater procollagen I promoter activation than that from negative controls (p<0.05) and a TGF-beta1 blocking antibody significantly reduced this activation in ARDS patients. There was a trend toward higher TGF-beta1 levels in the ARDS group compared to negative controls (-1.056 log(10)+/-0.1415 vs -1.505 log(10)+/-0.1425) (p<0.09). Procollagen I promoter activation was not associated with mortality; however, lower TGF-beta1 levels were associated with more ventilator-free and ICU-free days.


CONCLUSIONS
Bronchoalveolar lavage fluid from ALI/ARDS patients activates procollagen I promoter, which is due partly to TGF-beta1. Activated TGF-beta1 may impact ARDS outcome independent of its effect on procollagen I activation.
Budinger
G R Scott
GR
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Medical School, 240 East Huron, Chicago, IL 60611, USA.
Chandel
Navdeep S
NS
Donnelly
Helen K
HK
Eisenbart
James
J
Oberoi
Monica
M
Jain
Manu
M
D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011347:Procollagen / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000145:classification / Q000378:metabolism* / Q000401:mortality; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053773:Transforming Growth Factor beta1
D011347:Procollagen; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1