The alveolar epithelium can initiate the extrinsic coagulation cascade through expression of tissue factor.
BACKGROUND
The alveolar compartment is a procoagulant antifibrinolytic environment in acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). A study was undertaken to test the hypothesis that the alveolar epithelium can initiate intra-alveolar coagulation by expressing active tissue factor (TF).


METHODS
Using an in vitro cell surface TF assay and TF ELISA, the activity and production of TF in cultured alveolar epithelial (A549) cells following exposure to cytomix (tumour necrosis factor alpha, interleukin 1beta and interferon gamma) was measured. TF gene transcription was measured by semi-quantitative reverse-transcription PCR. Immunohistochemistry for TF was performed on lung sections from patients with ARDS and controls. TF protein levels were measured by ELISA in undiluted pulmonary oedema fluid from patients with ALI/ARDS and compared with control patients with hydrostatic pulmonary oedema.


RESULTS
TF activity, mRNA and protein levels increased in A549 cells after stimulation with cytomix. Increased TF activity was also seen in A549 cells following incubation with pulmonary oedema fluid from patients with ALI/ARDS. Immunohistochemistry for TF in human lung tissue from patients with ARDS showed prominent TF staining in alveolar epithelial cells as well as intra-alveolar macrophages and hyaline membranes. TF antigen levels in oedema fluid (median 37 113 (IQR 14 956-73 525) pg/ml) were significantly higher than in plasma (median 336 (IQR 165-669) pg/ml, p<0.001) in patients with ALI/ARDS, and TF procoagulant activity in oedema fluid was much higher than in plasma of these patients. Higher plasma levels were associated with mortality.


CONCLUSIONS
The alveolar epithelium is capable of modulating intra-alveolar coagulation through upregulation of TF following exposure to inflammatory stimuli and may contribute to intra-alveolar fibrin deposition in ARDS.
Bastarache
Julie A
JA
Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, T1218 Medical Center North, Nashville, Tennessee 37232-2650, USA. julie.bastarache@vanderbilt.edu
Wang
Ling
L
Geiser
Thomas
T
Wang
Zhengming
Z
Albertine
Kurt H
KH
Matthay
Michael A
MA
Ware
Lorraine B
LB
D001777:Blood Coagulation / Q000502:physiology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011654:Pulmonary Edema / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*
D012333:RNA, Messenger; D005337:Fibrin; D013925:Thromboplastin