The alveolar epithelium can initiate the extrinsic coagulation cascade through expression of tissue factor

Julie A Bastarache; Ling Wang; Thomas Geiser; Zhengming Wang; Kurt H Albertine; Michael A Matthay; Lorraine B Ware

doi:10.1136/thx.2006.063305

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The alveolar epithelium can initiate the extrinsic coagulation cascade through expression of tissue factor

Journal article

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Peer reviewed

The alveolar epithelium can initiate the extrinsic coagulation cascade through expression of tissue factor

Julie A Bastarache, Ling Wang, Thomas Geiser, Zhengming Wang, Kurt H Albertine, Michael A Matthay and Lorraine B Ware

Thorax, Vol.62(7), pp.608-616

07/2007

DOI: 10.1136/thx.2006.063305

PMCID: PMC2117249

PMID: 17356058

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Abstract

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 α, interleukin 1β and interferon γ) 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.

acute lung injury

acute respiratory distress syndrome

ALI

ARDS

BAL

bronchoalveolar lavage

confidence threshold

MEM

minimal essential medium

phorbol myristate acetate

PMA

SAEC

small airway epithelial cells

tissue factor

Details

Title: Subtitle: The alveolar epithelium can initiate the extrinsic coagulation cascade through expression of tissue factor
Creators: Julie A Bastarache - Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, T1218 Medical Center North, Nashville, Tennessee 37232-2650, USA.
Ling Wang - Vanderbilt University
Thomas Geiser - University of Bern
Zhengming Wang - University of Utah
Kurt H Albertine - University of Utah
Michael A Matthay - University of California, San Francisco
Lorraine B Ware - Vanderbilt University
Resource Type: Journal article
Publication Details: Thorax, Vol.62(7), pp.608-616
DOI: 10.1136/thx.2006.063305
PMID: 17356058
PMCID: PMC2117249
NLM abbreviation: Thorax
ISSN: 0040-6376
eISSN: 1468-3296
Publisher: BMJ Publishing Group Ltd and British Thoracic Society
Language: English
Date published: 07/2007
Academic Unit: Orthopedics and Rehabilitation
Record Identifier: 9984304685502771

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