The Alveolar Epithelium can Initiate the Extrinsic Coagulation Cascade through Expression of Tissue Factor

Julie Bastarache ^1*, Ling Wang ¹, Thomas Geiser ², Zhenming Wang ³, Kurt Albertine ³, Michael Matthay ⁴ and Lorraine Ware ¹

¹ Vanderbilt University School of Medicine, United States
² University of Bern, United States
³ University of Utah, United States
⁴ University of California at San Francisco, United States

^* To whom correspondence should be addressed. E-mail: julie.bastarache{at}vanderbilt.edu.

Accepted 9 January 2007

Abstract

RATIONALE The alveolar compartment is a pro-coagulant, anti- fibrinolytic environment in acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS).

OBJECTIVES 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 we measured the activity and production of TF in cultured alveolar epithelial (A549) cells following exposure to cytomix (TNF-& [alpha], IL-1, IFN-). TF gene transcription was measured by semi-quantitative RT-PCR. Immunohistochemistry for TF was done on lung sections of ARDS patients compared to controls. TF protein levels were measured by ELISA in undiluted pulmonary edema fluid from ALI/ARDS patients compared to control patients with hydrostatic pulmonary edema.

MAIN RESULTS TF activity, mRNA and protein levels increased in A549 cells after stimulation with cytomix. In addition, increased TF activity was measured on A549 cells following incubation with pulmonary edema fluid from ALI/ARDS patients. Immunohistochemistry for TF in human lung tissue from ARDS patients showed prominent TF staining in alveolar epithelial cells as well as intra- alveolar macrophages and hyaline membranes. Additionally, TF antigen levels and TF procoagulant activity were very high in the pulmonary edema fluid of ALI/ARDS patients compared to plasma, and 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.

Keywords: Acute Lung Injury, Acute Respiratory Distress Syndrome, Extrinsic Coagulation Cascade, Fibrin Deposition, Hyaline Membranes

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Articles

AIRWAVES

Wisia Wedzicha
Thorax 2007 62: 561. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Bastarache, J. A., Fremont, R. D., Kropski, J. A., Bossert, F. R., Ware, L. B. (2009). Procoagulant alveolar microparticles in the lungs of patients with acute respiratory distress syndrome. Am. J. Physiol. Lung Cell. Mol. Physiol. 297: L1035-L1041 [Abstract] [Full Text]  
• Zimmerman, G. A. (2009). Thinking small, but with big league consequences: procoagulant microparticles in the alveolar space. Am. J. Physiol. Lung Cell. Mol. Physiol. 297: L1033-L1034 [Full Text]  
• Bastarache, J. A., Blackwell, T. S. (2009). Development of animal models for the acute respiratory distress syndrome. DMM 2: 218-223 [Abstract] [Full Text]  
• Mercer, P. F., Johns, R. H., Scotton, C. J., Krupiczojc, M. A., Konigshoff, M., Howell, D. C. J., McAnulty, R. J., Das, A., Thorley, A. J., Tetley, T. D., Eickelberg, O., Chambers, R. C. (2009). Pulmonary Epithelium Is a Prominent Source of Proteinase-activated Receptor-1-inducible CCL2 in Pulmonary Fibrosis. Am. J. Respir. Crit. Care Med. 179: 414-425 [Abstract] [Full Text]  
• Bastarache, J. A. (2009). The complex role of fibrin in acute lung injury. Am. J. Physiol. Lung Cell. Mol. Physiol. 296: L275-L276 [Full Text]  
• Schultz, M. J, Dixon, B., Levi, M. (2009). The pulmonary protein C system: preventive or therapeutic target in acute lung injury?. Thorax 64: 95-97 [Full Text]  
• Plotkowski, M. C., Feliciano, L. F. P., Machado, G. B. S., Cunha, L. G. Jr, Freitas, C., Saliba, A. M., de Assis, M. C. (2008). ExoU-induced procoagulant activity in Pseudomonas aeruginosa-infected airway cells. Eur Respir J 32: 1591-1598 [Abstract] [Full Text]  
• Shetty, S., Padijnayayveetil, J., Tucker, T., Stankowska, D., Idell, S. (2008). The fibrinolytic system and the regulation of lung epithelial cell proteolysis, signaling, and cellular viability. Am. J. Physiol. Lung Cell. Mol. Physiol. 295: L967-L975 [Abstract] [Full Text]  
• Bastarache, J. A., Wang, L., Wang, Z., Albertine, K. H., Matthay, M. A., Ware, L. B. (2008). Intra-alveolar tissue factor pathway inhibitor is not sufficient to block tissue factor procoagulant activity. Am. J. Physiol. Lung Cell. Mol. Physiol. 294: L874-L881 [Abstract] [Full Text]  
• Oeckler, R. A., Hubmayr, R. D. (2007). Ventilator-associated lung injury: a search for better therapeutic targets. Eur Respir J 30: 1216-1226 [Abstract] [Full Text]  
• Schultz, M. J, Levi, M. (2007). Pulmonary coagulopathy: a potential therapeutic target in different forms of lung injury. Thorax 62: 563-564 [Full Text]