Journal article
Intra-alveolar tissue factor pathway inhibitor is not sufficient to block tissue factor procoagulant activity
American journal of physiology. Lung cellular and molecular physiology, Vol.294(5), pp.L874-L881
05/01/2008
DOI: 10.1152/ajplung.00372.2007
PMCID: PMC2764534
PMID: 18310227
Abstract
The alveolar compartment in acute lung injury contains high levels of tissue factor (TF) procoagulant activity favoring fibrin deposition. We previously reported that the alveolar epithelium can release TF procoagulant activity in response to a proinflammatory stimulus. To test the hypothesis that the alveolar epithelium further modulates intra-alveolar fibrin deposition through secretion of an endogenous inhibitor to TF, tissue factor pathway inhibitor ( TFPI), we measured TFPI levels in edema fluid (EF) from patients with acute respiratory distress syndrome. To determine whether the alveolar epithelium can release TFPI, both full-length TFPI and truncated TFPI were measured ( ELISA) in pulmonary edema fluid from patients with acute respiratory distress syndrome ( ARDS) and a control group of patients with hydrostatic pulmonary edema ( HYDRO). TFPI protein was also measured in conditioned media ( CM) and cell lysates ( CL) from human alveolar epithelial cells (A549) after exposure to cytomix (TNF-alpha, IL-1 beta, IFN-gamma). TFPI protein levels were higher in pulmonary edema fluid from patients with ARDS vs. HYDRO. TFPI protein was increased in CM and did not change in CL after cytomix treatment; TFPI mRNA levels (RT-PCR) did not change. Despite the high levels of TFPI, both the EF and CM retained significant TF procoagulant activity as measured by plasma recalcification time. The majority of intra-alveolar TFPI was in a truncated, inactive form, whereas the majority of TFPI released from cells was full length, suggesting different mechanisms of inactivation. In summary, the alveolar epithelium releases TFPI in response to an inflammatory stimulus but does not increase TFPI gene transcription or protein production. Levels of intra-alveolar TFPI in ARDS are not sufficient to block intra-alveolar TF procoagulant activity due to truncation and inactivation of intra-alveolar TFPI.
Details
- Title: Subtitle
- Intra-alveolar tissue factor pathway inhibitor is not sufficient to block tissue factor procoagulant activity
- Creators
- Julie A. Bastarache - Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt Univ. School of Medicine, T 1218 Medical Center North, Nashville, TN 37232-2650, USA.Ling Wang - Vanderbilt UniversityZhengming Wang - University of UtahKurt H. Albertine - PEDIATRIC NEONATOLOGYMichael A. Matthay - University of California, San FranciscoLorraine B. Ware - Vanderbilt University
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Lung cellular and molecular physiology, Vol.294(5), pp.L874-L881
- DOI
- 10.1152/ajplung.00372.2007
- PMID
- 18310227
- PMCID
- PMC2764534
- NLM abbreviation
- Am J Physiol Lung Cell Mol Physiol
- ISSN
- 1040-0605
- eISSN
- 1522-1504
- Publisher
- Amer Physiological Soc
- Number of pages
- 8
- Grant note
- HL-081332; R37 HL051856; U01 HL081332; R37 HL051856-14; HL-51856; R01 HL051856 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R37HL051856 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 05/01/2008
- Academic Unit
- Orthopedics and Rehabilitation
- Record Identifier
- 9984304712502771
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