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Extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide.

Publication ,  Journal Article
Miller, DL; Welty-Wolf, K; Carraway, MS; Ezban, M; Ghio, A; Suliman, H; Piantadosi, CA
Published in: Am J Respir Cell Mol Biol
June 2002

Initiation of coagulation by tissue factor (TF) is a potentially powerful regulator of local inflammatory responses. We hypothesized that blockade of TF-factor VIIa (FVIIa) complex would decrease lung inflammation and proinflammatory cytokine release after tracheal instillation of Escherichia coli lipopolysaccharide (LPS 0111:B4). At the time of injury, rats received one dose of site-inactivated FVIIa (FFR-FVIIa) or saline intravenously. At 0, 6,12, 24, and 48 h after injury, lungs were examined for histologic changes and bronchoalveolar lavage (BAL) was performed to assess protein, lactate dehydrogenase (LDH) activity, cell counts, and cytokine levels. LPS-injured rats treated with FFR-FVIIa showed decreased intra-alveolar inflammation and fibrin deposition by light microscopy compared with untreated rats. This was accompanied by decreased protein leakage (P < 0.0001), LDH activity (P < 0.0001), and local elaboration of interleukin (IL)-1beta, IL-6, and IL-10 (all P < 0.0001), but not tumor necrosis factor (TNF)-alpha. Protection was associated with reduction of TF mRNA expression in whole lung, but not with changes in nuclear translocation of nuclear factor (NF)-kappaB. FFR-FVIIa given 6 h after LPS afforded equivalent lung protection. Therefore, blockade of TF-FVIIa complex protects the lung from injury by LPS in part by reducing local expression of proinflammatory cytokines and may offer promise for therapy of acute lung injury.

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Published In

Am J Respir Cell Mol Biol

DOI

ISSN

1044-1549

Publication Date

June 2002

Volume

26

Issue

6

Start / End Page

650 / 658

Location

United States

Related Subject Headings

  • Trachea
  • Thromboplastin
  • Thrombin
  • Reverse Transcriptase Polymerase Chain Reaction
  • Respiratory System
  • Rats, Sprague-Dawley
  • Rats
  • Prothrombin
  • Protein Transport
  • NF-kappa B
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Miller, D. L., Welty-Wolf, K., Carraway, M. S., Ezban, M., Ghio, A., Suliman, H., & Piantadosi, C. A. (2002). Extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide. Am J Respir Cell Mol Biol, 26(6), 650–658. https://doi.org/10.1165/ajrcmb.26.6.4688
Miller, Debra L., Karen Welty-Wolf, Martha Sue Carraway, Mirella Ezban, Andrew Ghio, Hagir Suliman, and Claude A. Piantadosi. “Extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide.Am J Respir Cell Mol Biol 26, no. 6 (June 2002): 650–58. https://doi.org/10.1165/ajrcmb.26.6.4688.
Miller DL, Welty-Wolf K, Carraway MS, Ezban M, Ghio A, Suliman H, et al. Extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide. Am J Respir Cell Mol Biol. 2002 Jun;26(6):650–8.
Miller, Debra L., et al. “Extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide.Am J Respir Cell Mol Biol, vol. 26, no. 6, June 2002, pp. 650–58. Pubmed, doi:10.1165/ajrcmb.26.6.4688.
Miller DL, Welty-Wolf K, Carraway MS, Ezban M, Ghio A, Suliman H, Piantadosi CA. Extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide. Am J Respir Cell Mol Biol. 2002 Jun;26(6):650–658.

Published In

Am J Respir Cell Mol Biol

DOI

ISSN

1044-1549

Publication Date

June 2002

Volume

26

Issue

6

Start / End Page

650 / 658

Location

United States

Related Subject Headings

  • Trachea
  • Thromboplastin
  • Thrombin
  • Reverse Transcriptase Polymerase Chain Reaction
  • Respiratory System
  • Rats, Sprague-Dawley
  • Rats
  • Prothrombin
  • Protein Transport
  • NF-kappa B