Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Circulating Thioredoxin Suppresses Lipopolysaccharide-Induced Neutrophil Chemotaxis

Hajime Nakamura, Leonore A. Herzenberg, Jie Bai, Shinichi Araya, Norihiko Kondo, Yumiko Nishinaka, Leonard A. Herzenberg and Junji Yodoi
Proceedings of the National Academy of Sciences of the United States of America
Vol. 98, No. 26 (Dec. 18, 2001), pp. 15143-15148
Stable URL: http://www.jstor.org/stable/3057424
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Circulating Thioredoxin Suppresses Lipopolysaccharide-Induced Neutrophil Chemotaxis
Preview not available

Abstract

Thioredoxin (Trx), a redox enzyme with a conserved active site (Cys-32-Gly-Pro-Cys-35), is induced and secreted into circulation in response to inflammation. Studies here demonstrate that elevating Trx levels in circulation either by i.v. injection of recombinant Trx or stimulating Trx release in Trx-transgenic mice dramatically blocks lipopolysaccharide (LPS)-stimulated neutrophil migration in the murine air pouch chemotaxis model. Furthermore, we show that leukocyte recruitment induced by the murine chemokines KC/GROα, RANTES (regulated upon activation, normal T cell expressed and secreted), and monocyte chemoattractant protein-1 (MCP-1) is suppressed also in Trx-transgenic mice. Addressing the mechanism responsible for this suppression, we show that circulating Trx blocks (i) the LPS-stimulated in vitro activation of neutrophil p38 mitogen-activated protein kinase, (ii) the normal down-regulation of CD62L on neutrophils migrating into the LPS-stimulated air pouch, and (iii) the in vitro adhesion of LPS-activated neutrophils on endothelial cells. However, as we also show, Trx does not alter the expression of endothelial cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, CD62P, and CD62E) within 3 h. Collectively, these findings indicate that elevated levels of circulating Trx interfere with chemotaxis by acting directly on neutrophils. We discuss these findings in the context of recent studies reporting beneficial effects of acutely elevated Trx in ischemic injury and negative effects associated with chronically elevated Trx in HIV disease.

Page Thumbnails

  • Thumbnail: Page 
15143
    15143
  • Thumbnail: Page 
15144
    15144
  • Thumbnail: Page 
15145
    15145
  • Thumbnail: Page 
15146
    15146
  • Thumbnail: Page 
15147
    15147
  • Thumbnail: Page 
15148
    15148