Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

PNAS 101 (18): 7076-7081

Copyright © 2004 by the National Academy of Sciences.


Medical Sciences

Neutrophils alter the inflammatory milieu by signal-dependent translation of constitutive messenger RNAs

Stephan W. Lindemann * {dagger}, Christian C. Yost * {ddagger}, Melvin M. Denis *, Thomas M. McIntyre * § ¶, Andrew S. Weyrich * §, and Guy A. Zimmerman * § ||

*Program in Human Molecular Biology and Genetics and Departments of §Internal Medicine, Pathology, and {ddagger}Pediatrics, University of Utah, 15 North, 20230 East, Building 533, Room 4220, Salt Lake City, UT 84112

Communicated by Raymond L. White, University of California at San Francisco, Emeryville, CA, March 22, 2004

Received for publication January 25, 2004.

Abstract: The mechanisms by which neutrophils, key effector cells of the innate immune system, express new gene products in inflammation are largely uncharacterized. We found that they rapidly translate constitutive mRNAs when activated, a previously unrecognized response. One of the proteins synthesized without a requirement for transcription is the soluble IL-6 receptor {alpha}, which translocates to endothelial cells and induces a temporal switch to mononuclear leukocyte recruitment. Its synthesis is regulated by a specialized translational control pathway that is inhibited by rapamycin, a bacterial macrolide with therapeutic efficacy in transplantation, inflammatory syndromes, and neoplasia. Signal-dependent translation in activated neutrophils may be a critical mechanism for alteration of the inflammatory milieu and a therapeutic target.


Abbreviations: PMNs, polymorphonuclear leukocytes; mTOR, mammalian target of rapamycin; IL-6R{alpha}, IL-6 receptor {alpha} subunit; PAF, platelet-activating factor; HUVEC, human umbilical vein endothelial cell; LPS, lipopolysaccharide; fMLP, N-formylmethionylleucylphenylalanine; EC, endothelial cells.

{dagger} Present address: Department of Medicine II, Johannes Gutenberg University, 55101 Mainz, Germany.

|| To whom correspondence should be addressed. E-mail: guy.zimmerman{at}hmbg.utah.edu.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Platelets as Cellular Effectors of Inflammation in Vascular Diseases.
M. T. Rondina, A. S. Weyrich, and G. A. Zimmerman (2013)
Circ. Res. 112, 1506-1519
   Abstract »    Full Text »    PDF »
The role of Interleukin 6 in the pathophysiology of rheumatoid arthritis.
S. Srirangan and E. H. Choy (2010)
Therapeutic Advances in Musculoskeletal Diseases 2, 247-256
   Abstract »    PDF »
Translation Control: A Multifaceted Regulator of Inflammatory Response.
B. Mazumder, X. Li, and S. Barik (2010)
J. Immunol. 184, 3311-3319
   Abstract »    Full Text »    PDF »
Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor.
J.-M. Dayer and E. Choy (2010)
Rheumatology 49, 15-24
   Abstract »    Full Text »    PDF »
Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates.
C. C. Yost, M. J. Cody, E. S. Harris, N. L. Thornton, A. M. McInturff, M. L. Martinez, N. B. Chandler, C. K. Rodesch, K. H. Albertine, C. A. Petti, et al. (2009)
Blood 113, 6419-6427
   Abstract »    Full Text »    PDF »
Cyclooxygenase-2 Induced by Zymosan in Human Monocyte-Derived Dendritic Cells Shows High Stability, and Its Expression Is Enhanced by Atorvastatin.
Y. Alvarez, C. Municio, S. Alonso, J. A. S. Roman, M. S. Crespo, and N. Fernandez (2009)
J. Pharmacol. Exp. Ther. 329, 987-994
   Abstract »    Full Text »    PDF »
The PI3K/Akt/mTOR pathway in innate immune cells: emerging therapeutic applications.
T Weichhart and M D Saemann (2008)
Ann Rheum Dis 67, iii70-iii74
   Abstract »    Full Text »    PDF »
Signal-Dependent Protein Synthesis by Activated Platelets: New Pathways to Altered Phenotype and Function.
G. A. Zimmerman and A. S. Weyrich (2008)
Arterioscler Thromb Vasc Biol 28, s17-s24
   Abstract »    Full Text »    PDF »
Mouse neutrophilic granulocytes express mRNA encoding the macrophage colony-stimulating factor receptor (CSF-1R) as well as many other macrophage-specific transcripts and can transdifferentiate into macrophages in vitro in response to CSF-1.
R. T. Sasmono, A. Ehrnsperger, S. L. Cronau, T. Ravasi, R. Kandane, M. J. Hickey, A. D. Cook, S. R. Himes, J. A. Hamilton, and D. A. Hume (2007)
J. Leukoc. Biol. 82, 111-123
   Abstract »    Full Text »    PDF »
Isolation of polysome-bound mRNA from solid tissues amenable for RT-PCR and profiling experiments.
M. J. Del Prete, R. Vernal, H. Dolznig, E. W. Mullner, and J. A. Garcia-Sanz (2007)
RNA 13, 414-421
   Abstract »    Full Text »    PDF »
mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated human platelets.
A. S. Weyrich, M. M. Denis, H. Schwertz, N. D. Tolley, J. Foulks, E. Spencer, L. W. Kraiss, K. H. Albertine, T. M. McIntyre, and G. A. Zimmerman (2007)
Blood 109, 1975-1983
   Abstract »    Full Text »    PDF »
Dual role for RhoA in suppression and induction of cytokines in the human neutrophil.
M. B. Fessler, P. G. Arndt, I. Just, J. A. Nick, K. C. Malcolm, and G. Scott Worthen (2007)
Blood 109, 1248-1256
   Abstract »    Full Text »    PDF »
Neutrophils and keratinocytes in innate immunity--cooperative actions to provide antimicrobial defense at the right time and place.
N. Borregaard, K. Theilgaard-Monch, J. B. Cowland, M. Stahle, and O. E. Sorensen (2005)
J. Leukoc. Biol. 77, 439-443
   Abstract »    Full Text »    PDF »
Activated Polymorphonuclear Leukocytes Rapidly Synthesize Retinoic Acid Receptor-{alpha}: A Mechanism for Translational Control of Transcriptional Events.
C. C. Yost, M. M. Denis, S. Lindemann, F. J. Rubner, G. K. Marathe, M. Buerke, T. M. McIntyre, A. S. Weyrich, and G. A. Zimmerman (2004)
J. Exp. Med. 200, 671-680
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882