Activated platelets mediate inflammatory signaling by regulated interleukin 1β synthesis (original) (raw)
Report| August 06 2001
4Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112
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4Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112
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2Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112
4Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112
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1Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112
3Department of Pathology, University of Utah, Salt Lake City, UT 84112
4Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112
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1Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112
5Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112
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1Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112
4Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112
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1Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112
4Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112
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Stephan Lindemann
4Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112
Neal D. Tolley
4Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112
Dan A. Dixon
2Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112
4Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112
Thomas M. McIntyre
1Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112
3Department of Pathology, University of Utah, Salt Lake City, UT 84112
4Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112
Stephen M. Prescott
1Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112
5Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112
Guy A. Zimmerman
1Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112
4Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112
Andrew S. Weyrich
1Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112
4Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, UT 84112
Address correspondence to Andrew S. Weyrich, Program in Human Molecular Biology and Genetics, University of Utah, 15 North 2030 East, Bldg. 533, Rm. 4220, Salt Lake City, UT 84112. Tel.: (801) 585-0702. Fax: (801) 585-0701. E-mail: [email protected]
The online version of this article contains supplemental material.
Abbreviations used in this paper: COX, cyclooxygenase; GAPDH, glutaraldehyde 3-phosphate dehydrogenase; IL, interleukin; M-CSF, macrophage colony stimulating factor; PAF, platelet-activating factor; PMN, polymorphonuclear leukocyte; pro–IL-1β, IL-1β precursor.
Received: May 10 2001
Revision Received: June 22 2001
Accepted: June 25 2001
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2001
J Cell Biol (2001) 154 (3): 485–490.
Platelets release preformed mediators and generate eicosanoids that regulate acute hemostasis and inflammation, but these anucleate cytoplasts are not thought to synthesize proteins or cytokines, or to influence inflammatory responses over time. Interrogation of an arrayed cDNA library demonstrated that quiescent platelets contain many messenger RNAs, one of which codes for interleukin 1β precursor (pro–IL-1β). Unexpectedly, the mRNA for IL-1β and many other transcripts are constitutively present in polysomes, providing a mechanism for rapid synthesis. Platelet activation induces rapid and sustained synthesis of pro–IL-1β protein, a response that is abolished by translational inhibitors. A portion of the IL-1β is shed in its mature form in membrane microvesicles, and induces adhesiveness of human endothelial cells for neutrophils. Signal-dependent synthesis of an active cytokine over several hours indicates that platelets may have previously unrecognized roles in inflammation and vascular injury. Inhibition of β3 integrin engagement markedly attenuated the synthesis of IL-1β, identifying a new link between the coagulation and inflammatory cascades, and suggesting that antithrombotic therapies may also have novel antiinflammatory effects.
The Rockefeller University Press
2001
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