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Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, OH 44195
Platelets express TLR4 receptors, but its ligand LPS does not directly activate thrombotic functions nor, obviously, transcription by these anucleate cells. Platelets, however, store information that changes their phenotype over a few hours in the form of unprocessed RNA transcripts. We show even low concentrations of LPS in the presence of soluble CD14 initiated splicing of unprocessed IL-1β RNA, with translation and accumulation of IL-1β protein. LPS was a more robust agonist for this response than thrombin. Platelets also contained cyclooxygenase-2 pre-mRNA, which also was spliced and translated after LPS stimulation. Flow cytometry and immunocytochemistry of platelets extensively purified by negative immunodepletion showed platelets contained IL-1β, and quantitative assessment of white blood cell contamination by CD14 real time PCR confirms that leukocytes were not the IL-1β source, nor were they required for platelet stimulation. LPS did not initiate rapid platelet responses, but over time did prime platelet aggregation to soluble agonists, induced actin rearrangement, and initiated granule secretion with P-selectin expression that resulted the coating of quiescent leukocytes with activated platelets. LPS is a direct agonist for platelets that allows these cells to directly participate in the innate immune response to bacteria.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grant P50 HL081011.
2 Address correspondence and reprint requests to Dr. Thomas M. McIntyre, Department of Cell Biology, NE-10, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine, 9500 Euclid Avenue, Cleveland, OH 44195. E-mail address: mcintyt{at}ccf.org
3 Abbreviations used in this paper: LBP, LPS-binding protein; DAPI, 4',6'- diamidino-2-phenylindole.
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