Activated platelets mediate inflammatory signaling by regulated interleukin 1β synthesis

By S. Lindemann, N. Tolley, D. Dixon, T. McIntyre, S. Prescott, G. Zimmerman, A. Weyrich. Journal of Cell Biology, 2001

771 citations recorded by the source corpus.

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.

Subfields: Hematology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/c113c7cf76292e69d5eda218c1cca3e98b9e0421

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Citations in the corpus

A Critical Role of Platelet Adhesion in the Initiation of Atherosclerotic Lesion Formation (2002, background): “Previously, two cytokines, CD40L and IL-1 , have been identified in platelets that alter the chemotactic and adhesive properties of endothelium by enhancing endothelial surface expression of adhesion receptors including VCAM-1 as well as the release of chemokines such as MCP-1 (7, 9, 10).”
Platelet activation in obese women: role of inflammation and oxidant stress. (2002, neutral): “Fasting insulin, μU/mL 10 (8-12) 10 (8-17) 27 (24-42) H = 56.”
Understanding the mechanism of IL-1β secretion (2011, background): “This was originally observed in P2X7-receptorstimulated LPS-treated THP-1 cells [41], and thrombin activated platelets [42].”
Autologous platelets as a source of proteins for healing and tissue regeneration (2003, background): “As well as possessing classical pathways of granule secretion and eicosanoid generation, platelets have recently been shown, somewhat surprisingly for anucleate cells, to contain mRNA for interleukin 1β precursor (102).”
Cytokines in atherosclerosis: pathogenic and regulatory pathways. (2006, background): “While IL-1 cannot be detected in resting platelets, it is shed in its active form in microvesicles, after activation with thrombin (402).”
Escaping the nuclear confines: signal-dependent pre-mRNA splicing in anucleate platelets. (2005, methodology): “The photomicrographs in this figure are representative of three independent experiments. repressed until the cells are appropriately stimulated (Lindemann et al., 2001a).”
Platelets in Inflammation and Atherogenesis (2015, background): “Platelets within the atherosclerotic plaque may remain activated for a long time providing for proinflammatory IL-1β production [(111), see also Figure 3].”
Platelets and the immune continuum (2011, background): “In addition, when platelets adhere to inflamed atherosclerotic endothelium and become activated they secrete pro-inflammatory mediators, including CD154, IL-1β and CCL5 (also known as RANTES), which promote activation of the endothelium and enhance monocyte recruitmen”