期刊
JOURNAL OF CELL BIOLOGY
卷 154, 期 3, 页码 485-490出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200105058
关键词
adhesion; cytokines; integrins; platelets; translation
类别
资金
- NHLBI NIH HHS [R01 HL044525, P50 HL50153, HL56713, R37 HL044525, HL44525] Funding Source: Medline
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 1 beta precursor (pro-IL-1 beta). Unexpectedly, the mRNA for IL-1 beta 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-1 beta protein, a response that is abolished by translational inhibitors A portion of the IL-1 beta 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 beta (3) integrin engagement markedly attenuated the synthesis of IL-1 beta, identifying a new link between the coagulation and inflammatory cascades, and suggesting that antithrombotic therapies may also have novel antiinflammatory effects.
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