Platelets release preformed mediators and generate eicosanoids that regulat
e 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 fo
r interleukin 1 beta precursor (pro-IL-1 beta). Unexpectedly, the mRNA for
IL-1 beta and many other transcripts are constitutively present in polysome
s, providing a mechanism for rapid synthesis. Platelet activation induces r
apid and sustained synthesis of pro-IL-1 beta protein, a response that is a
bolished by translational inhibitors A portion of the IL-1 beta is shed in
its mature form in membrane microvesicles, and induces adhesiveness of huma
n endothelial cells for neutrophils. Signal-dependent synthesis of an activ
e 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, ide
ntifying a new link between the coagulation and inflammatory cascades, and
suggesting that antithrombotic therapies may also have novel antiinflammato
ry effects.