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Biting the FLIPR that Feeds

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Science Translational Medicine  12 Feb 2014:
Vol. 6, Issue 223, pp. 223ec30
DOI: 10.1126/scitranslmed.3008645

Platelets are best known for their ability to sense endothelial injury, become tethered to other platelets and clotting proteins, and to then form a thrombus. However, platelets are increasingly recognized to also have proinflammatory properties. For instance, platelets and their microparticles have been shown to bind to immune cells, leading to immune activation.

Now, Tersteeg and colleagues study in detail the morphological changes that occur subsequent to platelet activation using human blood cells in a flow chamber in order to approximate arterial shear forces. They find that platelets form long (~250 μm), thin filamentous flow-induced protrusions (FLIPRs) that extend downstream. The generation of FLIPRs is an active process requiring calcium signaling and the activation of the small guanosine triphosphatase Rac1. The authors investigated the role of FLIPRs for immune activation. With microscopy, both monocytes and neutrophils are captured by FLIPRs and roll on them in a P-selectin–dependent manner. These cells also retain platelet microparticles and express activation markers, suggesting that this interaction with FLIPRs leads to immune activation. Last, the authors demonstrate that FLIPRs are generated after arterial injury in mice in vivo, suggesting that these observations are of physiological importance.

The cross-talk between thrombosis and inflammation is complex and bidirectional. These new data suggest that platelets go to great lengths to mediate inflammation. In some circumstances, this is likely a protective process, but it is reasonable to speculate that modulating this nexus between endothelial cell activation, thrombosis, and immune activation could result in new adjunct therapies for treating cardiovascular disease and cancer.

C. Tersteeg et al., FLow-Induced PRotrusions (FLIPRs): A platelet-derived platform for the retrieval of microparticles by monocytes and neutrophils. Circ. Res., published online 9 January 2014 (10.1161/CIRCRESAHA.114.302361). [Abstract]

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