Mechanisms of platelet receptor regulation and disintegration (A07)

我们已经证明，αIIbβ3及其相关的Tetraspanin CD9可以从循环中不可逆转地移除。这个过程涉及连接的整合素被锚定后的机械力，聚集在血小板的后缘，并在一个长的突起或系绳内分离。我们发现明显的迹象表明，这种αIIbCD3/β富集链(称为PITT)的血流依赖性沉积有助于血栓炎症。接下来，PITT形成的详细分子基础和病理生理学意义将是我们关注的焦点，以及其他血小板膜受体的‘崩解’/沉积，如β1-整合素和GPVI在体外和体内。

We have shown that αIIbβ3 together with its associated tetraspanin, CD9, can be irreversibly removed from circulating platelets. The process involves mechanical forces after the ligated integrin is anchored, clustered at the platelet ‘rear edge’ and segregated within a long protrusion or tether. We found clear indications that this flow-dependent deposition of αIIbβ3/CD9-enriched tethers (termed PITTs) contributes to thrombo-inflammation. Next, the detailed molecular basis and pathophysiological significance of PITT formation will be our focus as well as the ‘disintegration’/deposition of other platelet membrane receptors, such as β1-integrins and GPVI in vitro and in vivo.