Mechanisms of platelet receptor regulation and disintegration (A07)

我们已经证明α ib β3及其相关的四联蛋白CD9可以不可逆地从循环血小板中去除。结扎的整合素被锚定后，聚集在血小板“后缘”，并在一个长突起或系索中分离，这一过程涉及机械力。我们发现明确的迹象表明，这种α ib β3/ cd9富集系链（称为PITTs）的流动依赖性沉积有助于血栓炎症。接下来，我们将重点研究PITT形成的详细分子基础和病理生理意义，以及其他血小板膜受体（如β1-整合素和GPVI）在体外和体内的“解体”/沉积。

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.