PLATELET LEUKOCYTE PHYSIOLOGY IN CARDIOPULMONARY BYPASS

描述：(改编自调查人员摘要)心肺 搭桥手术深刻地改变了相互作用的凝血和免疫系统， 导致看似矛盾的凝血，血栓前状态， 免疫抑制和促炎疾病是导致 体外循环相关的肺和心肌损伤及出血 转流早期、高凝状态和免疫紊乱 后来在体外循环中。如前所述，在此 格兰特，体外循环导致动态改变 血小板-白细胞-红细胞-内皮细胞粘附性和功能性 相互作用，部分由末端膜组分的产生启动。 使用体内研究和体外全血模型和模拟 体外循环模型中，PI已经显示出抗原性和 循环中特异的β2整合素功能上调 体外循环中吞噬细胞、血小板α颗粒释放和 P-选择素的表达与循环中血小板的形成有关 -抗补体C5体外循环期间的白细胞结合物 单抗可阻断血小板和中性粒细胞的激活 模拟体外循环。进一步的研究表明， 网状红细胞促进活化的血小板微粒 形成时，认为血小板活化可能是C5b-9黏附时的结果 分子上调是C5a活性的结果。此外， 中性粒细胞释放和黏附上调是可分离的事件 网状血小板代表血小板亚群，这表明 不同的功能活动，并可能优先在 心肺转流术。本申请的目的是1)定义 补充性组件和其他调解器启动哪些参数 血小板白细胞内皮细胞活化2)分子定义 红细胞-血小板-白细胞相互作用的基础 凝血和炎症的细胞和可溶性介质 体外循环和确定内皮细胞的变化 由模拟体外循环诱导，使用添加到 当前型号。这些研究的长期目标是发展 减少体外循环并发症的治疗策略 循环和了解血小板-白血的基本生物学 细胞-甲状腺细胞-内皮细胞的相互作用。

DESCRIPTION: (Adapted from the investigator's abstract) Cardiopulmonary bypass profoundly alters the interacting coagulation and immune systems, resulting in seemingly contradictory coagulopathic, prothrombotic, immunosuppressive and proinflammatory diatheses that are responsible for cardiopulmonary bypass related pulmonary and myocardial injury and bleeding early during bypass and hypercoagulability and immunologic disturbances later in cardiopulmonary bypass. As demonstrated previously under this grant, cardiopulmonary bypass results in a dynamic alteration in platelet-leukocyte-erythrocyte-endothelial adhesive and functional interactions, in part initiated by terminal membrane component generation. Using in-vivo studies and in-vitro whole blood model and a simulated extracorporeal circulation model, the PI has shown that antigenic and functional upregulation of specific beta2 integrins occurs on circulating phagocytes in cardiopulmonary bypass, platelet alpha-granule release and P-selectin expression occurs with formation of circulating platelet -leukocyte conjugates during cardiopulmonary bypass at anti-complement C5 monoclonal antibody blocks both platelet and neutrophil activation during simulated extracorporeal circulation. Further work suggests that damaged and reticulated red blood cells promote activated platelet microparticle formation, that platelet activation may be a result of C5b-9 while adhesion molecule upregulation occurs a consequence of C5a activity. Furthermore, neutrophil granule release and adhesion upregulation are separable events and reticulated platelets represent a platelet subset which shows differential functional activity and may by preferentially lost during cardiopulmonary bypass. The aims of this application are to 1) define which complement components and other mediators initiate which parameters of platelet white blood cell endothelial activation 2) to define the molecular basis of erythrocyte-platelet-white blood cells interactions which generate cellular and soluble mediators of coagulation and inflammation in cardiopulmonary bypass and to define alterations in endothelial cells inducted by simulated extracorporeal circulation using an addition to the current model. The long term goals of these studies is to develop therapeutic strategies to alleviate complications of extracorporeal circulation and to understand the basic biology of platelet-white blood cell-erthyrocyte-endothelial interactions.