Blood rheology, cell adhesion and endothelial activation

描述（由申请人提供）： 红细胞（RBC）通过其赋予血液的独特悬浮流变学在白细胞-内皮（L-E）相互作用中发挥重要作用。例如，我们以前发现，当流动室中细胞悬浮液的血细胞比容从0增加到30%时，结合的白细胞数量增加了10倍。在红细胞存在下细胞粘附的这种增强是由于流动的淋巴细胞和红细胞之间的物理而非生物化学相互作用。在这项资助的前3年，我们已经展示了血细胞之间的机械相互作用如何促进白细胞滚动和粘附。我们已经，第一次，估计流体动力施加在流动的血液，影响细胞，因为它们进入毛细血管后微静脉和滚动的内皮。这些研究，在相关的几何形状进行，提供了一个更好的理解白细胞滚动的机制，并表明，血管几何形状和红细胞的组织在毛细血管后微静脉白细胞滚动中发挥重要作用。如在原始申请中所提出的，我们已经证明存在将WBC驱动到壁所需的RBC的最佳配置。在这一竞争性更新中，我们通过检查体内各种组织中的白细胞滚动来扩展这些研究，以研究血管形状和红细胞聚集在白细胞滚动启动中的作用。数学建模和新型微加工网络将用于确定白细胞粘附所需的临界流体动力学和血管参数。在这次更新中，我们还扩大了研究范围，以研究流动的红细胞和白色血细胞对血管生物学和动脉粥样硬化病变形成的影响。与以前的工作相反，我们的方法隐含了血液的颗粒性质，因此更准确地再现了弯曲和分支血管中施加的力。将使用体内实验和数学建模的组合来评估导致动脉粥样硬化病变的流体力和血管几何形状的组合。

DESCRIPTION (provided by applicant): Red blood cells (RBCs) play an important role in leukocyte-endothelial (L-E) interactions through the unique suspension theology that they impart to blood. For example, we previously found a 10-fold increase in the number of bound leukocytes when the hematocrit of the cell suspension in a flow chamber was increased from 0 to 30%. This enhancement of cell adhesion in the presence of RBCs was due to physical, rather than biochemical, interactions between the flowing lymphocytes and RBCs. In the first 3 years of this grant, we have shown how mechanical interactions between blood cells contribute to leukocyte rolling and adhesion. We have, for the first time, estimated the hydrodynamic forces exerted in flowing blood that influence cells as they enter postcapillary venules and roll on the endothelium. These studies, performed in relevant geometries, provide a better understanding of the mechanism of leukocyte rolling, and show that vessel geometry and RBC organization play important roles in leukocyte rolling in postcapillary venules. As proposed in the original application, we have demonstrated that there is an optimal configuration of RBCs required to drive the WBC to the wall. In this competing renewal, we extend these studies to investigate the role of blood vessel shape and RBC aggregation in the initiation of leukocyte rolling by examining leukocyte rolling in various tissues in vivo. Mathematical modeling and novel microfabricated networks will be used to determine the critical fluid dynamics and vessel parameters required for leukocyte adhesion. In this renewal, we also expand the scope to study the influence of flowing red and white blood cells on vascular biology and the formation of atherosclerotic lesions. As opposed to previous work, our approach includes implicitly the particulate nature of blood, and therefore more accurately reproduces the forces exerted in curved and branched vessels. A combination of in vivo experiments and mathematical modeling will be used to assess the combination of fluid forces and vessel geometries that lead to atherosclerotic lesions.