Blood Rheology and Leukocyte Mechanics

描述(由申请人提供)： 循环细胞与血管壁之间的物理接触在免疫监测、转移和动脉粥样硬化中具有重要作用。但人们对黏附的白细胞和构成血容量最大的红细胞之间的机械相互作用知之甚少。我们最近发现，红细胞(RBC)通过赋予血液独特的悬浮流变学特性，在体外和体内的白细胞-内皮(L-E)相互作用中发挥着重要作用。我们发现，当流室中细胞悬浮液的红细胞压积从0增加到30%时，结合的白细胞数量增加了10倍。我们还发现，在红细胞存在的情况下，这种细胞黏附的增强是由于黏附的淋巴细胞和红细胞之间的物理作用，而不是化学作用。 尽管红细胞在血小板沉积到血管壁上的作用已经得到了广泛的研究，但对于红细胞在促进L-E相互作用中的作用还很少受到关注。这项拟议的研究将采用实验和理论两种方法量化导致L-E血流相互作用增强的物理力和流变参数。流动室研究将在平行平板流动室中进行，这是一种允许在细胞流经矩形流动室时精确控制流量和溶液流变性的装置。 理论研究将采用格子-玻尔兹曼方法，这是我们最近在血液流变学和颗粒相互作用领域采用的一种新方法。实验和理论方法的独特结合将构成我独立科学生涯的基础。

DESCRIPTION (provided by applicant): Physical contact between circulating cells and the vessel wall is of central importance in immune surveillance, metastasis and atherosclerosis. But little is known about the mechanical interactions between adhering leukocytes and the red blood cells that constitute most of the blood volume. We have recently discovered that red blood cells (RBCs) play an important role in leukocyte-endothelial (L-E) interactions, both in vitro and in vivo through the unique suspension rheology characteristics that they impart to blood. We 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%. We have also discovered that this enhancement of cell adhesion in the presence of RBCs is due to physical, rather than chemical interactions between the adherent lymphocytes and RBCs. Although the role of RBCs in platelet deposition onto the vessel wall has been studied extensively, little attention has been given to the role of RBCs in promoting L-E interactions. The proposed study will quantify the physical forces and rheological parameters that cause enhanced L-E interactions in blood flow using both experimental and theoretical approaches. Flow chamber studies will be carried out in the parallel plate flow chamber, a device that allows precise control over flow rates and solution rheology as cells flow through a rectangular chamber. Theoretical studies will employ the Lattice-Boltzmann method, a novel approach we recently adapted to the field of blood rheology and particle interactions. The unique combination of experimental and theoretical approaches will form the basis of my independent scientific career.