Role of erythrocytes in leukocyte-endothelial interactions: Mathematical model and experimental validation
Role of erythrocytes in leukocyte-endothelial interactions: Mathematical model and experimental validation
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DOI：
10.1016/s0006-3495(96)79248-2
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发表时间：
1996-07-01
影响因子：
3.4
通讯作者：
Jain, RK
中科院分区：
文献类型：
--
作者：
Munn, LL;Melder, RJ;Jain, RK
循环细胞与血管壁的结合是炎症、转移和治疗性细胞递送的中心过程。先前的体外研究已经确定了在静态条件下控制该过程的各种循环细胞和内皮上的粘附分子。其他研究试图通过使贴壁细胞在体外与内皮细胞相互作用时受到剪切应力来模拟体内条件。这些实验通常用悬浮在牛顿溶液中的细胞进行。然而，由于血液的非牛顿流动，体内条件更加复杂，血液是由20- 40体积%的红细胞组成的悬浮液。由流动中的红细胞赋予的力可以有助于细胞粘附的过程。许多实验和理论研究表明，血液流变学可以通过增加白细胞上的法向力和轴向力或白细胞与血管壁碰撞的频率来影响循环白细胞的结合，但迄今为止还没有对这些现象进行系统的研究，本研究定量的红细胞（RBC）的细胞捕获和粘附的内皮细胞单层的数学建模和体外研究相结合的贡献。流动实验的数学建模表明，涉及REC诱导的白细胞分散和/或增加正常粘附接触的物理机制。在悬浮介质中有和没有红细胞的流动室研究表明，在壁碰撞和结合频率增加，并在红细胞的存在下，滚动速度下降。单独增加流体粘度不影响结合频率，并且差异不能归因于淋巴细胞的大的近壁过量。结果表明，红细胞有助于淋巴细胞向血管壁的运输和初始接合，通过添加红细胞作为该过程的重要贡献者来修改血管内皮的免疫细胞监视的现有范例。
The binding of circulating cells to the vascular wall is a central process in inflammation, metastasis, and therapeutic cell delivery. Previous in vitro studies have identified the adhesion molecules on various circulating cells and the endothelium that govern the process under static conditions. Other studies have attempted to simulate in vivo conditions by subjecting adherent cells to shear stress as they interact with the endothelial cells in vitro. These experiments are generally performed with the cells suspended in Newtonian solutions. However, in vivo conditions are more complex because of the non-Newtonian flow of blood, which is a suspension consisting of 20-40% erythrocytes by volume. The forces imparted by the erythrocytes in the flow can contribute to the process of cell adhesion. A number of experimental and theoretical studies have suggested that the rheology of blood can influence the binding of circulating leukocytes by increasing the normal and axial forces on leukocytes or the frequency of their collision with the vessel wall, but there have been no systematic investigations of these phenomena to date, The present study quantifies the contribution of red blood cells (RBCs) in cell capture and adhesion to endothelial monolayers using a combination of mathematical modeling and in vitro studies. Mathematical modeling of the flow experiments suggested a physical mechanism involving REC-induced leukocyte dispersion and/or increased normal adhesive contact. Flow chamber studies performed with and without RBCs in the suspending medium showed increases in wall collision and binding frequencies, and a decrease in rolling velocity in the presence of erythrocytes. Increased fluid viscosity alone did not influence the binding frequency,and the differences could not be attributed to large near-wall excesses of the lymphocytes. The results indicate that RBCs aid in the transport and initial engagement of lymphocytes to the vascular wall, modifying the existing paradigm for immune cell surveillance of the vascular endothelium by adding the erythrocyte as an essential contributor to this process.