Effects of complex vessel geometries on neutrophil margination and adhesion in post-capillary venules.

摘要

The inflammatory process is a regular occurrence within a healthy body. As part of the inflammatory process, leukocytes flow through blood vessels and are recruited to the region of the injury. Neutrophils play a significant role in this process; however the margination of neutrophils to particular locations in micro vessels is not fully understood. Post capillary venules, in particular, have complex geometries which may contribute to non-uniform adhesion of neutrophils. Margination is a phenomenon that occurs during the relatively early phases of inflammation; as a result of dilation of capillaries and slowing of the bloodstream, leukocytes tend to occupy the periphery of the cross-sectional lumen. Other investigations have looked at the adhesion of neutrophils in vivo or flow patterns in converging tubes, but the correlation between flow patterns in complex geometries and neutrophil margination is not well understood. This study seeks to investigate correlations between margination and bulk flow patterns as well as parameters that affect bulk flow properties. The primary aim of this investigation is to create specific computational and in vitro models based on in vivo data that isolate the hydrodynamic mechanisms associated with complex geometries. Main geometric factors that were investigated were surface roughness, branch geometries, number of convergences and squared vs. rounded t-junctions. To determine the effect of surface roughness a large scale parallel plate flow chamber model as well as a microfabrication technique to simulate roughness at the blood vessel scale were created that simulate surface roughness due to endothelial cell nuclei. CFD modeling was also used to determine effects of other geometric factors including branch geometries, number of convergences and squared vs. rounded t-junctions. Overall, results from this study suggest that complex geometries can have a significant role on neutrophil margination and adhesion in blood vessels. A preliminary relationship between wall shear stress and margination was established.