Leukocytes rolling and recruitment by endothelial cells: hemorheological experiments and numerical simulations

The recruitment of leukocytes from the blood stream and their subsequent adhesion to endothelial walls are essential stages to the immune response system during inflammation. The precise dynamic mechanisms by which molecular mediators facilitate leukocyte arrests are still unknown. In this study combined experimental results and computer simulations are used to investigate localized hydrodynamics of individual and collective behavior of clusters of leukocytes. Leukocyte-endothelial cell interactions in post-capillary venules of Wistar rats cremaster muscle were monitored by intravital microscopy. From these experiments the hemorheologic and hemodynamical measured parameters were used in time dependent three-dimensional computer simulations, using a mesoscopic lattice Boltzmann flow solver for shear thinning fluids. The dynamics of leukocyte clusters under generalized Newtonian blood flow with shear thinning viscosity was computed and discussed. In this paper we present quantified distributions of velocity and shear stress on the surface of leukocytes and near vessel wall attachment points. We have observed one region of maximum shear stress and two regions of minimum shear stress on the surface of leukocytes close to the endothelial wall. We verified that the collective hydrodynamic behavior of the cluster of recruited leukocytes establishes a strong motive for additional leukocyte recruitment. It was found that the lattice Boltzmann solver used here is fully adaptive to the measured experimental parameters. This study suggests that the influence of the leukocytes rolling on the increase of the endothelial wall shear stress may support the activation of more signalling mediators during inflammation.