We have characterized the two-dimensional spatial dependence of the hydrodynamic interactions between two adhesively rolling leukocytes in a live venule in the mouse cremaster muscle. Two rolling leukocytes were observed to slow each other down when rolling together in close proximity due to mutual sheltering from the external blood flow in the vessel lumen. A previous study of leukocyte rolling interactions using carbohydrate-coated beads in a parallel-plate flow chamber and a detailed computer model of adhesion in a multicellular environment is in qualitative agreement with the current in vivo results.The slow rolling motion of leukocytes ͑white blood cells͒ along the vessel wall in postcapillary venules is a necessary step in the cellular immune reponse. 1 The dynamics of leukocyte rolling, as controlled by the kinetics of selectincarbohydrate bond dissociation and other factors, has been mostly studied in flow chamber systems at very dilute concentrations of cells. 2 Such studies have been useful in determining how cell size and shear rate influence adhesion. 3 However, in vivo, leukocyte adhesion with the vessel wall occurs in the presence of a dense suspension of blood cells. The effects of the surrounding suspension of cells on leukocyte adhesion to the endothelium have not been fully elucidated. In previous studies we have begun to determine these effects by formulating a computational model of cell-surface interactions under flow in a multicellular environment that fuses a stochastic simulation of receptor-ligand binding with a rigorous boundary elements calculation of suspension flow at zero Reynolds number. 4 The multiparticle adhesive dynamics ͑MAD͒ simulation agrees quite well with flow chamber experiments using carbohydrate-coated beads rolling on a purified P-selectin surface. 4-6 One of the main results of this work has been to demonstrate that a leukocyte will roll at a lower velocity when in close proximity to another rolling leukocyte. Reference 4 shows the spatial dependence of this effect in both the flow x and transverse y directions, since in the flow chamber experiments the entire substrate surface is viewed from below. Recently, we have shown that some of these hydrodynamic effects may be observed in live hamster microvessels. 7 By taking midplane cross sections of straight, unbranched vessels to produce a side view of leukocyte-wall interactions, we were able to show a correlation between leukocyte rolling velocity and the distance between rolling leukocytes in the flow direction only. A decrease in rolling velocity with decreasing cell-cell separation was observed, thus, previous microsphere experiments, computational results, and a 1 / r hydrodynamic scaling are all in qualitative agreement with this latest animal study.Several recent fluid mechanical studies have examined the interaction of small particles with a planar wall, 8-13 however, none of these have focused on the adhesive rolling motion of spheres along the wall of a circular tube. In our system, characteristic Reynolds numb...
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