Preferential adhesion of leukocytes near bifurcations is endothelium independent

Leukocyte-endothelial interactions play central roles in many pathological conditions. However, the in vivo mechanisms responsible for nonuniform spatial distribution of adhering leukocytes to endothelial cells in microvascular networks are not clear. We used a combination of in vitro and in vivo methodologies to explain of this complex phenomenon. A mouse cremaster muscle model was used to study the spatial distribution of leukocyte-endothelial cell interaction in vivo. A PDMS-based synthetic microvascular network (SMN) device was used to study interactions of functionalized microspheres using a receptor-ligand system in a (endothelial) cell-free environment for the in vitro studies. Our in vivo and in vitro findings indicate that both leukocytes in vivo and microspheres in vitro preferentially adhere near bifurcation (within 1-2 diameters from the bifurcation). This adhesion pattern was found to be independent of the diameter of the vessels. These findings support our hypothesis that the fluidic patterns near bifurcations/junctions, and not the presence or cellular aspects of the system (e.g. cell deformation, cell signaling, heterogeneous distribution of adhesion molecules), is the main controlling factor behind the preferential adhesion patterns of leukocytes near bifurcations.