A computational study of the effects of adherent leukocytes on secondary recruitment

Leukocyte rolling is known to be mediated by the selectin family of adhesion molecules and their corresponding ligands and is characterized by the formation and breakage of receptor-ligand bonds. Selectin mediated rolling is associated with the initial stages of the leukocyte adhesion cascade (LAC) in which the cell passes through several stages including chemo-attraction, rolling adhesion, tight adhesion and transmigration before moving out of the circulatory system towards the site of injury. This thesis studies the initial stages of the leukocyte adhesion cascade through a direct numerical simulation based on boundary element techniques. Besides, cell deformation during rolling is believed to further enhance rolling interactions. This feature is accounted for by implementing a constitutive model that qualitatively represents the morphology of white blood cells in the early stages of selectin mediated rolling. This research describes the contribution of contact mechanics towards modulation in the contact area for cell substrate interactions. The results predict that compliant cells could roll slower (~ 25%) as compared to their stiffer counterparts. The effect of variations in cell size and bond compression on the decrease in the translational velocity as well as the inherent noisiness in the translational velocity is investigated.;The latter part of this thesis attempts to quantify hydrodynamic recruitment of leukocytes with a view to providing insights into cell trafficking in physiological phenomena such as the homing of stem cells towards bone marrow. In vivo experimental data of leukocyte accumulations during exposure to Zymosan-Activated Serum (ZAS) in rabbits and immune response in hamster cheek pouches appears to reinforce this hypothesis. The influence of deformation on the attachment of free-stream cells through collisions and near wall interactions with adherent cells is numerically investigated. The trajectories of free-stream cells colliding with deformed adherent cells are computed through a series of glancing collisions in order to study the influence of cell shape on secondary recruitment.