Selectin-mediated Leukocyte Adhesion During the Immune Response: Experimental and Computational Studies of White Blood Cell Recruitment to the Vascular Wall

Selectins are cell adhesion molecules that initiaterecruitment of white blood cells to targeted sites onthe blood vessel wall. This process is necessary fornumerous immune functions, including inflammation, lymphocyte homing, and bone marrow replenishmentafter transplantation. Cell recruitment proceeds viaa multi-step process, with selectin-mediated rollingfollowed by integrin-mediated firm adhesion. Thisbook extends current knowledge of leukocyte adhesionby examining selectin-mediated adhesion in bothexperimental and computational studies. Selectin-ligand interactions were experimentallycharacterized using a yeast display system, in whichE-selectin-expressing yeast were perfused overligand-bearing surfaces. Structure-functionrelationships in selectin ligands were studied usingcell-free rolling experiments, in which ligand-coatedmicrospheres were perfused over L-selectin substrate. Finally, the roles of selectins and integrins in celladhesion were investigated using adhesive dynamic(AD) simulations. The model successfully reproducesin vivo data, and predicts synergistic functions ofthe two receptors in mediating leukocyte adhesion.