Selectin-mediated Leukocyte Adhesion During the Immune Response

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Selectins are cell adhesion molecules that initiate recruitment of white blood cells to targeted sites on the blood vessel wall. This process is necessary for numerous immune functions, including inflammation, lymphocyte homing, and bone marrow replenishment after transplantation. Cell recruitment proceeds via a multi-step process, with selectin-mediated rolling followed by integrin-mediated firm adhesion. This book extends current knowledge of leukocyte adhesion by examining selectin-mediated adhesion in both experimental and computational studies. Selectin-ligand interactions were experimentally characterized using a yeast display system, in which E-selectin-expressing yeast were perfused over ligand-bearing surfaces. Structure-function relationships in selectin ligands were studied using cell-free rolling experiments, in which ligand-coated microspheres were perfused over L-selectin substrate. Finally, the roles of selectins and integrins in cell adhesion were investigated using adhesive dynamic (AD) simulations. The model successfully reproduces in vivo data, and predicts synergistic functions of the two receptors in mediating leukocyte adhesion.