Shedding of selectin and immunoglobulin superfamily adhesion molecules and its functional implications. For simplification, only one example receptor ligand pair (very late antigen-4 (VLA-4)/vascular cell adhesion molecule-1 (VCAM-1)) is illustrated. (A) Interactions of cell surface integrin VLA-4, present on leukocytes, with endothelial cell surface VCAM-1 during different steps in the leukocyte adhesion cascade. (B) Ectodomain shedding of cell surface VCAM-1 (thereby generating the soluble isoform sVCAM-1) by sheddases might reduce leukocyte adhesion to the endothelium on two complementary levels: reduction of cell surface density of adhesion molecules (for example, decreased endothelial cell surface VCAM-1, in this example); and binding of the resulting soluble isoforms to cell surface ligands (that is, binding of sVCAM-1 to leukocyte cell surface VLA-4 in this example), thereby serving as competitive antagonists (or decoy ligands) for the remaining cell-surface adhesion receptors. See  and the text for more details on functional implications of shedding.