REGULATION OF LEUKOCYTE MIGRATION BY ACTIVATION OF THE LEUKOCYTE ADHESION MOLECULE-1 (LAM-1) SELECTIN

A CENTRAL feature of host defence is the ability of leukocytes to enter tissues in response to immune or inflammatory stimuli. The leukocyte adhesion molecule-1 (LAM-1) regulates the migration of human leukocytes by mediating the binding both of lymphocytes to high endothelial venules of peripheral lymph nodes and of neutrophils to endothelium at inflammatory sites 1-10. As lymphocytes and neutrophils express the same LAM-1 protein 11,12, it is not clear how lineage-specific differences in leukocyte migration are controlled. We now report that the affinity of LAM-1 for a carbohydrate-based ligand, PPME 13-16, is dramatically increased following lymphocyte and neutrophil activation by lineage-specific stimuli. In addition, activation of lymphocytes by physiological stimuli enhanced LAM-1-dependent binding to high endothelial venules. Thus, transient changes in LAM-1 affinity after leukocyte stimulation probably directly influence leukocyte migration.