P-selectin glycoprotein ligand-1 supports rolling on E- and P-selectin in vivo

Selectin-dependent rolling is the earliest observable event in the recruitm ent of leukocytes to inflamed tissues. Several glycoproteins decorated with sialic acid, fucose, and/or sulfate have been shown to bind the selectins, The best-characterized selectin ligand is P-selectin glycoprotein-l (PSGL- 1) that supports P-selectin-dependent rolling in vitro and in vivo. In vitr o studies have suggested that PSGL-1 may also be a ligand for E- and L-sele ctins. Introduction To study the in vivo function of PSGL-1, without the in fluence of other leukocyte proteins, the authors observed the interaction o f PSGL-1-coated microspheres in mouse venules stimulated to express P- and/ or E-selectin, Microspheres coated with functional recombinant PSGL-1 rolle d in surgically stimulated and tumor necrosis factor alpha (TNF alpha)-stim ulated mouse venules. P-selectin deficiency or inhibition abolished microsp here rolling in surgically and TNF alpha -stimulated venules, whereas E-sel ectin deficiency or inhibition increased microsphere rolling velocity in TN F alpha -stimulated venules, The results suggest that P-selectin-PSGL-1 int eraction alone is sufficient to mediate rolling in vivo and that E-selectin -PSGL-1 interaction supports slow rolling. (C) 2000 by The American Society of Hematology.