GLYCOLIPID LIGANDS FOR SELECTINS SUPPORT LEUKOCYTE TETHERING AND ROLLING UNDER PHYSIOLOGICAL FLOW CONDITIONS

Selectin interactions with glycolipids have been examined previously u nder static conditions, whereas physiologic interactions mediated by s electins take place under flow. We find that under physiologic flow co nditions, sialyl Lewis(x) (sLe(x)) glycolipid and sialyl Lewis(a) (sLe (a)) neoglycolipid support tethering and rolling adhesions of Chinese hamster ovary (CHO) cells expressing E-selectin and lymphoid and myelo id cells expressing L-selectin. These selectin-mediated adhesions pers ist at the highest shear stresses that occur in postcapillary venules in vivo and occur at lower site densities than found for sLe(x) on neu trophils. The interactions are Ca2+-dependent and can be specifically and completely blocked with anti-selectin mAbs. Asialo nonfucosylated glycolipids are inactive, and sulfatide supports weak tethering, but n ot rolling, of L-selectin-expressing cells. Rolling velocities and res istance to detachment are related to the glycolipid site density and f all within the range measured for neutrophil and myeloid cell rolling on substrates containing purified selectins. These observations are th e first indication that glycolipids can interact with selectins in phy siologic flow conditions, and can contribute to rolling adhesions.