Adhesive interactions involving SS RBCs. (A) Multiple interactions between SS RBCs and endothelial cells, extracellular matrix, and plasma proteins. Red cells express multiple adhesion molecules that recognize ligands on either plasma protein “bridging molecules” or endothelial cell surfaces. Specific adhesion receptors on red cells that contribute to vaso-occlusion include ICAM-4 (the LW blood group protein, a receptor for several integrins), BCAM/Lu (the Lutheran blood group protein, a receptor for laminins (LAM) containing the α5 chain [laminins-10 and -11]), and CD44 (which bears the Indian blood group antigens), which is involved in binding to fibronectin and E-selectin. SA, sialic acid; FBN, fibronectin; TSP, thrombospondin; ULvWF, ultra-large von Willebrand factor. (B) Interactions between SS RBCs and leukocytes adherent to vessel walls. Many stimuli may activate leukocyte adhesion, including cytokines and contact with SS RBCs. Adhesion to endothelial cells initially occurs via selectins expressed by endothelial cells but ultimately likely also involves endothelial integrins. ESL-1, E-selectin ligand-1; PSGL-1, P-selectin glycoprotein ligand-1.