GLYCOPROTEIN IV-INDEPENDENT ADHESION OF SICKLE RED-BLOOD-CELLS TO IMMOBILIZED THROMBOSPONDIN UNDER FLOW CONDITIONS

The abnormal adherence of red blood cells (RBC) to the blood vessel wa ll is believed to contribute to the vascular occlusion observed in pat ients with sickle cell anemia. The cell adhesion receptors GPIV (CD36) and integrin alpha(4) beta(1) (CD49d/CD29) were previously identified on circulating sickle reticulocytes, and shown to mediate sickle RBC adhesion to the endothelium. The presence of damaged endothelium in th ese patients suggests that exposed extracellular matrix proteins could provide a potential substrate for sickle RBC adhesion, To determine w hether RBC adhesion receptors could mediate adhesion to extracellular matrix proteins, we tested their ability to adhere to a variety of imm obilized, purified proteins under flow conditions. Neither sickle nor normal RBC adhered to fibronectin, vitronectin, fibrinogen, or collage n, In contrast, we observed substantial adhesion of sickle but not nor mal RBC to thrombospondin (TSP). The adhesion was not inhibited with k nown antagonists of the GPIV-TSP interaction, nor by inhibitors of sev eral other known binding domains in TSP, Moreover, the adhesion was re sistant to inhibition by soluble TSP, suggesting that immobilization o f TSP exposes an adhesive site that is cryptic on TSP in solution, How ever, the glycosaminoglycans, chondroitin sulfate A, and dextran sulfa te were potent inhibitors of this adhesion, These results suggest that a mechanism distinct from GPIV is responsible for sickle RBC adhesion to immobilized TSP under flow conditions. (C) 1996 by The American So ciety of Hematology.