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 wall is believed to contribute to the vascular occlusion observed in patients with sickle call 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 these patients suggests that exposed extracellular matrix proteins could provide a potential substrate for sickle RBC adhesion. To determine whether RBC adhesion receptors could mediate adhesion to extracellular matrix proteins, we tested their ability to adhere to a variety of immobilized, purified proteins under flow conditions. Neither sickle nor normal RBC adhered to fibronectin, vitronectin, fibrinogen, or collagen. In contrast, we observed substantial adhesion of sickle but not normal RBC to thrombospondin (TSP). The adhesion was not inhibited with known antagonists of the GPIV-TSP interaction, nor by inhibitors of several other known binding domains in TSP. Moreover, the adhesion was resistant to inhibition by soluble TSP, suggesting that immobilization of TSP exposes an adhesive site that is cryptic on TSP in solution. However, the glycosaminoglycans, chondroitin sulfate A, and dextran sulfate 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.
Joneckis
C C
CC
Department of Pharmacology, The University of North Carolina at Chapel Hill 27599-7365, USA.
Shock
D D
DD
Cunningham
M L
ML
Orringer
E P
EP
Parise
L V
LV
D053674:Aggrecans; D000595:Amino Acid Sequence; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018955:CD36 Antigens / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004913:Erythrocytes, Abnormal / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology; D037181:Lectins, C-Type; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011509:Proteoglycans / Q000276:immunology / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D012212:Rheology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019699:Thrombospondins; D014407:Tumor Cells, Cultured; D019096:Vitronectin / Q000378:metabolism
D053674:Aggrecans; D000911:Antibodies, Monoclonal; D018955:CD36 Antigens; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D016201:Receptors, Lymphocyte Homing; D019699:Thrombospondins; D019096:Vitronectin; D003094:Collagen; D013755:Tetradecanoylphorbol Acetate