Activation of sickle red blood cell adhesion via integrin-associated protein/CD47-induced signal transduction.
Peripheral human red blood cells (RBCs) are not generally known to become activated and adhesive in response to cell signaling. We show, however, that soluble thrombospondin via integrin-associated protein (IAP; CD47) increases the adhesiveness of sickle RBCs (SS RBCs) by activating signal transduction in the SS RBC. This stimulated adhesion requires occupancy of IAP and shear stress and is mediated by the activation of large G proteins and tyrosine kinases. Reticulocyte-enriched RBCs derived from sickle-cell disease (SCD) patients are most responsive to IAP-induced activation. These studies therefore establish peripheral SS RBCs as signaling cells that respond to a novel synergy between IAP-induced signal transduction and shear stress, suggesting new therapeutic targets in SCD.
Brittain
J E
JE
Department of Pharmacology, School of Medicine, and. Department of Medicine, The University of North Carolina at Chapel Hill, 27599-7365, USA.
Mlinar
K J
KJ
Anderson
C S
CS
Orringer
E P
EP
Parise
L V
LV
D000755:Anemia, Sickle Cell / Q000097:blood*; D015703:Antigens, CD / Q000378:metabolism*; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004913:Erythrocytes, Abnormal / Q000502:physiology*; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D009842:Oligopeptides / Q000494:pharmacology; D019000:Phosphotyrosine / Q000378:metabolism; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology; D013312:Stress, Physiological; D019699:Thrombospondins / Q000378:metabolism / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
C120273:4N1K peptide; D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D013267:Stilbenes; D019699:Thrombospondins; D010566:Virulence Factors, Bordetella; D019000:Phosphotyrosine; C041525:3,3',4,5'-tetrahydroxystilbene; D019833:Genistein