alexa Activation of sickle red blood cell adhesion via integrin-associated protein CD47-induced signal transduction.
Haematology

Haematology

Journal of Blood Disorders & Transfusion

Author(s): Brittain JE, Mlinar KJ, Anderson CS, Orringer EP, Parise LV, Brittain JE, Mlinar KJ, Anderson CS, Orringer EP, Parise LV

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Abstract 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.
This article was published in J Clin Invest and referenced in Journal of Blood Disorders & Transfusion

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