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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3774-3781.
Prepublished online as a Blood First Edition Paper on August 12, 2004; DOI 10.1182/blood-2004-01-0042.
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Submitted January 21, 2004
Accepted May 26, 2004
Epinephrine Acts Via Erythroid Signaling Pathways to Activate Sickle Cell Adhesion to Endothelium Via LW- v 3 Interactions
Rahima Zennadi, Patrick C Hines, Laura M De Castro, Jean-Pierre Cartron, Leslie V Parise, and Marilyn J Telen*
Division of Hematology, Department of Medicine, Duke University Medical Center, Durham, NC, USA
Department of Pharmacology, University of North Carolina, Chapel Hill, NC, USA
Institut National de la Transfusion Sanguine, Institut National de la Sante et de la Recherche Medicale Unite 76, Paris, France
* Corresponding author; email: telen002{at}mc.duke.edu.
The possible role of physiological stress hormones in enhancing adhesion of sickle erythrocytes (SS RBC) to endothelial cells (EC) in sickle cell disease (SCD) has not been previously explored. We have now found that upregulation of intracellular cAMP-dependent protein kinase A (PKA) by epinephrine significantly increased sickle but not normal erythrocyte adhesion to both primary and immortalized EC. Inhibition of serine/threonine phosphatases also enhanced sickle erythrocyte adhesion at least partially through a PKA-dependent mechanism. Adhesion was mediated through LW (ICAM-4, CD242) blood group glycoprotein, and immunoprecipitation studies showed that LW on sickle but not on normal erythrocytes undergoes increased PKA-dependent serine phosphorylation as a result of activation. The major counterreceptor for LW was identified as the v 3 integrin on EC. These data suggest that adrenergic hormones such as epinephrine may initiate or exacerbate vaso-occlusion and thus contribute to the association of vaso-occlusive events with physiologic stress.

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