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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. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-01-0042v1 104/12/3774    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zennadi, R. Articles by Telen, M. J. Search for Related Content PubMed PubMed Citation Articles by Zennadi, R. Articles by Telen, M. J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Red Cells Cell Adhesion and Motility Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-v3 interactions Rahima Zennadi, Patrick C. Hines, Laura M. De Castro, Jean-Pierre Cartron, Leslie V. Parise, and Marilyn J. Telen From the Division of Hematology, Department of Medicine, Duke University Medical Center, Durham, NC; the Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC; and the Institut National de la Santé et de la Recherche Médicale Unité 76, Institut National de la Transfusion Sanguine, Paris, France. The possible role of physiologic stress hormones in enhancing adhesion of sickle erythrocytes (SS RBCs) to endothelial cells (ECs) in sickle cell disease (SCD) has not been previously explored. We have now found that up-regulation of intracellular cyclic adenosine monophosphate (cAMP)–dependent protein kinase A (PKA) by epinephrine significantly increased sickle but not normal erythrocyte adhesion to both primary and immortalized ECs. Inhibition of serine/threonine phosphatases also enhanced sickle erythrocyte adhesion at least partially through a PKA-dependent mechanism. Adhesion was mediated through LW (intercellular adhesion molecule-4 [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 counter receptor for LW was identified as the v3 integrin on ECs. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: "Stress" and sickle red cell adhesion Dhananjay K. Kaul Blood 2004 104: 3425-3426. [Full Text] [PDF] This article has been cited by other articles: R. Zennadi, A. Chien, K. Xu, M. Batchvarova, and M. J. Telen Sickle red cells induce adhesion of lymphocytes and monocytes to endothelium Blood, October 15, 2008; 112(8): 3474 - 3483. [Abstract] [Full Text] [PDF] C. Johnson and M. J. Telen Adhesion molecules and hydroxyurea in the pathophysiology of sickle cell disease Haematologica, April 1, 2008; 93(4): 481 - 485. [Full Text] [PDF] M.-H. Odievre, V. Bony, M. Benkerrou, C. Lapoumeroulie, C. Alberti, R. Ducrocq, E. Jacqz-Aigrain, J. Elion, and J.-P. Cartron Modulation of erythroid adhesion receptor expression by hydroxyurea in children with sickle cell disease Haematologica, April 1, 2008; 93(4): 502 - 510. [Abstract] [Full Text] [PDF] E. Bennett-Guerrero, T. H. Veldman, A. Doctor, M. J. Telen, T. L. Ortel, T. S. Reid, M. A. Mulherin, H. Zhu, R. D. Buck, R. M. Califf, et al. Evolution of adverse changes in stored RBCs PNAS, October 23, 2007; 104(43): 17063 - 17068. [Abstract] [Full Text] [PDF] R. Zennadi, B. J. Moeller, E. J. Whalen, M. Batchvarova, K. Xu, S. Shan, M. Delahunty, M. W. Dewhirst, and M. J. Telen Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo Blood, October 1, 2007; 110(7): 2708 - 2717. [Abstract] [Full Text] [PDF] E. M. Finnegan, G. A. Barabino, X.-d. Liu, H.-Y. Chang, A. Jonczyk, and D. K. Kaul Small-molecule cyclic {alpha}Vbeta3 antagonists inhibit sickle red cell adhesion to vascular endothelium and vasoocclusion Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H1038 - H1045. [Abstract] [Full Text] [PDF] M.-P. Wautier, W. El Nemer, P. Gane, J.-D. Rain, J.-P. Cartron, Y. Colin, C. Le Van Kim, and J.-L. Wautier Increased adhesion to endothelial cells of erythrocytes from patients with polycythemia vera is mediated by laminin {alpha}5 chain and Lu/BCAM Blood, August 1, 2007; 110(3): 894 - 901. [Abstract] [Full Text] [PDF] W. El Nemer, M.-P. Wautier, C. Rahuel, P. Gane, P. Hermand, F. Galacteros, J.-L. Wautier, J.-P. Cartron, Y. Colin, and C. Le Van Kim Endothelial Lu/BCAM glycoproteins are novel ligands for red blood cell {alpha}4{beta}1integrin: role in adhesion of sickle red blood cells to endothelial cells Blood, April 15, 2007; 109(8): 3544 - 3551. [Abstract] [Full Text] [PDF] E. Ihanus, L. M. Uotila, A. Toivanen, M. Varis, and C. G. Gahmberg Red-cell ICAM-4 is a ligand for the monocyte/macrophage integrin CD11c/CD18: characterization of the binding sites on ICAM-4 Blood, January 15, 2007; 109(2): 802 - 810. [Abstract] [Full Text] [PDF] M. J. Telen Role of Adhesion Molecules and Vascular Endothelium in the Pathogenesis of Sickle Cell Disease Hematology, January 1, 2007; 2007(1): 84 - 90. [Abstract] [Full Text] [PDF] J.-i. Nishimura, A. D. Burnette, M. Batchvarova, S. M. Nimjee, R. Zennadi, B. A. Sullenger, and M. J. Telen Blocking Adhesion of Sickle Erythrocytes to Endothelial {alpha}V{beta}3 Using RNA Aptamer. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 688 - 688. [Abstract] [Full Text] [PDF] D. K. Kaul, X.-d. Liu, X. Zhang, T. Mankelow, S. Parsons, F. Spring, X. An, N. Mohandas, D. Anstee, and J. A. Chasis Peptides based on {alpha}V-binding domains of erythrocyte ICAM-4 inhibit sickle red cell-endothelial interactions and vaso-occlusion in the microcirculation Am J Physiol Cell Physiol, November 1, 2006; 291(5): C922 - C930. [Abstract] [Full Text] [PDF] J. S. Bennett Vasoocclusion in sickle cell anemia: are platelets really involved? Arterioscler Thromb Vasc Biol, July 1, 2006; 26(7): 1415 - 1416. [Full Text] [PDF] D. K. Kaul, X.-d. Liu, X. Zhang, L. Ma, C. J. C. Hsia, and R. L. Nagel Inhibition of sickle red cell adhesion and vasoocclusion in the microcirculation by antioxidants Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H167 - H175. [Abstract] [Full Text] [PDF] E. Gauthier, C. Rahuel, M. P. Wautier, W. El Nemer, P. Gane, J. L. Wautier, J. P. Cartron, Y. Colin, and C. Le Van Kim Protein Kinase A-dependent Phosphorylation of Lutheran/Basal Cell Adhesion Molecule Glycoprotein Regulates Cell Adhesion to Laminin {alpha}5 J. Biol. 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